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Items in House, Senate and Conference Appropriations Committee Reports


 

FY 2001 House Appropriations Committee Report Lauguage (H.Rpt. 106-645)

 

Item: Alzheimer's Disease

NINDS recently issued two program announcements aimed at increasing the number of clinical trials for Alzheimer's disease. The Committee encourages the Institute to continue to assign this a high priority and to continue its close working relationship with NIA, NIMH, and NINR.

Action taken or to be taken
For many years, NINDS has supported research in many areas of Alzheimer's Disease, and the Institute is encouraged by recent developments in understanding the cellular and genetic basis of this disorder. In an effort to move preclinical findings to human testing as efficiently as possible, the Institute, along with the NIMH and NIA, issued two joint Program Announcements (PAs) encouraging the submission of Alzheimer's Disease Pilot Clinical Trial Planning Grants and Clinical Trial grant applications in early 1999. The ultimate effect of these program activities will not be known for some time, but the goal of these PAs is to enhance the development of clinical trials of pharmacological therapies for the cognitive and behavioral symptoms of Alzheimer's Disease. In addition, NINDS has undergone a recent reorganization which will enable the Institute to place a greater emphasis on Alzheimer's activities from a programmatic and planning perspective. At present, two of the Institute's seven new areas of research emphasis are Neurodegeneration and Clinical Trials. The development of a Neurodegeneration focus will enable staff to better coordinate Alzheimer's research activities with those of other degenerative diseases, such that research output is maximized in all areas. In addition, the focus on Clinical Trials has been designed to stimulate the numbers of clinical studies funded by the Institute, and to facilitate the planning and monitoring of these trials. It is anticipated that the area of neurodegenerative disease, including Alzheimer's, may derive significant benefit from this new effort. Lastly, NINDS will also coordinate its research activities in Alzheimer's Disease with all other ICs working in this field, including NIA and its Alzheimer's Disease Center Program, as well as NIMH and NINR.

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Item: Amyotrophic lateral sclerosis

NINDS is encouraged to build on these initiatives to stimulate investigator-initiated proposals. The Committee also encourages NINDS to enhance its research for treatment and cure of ALS.

Action taken or to be taken
In March of 2000 NIH issued a request for applications soliciting proposals for research on amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, and other diseases that affect motor neurons. The response of the scientific community to that solicitation has been very encouraging, and review of the research proposals is underway. In April 2000 NINDS, working together with private organizations, held a workshop that brought together scientists from academia, industry and government to review current knowledge about what causes nerve cells to degenerate in these diseases, to discuss what we need to know to develop cures, and to consider the prospects for applying "high-throughput screening" technology to develop drugs to this end. High throughput screening uses robotics and miniaturized testing to rapidly screen large numbers of chemicals to find leads for drug development. Industry is less likely to apply this approach to relatively low prevalence disorders such as ALS. NINDS will continue its efforts to enhance research to find a cure for ALS, including programs in preparation that will help make high-throughput screening technology accessible to ALS researchers. NINDS also is intensifying its efforts in gene therapy, the biology of neurotrophic factors, and several other areas that hold promise for ALS and other neurodegenerative disorders.

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Item: Batten's disease

The Committee is pleased with the progress that has been made with regards to both the infantile and juvenile forms of Batten's disease and encourages NINDS to continue to focus on Batten's disease research through all available mechanisms, as appropriate, including the study of gene therapy treatment for the late infantile form of the disease.

Action taken or to be taken
NINDS continues its long-term efforts to find cures for all forms of Batten disease. In April 1999 the Institute, working together with the Children's Brain Disease Foundation and the NIH Office of Rare Diseases, held a workshop to explore new directions for Batten disease research, and in June 1999 the Institute helped support an international conference on this disease. As part of its continuing efforts against Batten disease the Institute also hosted two additional workshops, one with a more global focus in November 1999 and another more focused on the genes CLN1 and CLN2 in May 2000. In July 2000 the Institute issued a program announcement to encourage scientists to apply progress in fundamental neuroscience to pediatric brain disorders. Through that program NINDS has funded new exploratory grants focusing on Batten disease. In addition to research targeted specifically to Batten disease, the Institute continues its broad efforts to overcome the common obstacles to gene therapy for all brain diseases, including a workshop on gene therapy for nervous system diseases held in October 2000.

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Item: Dystonia

The Committee also encourages NINDS to enhance its collaboration with the dystonia research community in supporting epidemiological studies on dystonia and enhancing public and professional awareness of this disorder.

Action taken or to be taken
NINDS continues to support extramural and intramural research on the dystonias, including new and continuing grants. The broad program of research ranges from fundamental neuroscience studies that lay the groundwork for understanding what goes wrong with brain circuits in dystonia, through clinical studies in patients, to clinical trials of treatments. The Institute, working with private groups, is also sponsoring workshops on critical aspects of dystonia research, including a November 2000 international conference held on blepharospasm (a common form of dystonia that has not received much attention from researchers), a January 2001 meeting "From genes to function in dystonia," and a three day "Dystonia International Symposium" in September 2001. The NINDS Intramural program, which has long maintained an active research program on the dystonias, is enhancing its efforts to bring in and train fellows in dystonia research. The Institute has also updated its public information on dystonia and has redesigned its web site to make this and other information more accessible.

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Item: Epilepsy

The Committee is pleased that the Institute sponsored a conference in March 2000 on "Curing Epilepsy: Focus on the Future." NINDS is encouraged to enhance research to address research issues related to the impact of seizures on young children, women, the elderly and those with intractable or uncontrolled epilepsy. NINDS is also encouraged to develop research plans and goals for the anti-epileptic drug development program and to expand its research efforts in the prevention, treatment, and eventual cure of epilepsy. The Director should be prepared to testify on its efforts to advance these areas of research at the fiscal year 2002 appropriations hearing.

Action taken or to be taken
NINDS is committed to both understanding the causes of and developing therapies for all forms of epilepsy, and the research the Institute conducts has broad implications for our understanding of this disease. Many of the epilepsy projects that NINDS supports also have direct relevance to our understanding of seizure development in women, children, the elderly, and those individuals with intractable forms of the disease. As an example, NINDS is funding several projects involving childhood epilepsy, including studies of the behavioral effects of epilepsy, and the development of fever-related seizures. In order to improve our understanding of epilepsy in women, the Institute is supporting several studies of the relationship of hormonal fluctuations in females to epileptic changes in the brain, including two pilot clinical trials. Other NINDS-supported work is focused on understanding how surgical treatment of epilepsy affects the brain as it ages. Knowledge gained from this type of project may have implications for individuals who have managed their epilepsy for many decades.

As part of its Epilepsy Therapeutics Research Program (formerly the Antiepileptic Drug Development Program), NINDS has screened over 21,000 compounds for specific anti-epileptic and central nervous system effects in the past 25 years. As a result, approximately 20 drugs have been evaluated in clinical trials, with five ultimately being made available for widespread clinical use in treating epilepsy. Several others are currently under clinical investigation. At present, the Program is in the process of recruiting staff and expects to continue the emphasis on the search for new anti-epileptic agents while expanding screening activities for other neurological diseases.

In addition to these activities, NINDS planning in the area of epilepsy research was stimulated by the successful White House-initiated conference, entitled "Curing Epilepsy: Focus on the Future," held by NINDS in March 2000. This conference, a highly successful effort that brought together clinicians, basic scientists, and members of the epilepsy patient and advocacy community, was the starting point of a focused NINDS planning effort on epilepsy. This meeting was remarkably successful in bringing together a number of junior researchers, to stimulate their interest in epilepsy research. To build on this success, a new Request for Applications (RFA), entitled "Innovation in Translational Epilepsy Research for Junior Investigators," was announced at the meeting. The goal of this RFA is to stimulate collaboration among junior researchers with expertise in fields such as clinical research, imaging techniques, and drug therapies, in order to bring their experience to bear in translating basic science research findings into treatments for epileptic conditions. Applications have been received and will be reviewed in March 2001. Another important outcome of the meeting was the development of a series of challenging but encouraging benchmarks by Institute staff and prominent epilepsy researchers. These benchmarks will be used to help investigators in the field of epilepsy research maximize their research efforts towards the translation of basic science research findings into improved clinical therapies that will prove a true "cure"- defined as "no seizures, no side effects" - for this disease. Several additional meetings are currently being planned in follow-up to the White House conference, including conferences on monotherapy, and the use of animal models in epilepsy research.

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Item: Familial Dysautonomia

Familial Dysautonomia (FD) is a genetic disease that affects individuals of Eastern European Jewish ancestry, and primarily causes dysfunction of the autonomic and sensory nervous systems. Children with FD often are unable to regulate their blood pressure or body temperature, swallow or digest food normally, or respond to physical stress. The Committee encourages NINDS to study this disease in order to improve the quality of FD sufferers and enable more children to reach adulthood.

Action taken or to be taken
Familial Dysautonomia (FD) refers to a genetic disorder of the autonomic (independent of conscious thought) and sensory nervous systems. The hallmark of dysautonomias, such as FD, is dysfunctional regulation of autonomic processes such as digestion, blood pressure, heart rate, and body temperature. The NINDS supports and conducts research on dysautonomias including FD. Research efforts have led to the development of prenatal diagnostic testing for FD using linked genetic markers. Recent investigations of the genetics of FD have precisely mapped the gene responsible for FD to a specific region of human chromosome 9. Efforts are currently under way to identify this FD gene, and determine its normal function. Research supported by NINDS aims to discover ways to improve diagnosis and treatment, and, ultimately, to prevent this devastating disorder.

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Item: Fragile X

The Committee urges NINDS to enhance its research activities on Fragile X and to include Fragile X patients in its studies of related disorders. The Committee also urges NINDS to coordinate these efforts with other Institutes working on related activities, including NIMH and NICHD.

Action taken or to be taken
Trinucleotide repeat expansion of at least three genes located on the X chromosome has been associated with the formation of "fragile sites." Fragile X syndrome is one of several diseases linked to trinucleotide repeat mutations in different genes. The other diseases are Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia type 1 (SCA1), X-linked spinobulbar muscular atrophy (Kennedy's disease), dentatorubral and pallidoluysian atrophy (DRPLA), spinocerebellar ataxia type 3 (SCA3 or Machado-Joseph disease), and myotonic dystrophy.

NINDS supports research on the range of neurological disorders linked to trinucleotide repeat mutations, and specifically on the functions of the Fragile X protein, FMRP, in neurodevelopment and in the development of seizures. In addition, Fragile X and several other trinucleotide repeat disorders are specifically identified in a Program Announcement issued by the NINDS, in conjunction with the National Institute of Child Health Human Development (NICHD) and the National Institute of Mental Health (NIMH), to invite exploratory research grant applications to facilitate the translation of fundamental neurobiology to the study of pediatric brain disorders. There are a number of topics of common interest in Fragile X syndrome that warrant further discussion with NIMH and NICHD following the conference, "FMRP: What Does it Do?" These include RNA binding properties of FMRP, regulation of FMR1 and the other proteins with which FMRP interacts, the subcellular distribution of FMRP, and the links between FMRP function over development and the fragile X phenotype. NINDS looks forward to identifying additional topics of mutual interest as NIMH actively works with NICHD to support similar conferences in the future.

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Item: Hyperbaric Oxygen Therapy

The Committee understands that hyperbaric oxygen therapy on coma patients showed the greatest reduction in mortality of any treatment for coma. NINDS is encouraged to collaborate with NIMH and the Centers for Disease Control and Prevention to research the use of this therapy for both stroke and brain injury patients.

Action taken or to be taken
There has been periodic interest in hyperbaric oxygen therapy for stroke since the 1960s, but no clear benefit has been shown. Several clinical studies performed in 1991, 1995 and in 1999 concluded that treating stroke patients with hyperbaric oxygen did not produce dramatic improvement in acute stroke patients. Moreover, the treatment was reported to be poorly tolerated, and the overall survival rate was statistically equal in patients who did not receive hyperbaric oxygen compared to those who did.

The results of a study of hyperbaric oxygen for traumatic brain injury were published in 1992 showing some reduction of mortality, but with significant persistence of neurological deficits. (J. Neurosurgery 1992, June: 76 (6): 929-34) The Institute would welcome the opportunity to support new hyperbaric oxygen studies if judged scientifically meritorious.

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Item: Neurofibromatosis

Recent advances in Neurofibromatosis (NF) research have linked NF to cancer, brain tumors, learning disabilities, and heart disease. The Committee encourages NINDS to strengthen its NF basic and clinical research portfolio through all available mechanisms, as appropriate, including clinical trials. The Committee urges the Institute to continue to coordinate its efforts with other Institutes engaged in NF research and be prepared to report on the status of the NF research portfolio at its fiscal year 2002 appropriations hearing.

Action taken or to be taken
The NINDS supports a range of research directed at and related to the neurofibromatoses - from the genetics of NF1 and NF2 to the neurological dysfunctions, both cognitive and behavioral - associated with NF1. Several other NIH institutes also have an interest in NF research: the National Cancer Institute (NCI) has a significant investment in research on tumor suppressor genes and the tumors and malignancies associated with NF; the National Institute on Deafness and Other Communication Disorders (NIDCD) on taste and hearing impairments associated with acoustic neuromas; the National Eye Institute (NEI) on the role of the NF2 gene in cataract formation; the National Institute of Child Health and Human Development (NICHD) on learning disabilities; and the National Heart, Lung, and Blood Institute (NHLBI) on the NF1 gene and cardiac development.

The neurofibromatoses represent a remarkable opportunity for basic and clinical researchers. The isolation of the NF1 and NF2 genes, preliminary discoveries regarding their function, the development of animal models, and other advances have begun to provide the tools for the ultimate development of novel therapeutic approaches. To capitalize on this opportunity, the NINDS hosted a two-day workshop to assess the status of NF research and to identify future research opportunities to be developed in FY2001. In addition to a panel of 17 extramural basic scientists and clinicians, the meeting included representatives from the other five NIH institutes (NCI, NICHD, NEI, NHLBI, and NIDCD), two other federal agencies with NF research programs (the Department of Defense and the Veterans Administration), the pharmaceutical industry, and two national NF patient advocacy groups. The meeting explored recent basic science and therapeutics research, and discussed proposals regarding research priorities and strategies in NF. Several priorities were agreed upon, including development of more refined animal models for NF1 and NF2; further analysis of the mechanisms of action of neurofibromin and merlin - the proteins whose functions are disrupted in NF1 and NF2 respectively; and the identification of modifier genes that affect the expression of neurofibromin and merlin. The results of this workshop were subsequently discussed with the broader NF research community at the annual meeting of the International Consortium for the Molecular and Cell Biology of NF1 and NF2. The NINDS is working on developing several new NF- related activities to respond to the research needs and priorities identified through these meetings, and to stimulate interest in NF research from researchers in other fields. These activities will likely be focused on gene discovery research directly applicable to finding modifier genes for NF, and development of a registry for neurological disorders which would include a DNA collection and facilitate natural history and genetic studies in NF. These activities will employ a variety of mechanisms - RFA, RFP, and investigator-initiated projects, as well as an additional workshop to facilitate NF clinical research.

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Item: Parkinson's Disease

The Committee is encouraged by continuing discoveries in the cause, pathophysiology, and treatment of Parkinson's disease, and continues to encourage NINDS to enhance efforts to speed the development of effective therapies for this devastating disorder.

The Committee also recognizes the benefits of research breakthroughs in this area on other disorders within the Institute's scope. The Committee is further aware that the NIH has completed a Parkinson's-focused research agenda including professional judgement funding projections for the next five years. The Committee urges NINDS to enhance its funding levels for Parkinson's-focused research to implement the agenda's recommendations. The Committee also urges NINDS to collaborate with the Agency for Healthcare Research and Quality, the Centers for Disease Control and Prevention, and private sector foundations to expand research to provide the groundwork of information and intervention strategies for surveillance and control of suffering and disability associated with the disease.

Action taken or to be taken
NINDS is committed to a broad-based approach to understanding and treating Parkinson's Disease through the continued development of both intramural and extramural research activities.

In January 2000, NIH held a Parkinson's Disease planning conference in response to a Congressional request to develop a long-term research agenda in this area. This conference included NIH staff, researchers, clinicians, and advocacy group representatives. Based on the recommendations from this meeting, NINDS, along with several other institutes, developed a five-year plan for research on Parkinson's, which was released in March 2000. This plan outlines a number of aggressive strategies that the NIH will utilize in enhancing research progress in this area. Specific targets for further exploration that are identified in this plan include the risk factors and underlying causes of the disease, the genetic and cellular causes of cell death, changes to neuronal circuitry, pharmacological and surgical approaches to treatment, gene therapy treatment approaches, advances in genetic technology, new animal models, improvements in imaging techniques, high throughput drug screening, and the establishment of repositories for affected brain tissue.

NINDS has developed a Parkinson's Disease Implementation Committee that includes Institute staff, extramural researchers, and members of the advocacy community. This Committee, which has held two meetings since March, will monitor the progress that the Institute makes on its Parkinson's planning effort, and suggest new directions for implementation. NINDS has taken several actions to make progress on the plan as rapidly as possible. In March 2000, a meeting of representatives of the 11 currently funded Morris K. Udall Parkinson's Disease Research Centers of Excellence was held, with the overall goal being to discuss research being conducted at each center and to coordinate ongoing and future collaborations. NINDS has awarded supplements to Udall centers for critical projects such as expediting drug discovery, identifying Parkinson's genes, and investigating Parkinson's disease in minority populations. Other program actions have also been taken, including publication of a Request for Applications (RFA) on Parkin, a protein implicated in the early-onset forms of Parkinson's. Several projects were funded from an RFA on Deep Brain Stimulation, a novel therapy that holds promise for providing effective symptomatic treatment for some Parkinson's patients, and a follow-up RFA will focus on other aspects of this form of therapy. In addition, Parkinson's Disease was a highlight of two recent meetings sponsored by the Institute, the first a workshop on Gene Therapy, and the second a meeting of the Therapeutic Opportunities in Parkinson's Disease Working Group, both held in October 2000. The latter workshop was designed to help focus a solicitation on Parkinson's therapies that the Institute plans to issue. Lastly, NINDS is very interested in improving surveillance efforts related to Parkinson's, and has already initiated discussions with the Centers for Disease Control and Prevention to this end. Efforts will be made to include other federal agencies, such as the Agency for Healthcare Research and Quality, and the advocacy community in this project as it is developed.

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Item: Reflex Sympathetic Dystrophy

Reflex Sympathetic Dystrophy (RSD), also known as Complex Regional Pain Syndrome (CRPS), is a chronic debilitating condition characterized by severe burning pain, pathological changes in bone and skin, excessive sweating, tissue swelling, and extreme sensitivity to touch. It is estimated that between two and five percent of individuals with peripheral nerve injury and up to 20 percent of those with paralysis on one side of the body will suffer from RSD. The Committee encourages NINDS, together with other relevant Institutes, to enhance research in this area through all available mechanisms, as appropriate, including a State of the Science meeting.

Action taken or to be taken
The NINDS supports a large and varied portfolio of pain research, including research on chronic pain conditions such as Reflex Sympathetic Dystrophy (RSD, also known as Complex Regional Pain Syndrome (CRPS). This includes studies aimed at both understanding the basic mechanisms of pain and at developing more effective treatments for relieving pain. Together with National Institute of Dental and Craniofacial Research, NINDS leads the NIH Pain Consortium, which was established in 1997 to encourage information sharing and collaborative research efforts, provide coordination of pain research across all NIH components, and ensure that results of NIH-supported pain research are widely disseminated.

In order to enhance research into RSD/CRPS, NINDS, together with other NIH Institutes, will convene a state of the science meeting on RSD/CRPS and other chronic pain conditions during FY2001. The meeting will bring together basic pain researchers, clinicians treating RSD/CRPS, NIH program staff, and patient advocacy representatives to review the current state of knowledge concerning the pathophysiology and treatment of RSD/CRPS and other chronic pain conditions, and identify promising future directions for research.

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Item: Stroke

Stroke remains the third leading cause of death, a leading cause of permanent disability, and a major contributor of late-life dementia. The Committee believes that an intensive research program on stroke should be a high priority for NINDS and NIH. The Committee urges the Institute to expand its stroke education program and to initiate and continue innovative approaches to improve stroke diagnosis, treatment, rehabilitation, and prevention through all available mechanisms, as appropriate, including the development of acute stroke treatment centers. In addition, as NINDS continues its strategic planning, the Committee encourages NINDS to work closely with the research community, clinicians, voluntary health organizations, and patient advocacy groups to discuss new avenues of basic and clinical stroke research opportunities. The Committee requests that the Director of the Institute be prepared to discuss plans for stroke research during the fiscal year 2002 appropriations hearing. In addition, the Committee encourages NINDS, in collaboration with the Centers for Disease Control and Prevention to examine the underlying causes of the regional disparity of stroke in the 'stroke belt' using all available technologies, as appropriate.

Action taken or to be taken
Stroke research is a high priority of NINDS because of the public health burden and the opportunities neuroscience presents for progress against stroke. The Institute's strategic plan, Neuroscience at the New Millennium, addresses research questions of importance to stroke in its discussion of neural environment and experimental therapeutics and clinical trials. Furthermore, in the reorganization of the structure of the NINDS extramural program, stroke research is supported by both the "Clinical Trials" and the "Neural Environment" program clusters.

The NINDS is committed to developing a five-year strategic research plan specifically for stroke. In initial meetings, the NINDS Director, leading experts in stroke research, and other NINDS senior staff have started identifying areas of opportunity as well as gaps in our knowledge about stroke. This process will involve the research community, clinicians, various organizations and stroke advocacy groups who will craft a research agenda for the next five years.

To bring important health messages to the public and in response to the mandate by Congress, NINDS has created a multi-faceted communication effort to raise awareness of the signs of stroke, the need for urgent action, and the possibility of a positive outcome with timely hospital treatment. NINDS is working closely with the Brain Attack Coalition (BAC), a group of professional, voluntary, and government groups dedicated to reducing the occurrence, disabilities, and death associated with stroke. The BAC has been significantly involved in NINDS' efforts to increase awareness of stroke symptoms and recently prepared a stroke symptom list that is now used by all participating BAC organizations. In the June 21, 2000, issue of the Journal of the American Medical Association (JAMA), NINDS and other members of the BAC presented the first clearly defined set of recommendations for hospitals to implement stroke centers, teams and other programs to improve stroke treatment in the United States. The announcement brought stroke into the national spotlight. NINDS also has created a checklist for communities entitled Do You Have Access To The Best Treatment For Stroke? On behalf of the Brain Attack Coalition, the NINDS has created a web-based resource for healthcare professionals to provide the latest tools for diagnosis and treatment of stroke.

As part of its campaign, Know Stroke. Know the Signs. Act in Time, NINDS developed a series of public education materials including: airport dioramas jointly sponsored with the National Stroke Association, billboard displays, consumer education brochures, exhibits, and new radio spots, all designed to increase awareness of stroke. NINDS also created and distributed "Ambulance," a television public service announcement (PSA) jointly sponsored by the Institute and several leading stroke organizations. The PSA has been viewed by millions of Americans. At the community level, NINDS partnered with the Black Commissioned Officers' Advisory Group of the U.S. Public Health Service and the American Stroke Association to host a stroke education and screening event. The event, called "Stroke Sunday," was held at Mt. Calvary Baptist Church in Rockville, Maryland and featured U.S. Surgeon General David Satcher as the keynote speaker discussing the need for more stroke awareness in the African-American community.

In the future, NINDS looks forward to the continued expansion of its stroke education efforts with a community education kit that will be distributed nationally to seniors communities, hospitals, pharmacies and through partnerships with African-American organizations.

The NINDS proposes to establish prevention/ intervention research networks throughout the extramural community, particularly in regions of the "Stroke Belt." The goal is to foster stronger linkages between investigators at minority and majority institutions with community-based organizations to improve minority recruitment and retention in clinical studies. As part of this program, NINDS, working with NHLBI and NCRR, is developing the "Stroke and Cardiovascular Prevention/Intervention Research Program." The pilot phase of this program is at the Morehouse School of Medicine in Atlanta, Georgia. NINDS is also developing the "Acute Brain Attack Research Program" in the Baltimore-Washington Area. This effort has already established a 24-hour stroke research care program at Suburban Hospital in Bethesda, Maryland, and our plan is to replicate this program in other medical facilities throughout the Baltimore-Washington metropolitan area, targeting those serving predominantly minority populations.

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Item: Sturge-Weber Syndrome

Sturge-Weber Syndrome is a congenital, non-familial disorder of unknown incidence and cause. The Committee commends the efforts of NIH to bring together the Office on Rare Diseases, NINDS, and other Institutes to examine this syndrome in a 1999 conference. The Committee encourages NINDS to pursue research on this syndrome through all available mechanisms, as appropriate, including a request for applications. The Committee requests that the Director be prepared to testify on the progress to improve the understanding of this syndrome at the fiscal year 2002 appropriations hearing.

Action taken or to be taken
NINDS, in conjunction with the National Institute of Child Health Human Development (NICHD) and the National Institute of Mental Health (NIMH), has issued a Program Announcement (PA) to invite exploratory research grant applications to facilitate the translation of fundamental neurobiology to the study of pediatric brain disorders. This PA identifies injury to the developing brain, a leading cause of death and disability in children, as an area of research need and opportunity. Its scope includes injuries due to vascular causes, and childhood cerebral vascular disease is generally secondary or related to vascular abnormalities such as those which occur in Sturge-Weber Syndrome (SWS), a disorder specifically cited in the program announcement. The SWS scientific conference co-sponsored by NINDS and the Office of Rare Diseases in June 1999, in conjunction with the Sturge-Weber Foundation, identified critical clinical care issues that might be addressed in clinical research investigations. Since then, the NINDS has been working with the Sturge-Weber Foundation and researchers to stimulate research applications - a process that can take from one to two years - and to explore future workshop ideas. The NINDS continues to maintain the excellent cooperation and interaction that has been established with researchers and patient advocates.

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FY 2001 Senate Appropriations Committee Report Language (S.Rpt. 106-293)

 

Item: Alzheimer's disease

NINDS recently co-sponsored two program announcements aimed at increasing the number of clinical trials for Alzheimer's disease. The Committee encourages NINDS to continue to assign this a high priority, and to continue its close working relationship with NIA, NIMH and NINR.

Action taken or to be taken
For many years, NINDS has supported research in many areas of Alzheimer's Disease, and the Institute is encouraged by recent developments in understanding the cellular and genetic basis of this disorder. In an effort to move preclinical findings to human testing as efficiently as possible, the Institute, along with the NIMH and NIA, issued two joint Program Announcements (PAs) encouraging the submission of Alzheimer's Disease Pilot Clinical Trial Planning Grants and Clinical Trial grant applications in early 1999. The ultimate effect of these program activities will not be known for some time, but the goal of these PAs is to enhance the development of clinical trials of pharmacological therapies for the cognitive and behavioral symptoms of Alzheimer's Disease. In addition, NINDS has undergone a recent reorganization which will enable the Institute to place a greater emphasis on Alzheimer's activities from a programmatic and planning perspective. At present, two of the Institute's seven new areas of research emphasis are Neurodegeneration and Clinical Trials. The development of a Neurodegeneration focus will enable staff to better coordinate Alzheimer's research activities with those of other degenerative diseases, such that research output is maximized in all areas. In addition, the focus on Clinical Trials has been designed to stimulate the numbers of clinical studies funded by the Institute, and to facilitate the planning and monitoring of these trials. It is anticipated that the area of neurodegenerative disease, including Alzheimer's, may derive significant benefit from this new effort. Lastly, NINDS will also coordinate its research activities in Alzheimer's Disease with all other ICs working in this field, including NIA and its Alzheimer's Disease Center Program, as well as NIMH and NINR.

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Item: Alzheimer's disease and PET Scans

The Committee urges NINDS, in collaboration with the National Institute on Aging and the National Institute of Mental Health, to expand its research into early diagnosis of Alzheimer's using PET imaging of the brain.

Action taken or to be taken
NINDS is acutely aware that the early diagnosis of Alzheimer's Disease, and other neurodegenerative diseases, is a critical first step in providing symptomatic relief to individuals affected, and to ultimately preventing or reversing disease pathology. Currently the Institute is funding several studies involving the development of improved imaging techniques in individuals with neurodegenerative disorders, including Alzheimer's. One of these projects is an extramural study evaluating the use of PET scanning to better define the relationship of cellular markers of degeneration to the clinical course of the disease. NINDS will also seek to establish collaborations with other ICs, such as NIA and NIMH, to facilitate research on PET scanning and other screening tools in Alzheimer's Disease.

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Item: Amyotrophic lateral sclerosis

The Committee applauds the Institute for its emphasis on research into the identification of neurodegeneration. The Committee encourages the Institute to consider a research planning workshop which would bring together ALS researchers and experts from other fields to foster new ideas and research directions that might lead to rapid advances in the understanding and treatment of ALS and related neurodegenerative diseases. The Committee also encourages the Institute to continue to expand and intensify its research efforts into ALS.

Action taken or to be taken
In March of 2000 NIH issued a request for applications soliciting proposals for research on amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, and other diseases that affect motor neurons. The response of the scientific community to that solicitation has been very encouraging, and review of the research proposals is underway. In April 2000 NINDS, working together with private organizations, held a workshop that brought together scientists from academia, industry and government to review current knowledge about what causes nerve cells to degenerate in these diseases, to discuss what we need to know to develop cures, and to consider the prospects for applying "high-throughput screening" technology to develop drugs to this end. High throughput screening uses robotics and miniaturized testing to rapidly screen large numbers of chemicals to find leads for drug development. Industry is less likely to apply this approach to relatively low prevalence disorders such as ALS. NINDS will continue its efforts to enhance research to find a cure for ALS, including programs in preparation that will help make high-throughput screening technology accessible to ALS researchers. NINDS also is intensifying its efforts in gene therapy, the biology of neurotrophic factors, and several other areas that hold promise for ALS and other neurodegenerative disorders.

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Item: Ataxia Telangiectasia

The Committee believes that more attention needs to be paid to pediatric neurodegenerative disorders. Insight into childhood diseases such as ataxia-telangiectasia (AT) will have applicability to all neurological disorders. Because the neurological manifestation of AT is the most pervasive and currently untreatable facet of this disease, the Committee encourages NINDS to allocate funds to neuroimaging research and other tools aimed at quantifying AT progression as well as assessing strategies for neuroprotection and therapies directed towards neural cell replacement.

Action taken or to be taken
Finding ways to treat pediatric neurodegenerative disorders is central to the NINDS mission, both because of the suffering these disorders cause and because progress in understanding normal and abnormal neural development may enhance efforts against other neurological diseases. For these reasons the Institute is placing increasing emphasis on research in childhood brain disorders. Recent actions include a solicitation encouraging exploratory research related to pediatric brain disorders, which is prompting strong interest in the scientific community, and a series of efforts, including a workshop and solicitations, focusing on the special problems of imaging of the young brain. The Institute is also intensifying its efforts in areas such as gene therapy of the nervous system and neural cell replacement research which may apply to many brain disorders that affect children and adults.

With regard to ataxia-telangiectasia, NINDS helped support the discovery of the gene defect that causes A-T and continues to support research about the normal functions of the ATM gene, how defects cause the disease, and ultimately on finding treatments. Recent studies have confirmed the initial expectation that A-T research has implications for many disorders, including cancer, but research has thus far not resulted in treatment. In April 1998, NINDS together with the A-T Children's Project held a meeting on the NIH campus focusing on the neurodegeneration in A-T and the Institute continues to encourage research specifically directed to the nervous system manifestations of this disease.

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Item: Batten disease

The Committee requests that NINDS be prepared to discuss the funding history and steps taken to increase research in this area. The Committee strongly urges that increased funding be provided to combat this devastating disease.

Action taken or to be taken
NINDS continues its long-term efforts to find cures for all forms of Batten disease. In April 1999 the Institute, working together with the Children's Brain Disease Foundation and the NIH Office of Rare Diseases, held a workshop to explore new directions for Batten disease research, and in June 1999 the Institute helped support an international conference on this disease. As part of its continuing efforts against Batten disease the Institute also hosted two additional workshops, one with a more global focus in November 1999 and another more focused on the genes CLN1 and CLN2 in May 2000. In July 2000 the Institute issued a program announcement to encourage scientists to apply progress in fundamental neuroscience to pediatric brain disorders. Through that program NINDS has funded new exploratory grants focusing on Batten disease. In addition to research targeted specifically to Batten disease, the Institute continues its broad efforts to overcome the common obstacles to gene therapy for all brain diseases, including a workshop on gene therapy for nervous system diseases held in October 2000.

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Item: Charcot-Marie-Tooth Disorder

The Committee urges the Institute to expand research in Charcot-Marie-Tooth Disorder. One of the most common inherited disorders, CMT affects approximately 150,000 individuals. Its victims slowly lose normal use of their hands and feet as nerves to the extremities degenerate.

Action taken or to be taken
Charcot-Marie-Tooth disorders (CMT) are the most common set of inherited peripheral nerve diseases in the United States. Several different forms of CMT occur, due to a variety of genetic defects. Specific mutations in several recently identified genes cause distinct types of CMT. Efforts are continuing to determine the genetic defects responsible for other types of CMT. Additional research is focused on learning how the identified gene defects cause CMT, with the hope of finding ways to halt or reverse the disease process. NINDS continues to encourage and support extramural and intramural research programs that address CMT.

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Item: Chromosome 18

NIH has supported little research into the abnormalities of chromosome 18, despite repeated urging by this Committee. The Committee again urges the Institute to ensure that the review process will adequately assess Chromosome 18 applications and to devote more research into this genetic abnormality.

Action taken or to be taken
Abnormalities of chromosome 18 impose very serious burdens on children and their families. Unfortunately, efforts to understand these syndromes confront formidable obstacles. Several different syndromes involve this chromosome, including problems reflecting missing pieces, duplications, and focused mutations of the genetic material. The symptoms resulting are many, diverse, and often affect the higher functions of the brain, which are the most difficult to understand. Recent progress in unraveling the human genome is providing tools and knowledge that will help in the study of these abnormalities. Several brain disorders, such as Niemann Pick C, bipolar disorder, Tourette syndrome, and dystonia, have been associated with genes on this chromosome, as have genes that have been recently found to be critical for brain development. This accumulating information provides clues to understanding chromosome 18 abnormalities. NINDS is increasing its efforts against all pediatric brain diseases including programs focused on imaging of the very young brain and on encouraging exploratory studies of these disorders.

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Item: Dystonia

The Committee continues to be pleased with NINDS's extramural research portfolio with respect to dystonia, and encourages NINDS to continue to expand the study of the DYT1 gene. In addition, the Committee encourages the Institute to expand its collaboration with the dystonia research community in supporting epidemiological studies on dystonia and in increasing public and professional awareness.

Action taken or to be taken
NINDS continues to support extramural and intramural research on the dystonias, including new and continuing grants. The broad program of research ranges from fundamental neuroscience studies that lay the groundwork for understanding what goes wrong with brain circuits in dystonia, through clinical studies in patients, to clinical trials of treatments. The Institute, working with private groups, is also sponsoring workshops on critical aspects of dystonia research, including a November 2000 international conference held on blepharospasm (a common form of dystonia that has not received much attention from researchers), a January 2001 meeting "From genes to function in dystonia," and a three day "Dystonia International Symposium" in September 2001. The NINDS Intramural program, which has long maintained an active research program on the dystonias, is enhancing its efforts to bring in and train fellows in dystonia research. The Institute has also updated its public information on dystonia and has redesigned its web site to make this and other information more accessible.

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Item: Epilepsy

The Committee encourages the Institute to target additional resources specifically to intractable epilepsy, which most often begins in childhood and is strongly associated with cognitive dysfunction due to the impact of uncontrolled seizures on the developing brain. The Committee is pleased that the Institute has sponsored the March 2000 conference `Curing Epilepsy: Focus on the Future' and expects an update on plans to advance promising areas of research identified during the conference at the fiscal year 2002 appropriations hearing.

Action taken or to be taken
NINDS is committed to both researching the causes and developing therapies for all forms of epilepsy. Although the Institute supports a wide range of projects in this field, all of the epilepsy research supported by NINDS has the potential to improve our understanding of intractable forms of the disease. In addition, the institute also funds many projects which are directly targeted to understanding and treating epilepsy in children, including intractable childhood epilepsy. As an example, NINDS is funding studies of the behavioral effects of epilepsy, and the development of fever-related seizures. NINDS-funded investigators are also exploring the mechanisms that cause the development of epilepsy in children, from rare genetic conditions that cause abnormal brain development, to factors that make the normal developing brain more susceptible to seizures. Improving imaging techniques and therapeutic strategies in treating children with epilepsy are also important goals of the Institute's epilepsy efforts.

On a broader level, NINDS planning in the area of epilepsy research was stimulated by the successful White House-initiated conference, entitled "Curing Epilepsy: Focus on the Future," held by NINDS in March 2000. This conference, a highly successful effort that brought together clinicians, basic scientists, and members of the epilepsy patient and advocacy community, was the starting point of a focused NINDS planning effort on epilepsy. This meeting was remarkably successful in bringing together a number of junior researchers, to stimulate their interest in epilepsy research. To build on this success, a new Request for Applications (RFA), entitled "Innovation in Translational Epilepsy Research for Junior Investigators," was announced at the meeting. The goal of this RFA is to stimulate junior researchers with expertise in fields such as clinical research, imaging techniques, and drug therapies, to bring their experience to bear in translating basic science research findings into treatments for epileptic conditions. Applications have been received and will be reviewed in March 2001. Another important outcome of the meeting was the development of a series of challenging but encouraging benchmarks by Institute staff and prominent epilepsy researchers. These benchmarks will be used to help investigators in the field of epilepsy research maximize their research efforts towards the translation of basic science research findings into improved clinical therapies that will prove a true "cure"- defined as "no seizures, no side effects" - for this disease. Several additional meetings are currently being planned in follow-up to the White House conference, including conferences on monotherapy, and the use of animal models in epilepsy research.

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Item: Holoprosencephaly

The Committee is pleased that NINDS is interested in funding new research for the treatment of holoprosencephaly, a severe neurological birth deficit affecting 1 in 5000 live births and 1 in 250 of all births. Recently, private organizations have made great strides towards understanding and treating this disorder, through establishing and funding three Clinical Centers of Excellence to treat holoprosencephaly. The Committee is encouraged by the recent First NIH Symposium on Holoprosencephaly, and encourages the NINDS and other relevant institutes to significantly increase their multi-disciplinary activities aimed at understanding and treating this disease.

Action taken or to be taken
Holoprosencephaly (HPE) is the most common developmental defect of the brain and face in which the cerebral hemispheres of the brain fail to separate into distinct left and right hemispheres due to the improper formation of the forebrain during early embryonic development. It results in varying degrees of facial abnormalities and mental retardation. At least 12 different loci have been associated with HPE, and most recently, an international team led by scientists at the National Human Genome Research Institute (NHGRI) located the fourth identified gene associated with HPE, dubbed TGIF, on chromosome 18. There may be at least eight more genes on different chromosomes.

The astonishing growth in molecular genetics has provided the field of developmental neurology with new perspectives and tools for unraveling its mysteries and for studying developmental anomalies of the nervous system such as HPE. With the success of the Human Genome Project, there is further promise that the identification of genes involved in HPE will advance more rapidly. In the past year, the NINDS competitively funded several new investigator-initiated research projects investigating gene expression and function in HPE. In addition, holoprosencephaly is one of the disorders of anomalous development specifically identified in an ongoing Program Announcement issued by the NINDS, in conjunction with the National Institute of Child Health Human Development (NICHD) and the National Institute of Mental Health (NIMH), to invite exploratory research grant applications to facilitate the translation of fundamental neurobiology to the study of pediatric brain disorders.

The "1st NIH Conference on Holoprosencephaly," sponsored by NHGRI and the NIH Office of Rare Diseases, consisted of two separate, consecutive programs: one focused on scientific research related to HPE, and the other a family-oriented program exploring the problems that families with an HPE member encounter. Activities also provided for an exchange of information between parents and various specialists including neurologists, geneticists, genetic counselors, and physical therapists. The proceedings are being documented in a paper appropriate for journal publication. NHGRI also has an active protocol recruiting parents whose child was diagnosed before birth with HPE to develop information for more effective strategies for helping parents who face similar prenatal diagnoses.

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Item: Lyme disease

The Committee urges the Institute to study central nervous system abnormalities associated with Lyme disease. The committee therefore urges that diagnostic techniques including brain imaging and improved treatment protocols be designated as research priorities. The Committee is encouraged by a recent grant for brain imaging in neuroborreliosis patients. The Committee also urges the Institute to study peripheral nervous system abnormalities associated with Lyme disease.

Action taken or to be taken
The clinical trial cited above was recently funded by NINDS to evaluate PET and MRI imaging of Lyme disease patients who have long-term neurological abnormalities. The study will determine the efficacy of the antibiotic ceftriaxone in these patients, examine brain imaging abnormalities associated with persistent Lyme encephalopathy and identify markers or methods to monitor antibiotic responsiveness.

Another NINDS research project is focused on answering such questions as how frequently the spirochete B. burgdorferi, the agent that causes Lyme disease, invades the nervous system, how long the infection persists in the central nervous system, which cells of the nervous system are infected by the parasite, and how the immune system suppresses the invasion.

A large NINDS program project, "Neurologic Aspects of Lyme Disease in North America," will comprehensively explore the genetic makeup of B. burgdorferi, and study the course of Lyme disease in adult and pediatric patients.

The NINDS and NIAID are jointly supporting a contract "Non-Human Primate Animal Models for Research on Chronic Lyme Disease," which will provide a unique opportunity to elucidate the role of cells that generate antibody responses to B. burgdorferi.

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Item: Neurodegenerative disorders

The Committee is encouraged by the level of emphasis placed on neurodegenerative disorders research within NINDS and across NIH. The Committee continues to support research investigating the role of neurotransmitters in neurodegenerative disorders.

Action taken or to be taken
Attacking neurodegenerative diseases continues to be a major goal of the NINDS. The public health costs associated with disability and death due to neurodegenerative diseases are staggering. The NINDS Strategic Plan and its Implementation emphasize our goal to lessen the burden of neurodegenerative disorders over the entire human life span. Our investment in neuroscience research and the resulting progress in understanding have set the stage for a new generation of diagnostics and treatments. Many researchers believe that we are nearing a quantum leap in our ability to treat neurodegenerative disorders. Fundamental breakthroughs in our understanding of how the brain works are fueling efforts to develop novel prevention and treatment strategies. Exciting research in areas such as the genetic basis of disease, natural nerve cell growth and survival factors, and brain plasticity is being applied to clinical problems through translational research sponsored by the NINDS. NINDS is committed to capitalizing on our recent progress in neuroscience to combat neurodegenerative disease, and will continue to vigorously support research programs that combat neurodegeneration at every stage of life.

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Item: Neurofibromatosis

The Committee is aware that recent advances in NF research have linked NF to cancer, brain tumors, learning disabilities and heart disease. Because of the enormous promise of NF research, the Committee encourages NINDS to expand its NF basic and clinical research portfolio including clinical trials. The Committee is pleased that the Institute has initiated a trans-institute workshop on NF to be held this spring and encourages the Institute to continue to coordinate its efforts with other Institutes engaged in NF research. The Committee also requests that the Institute be prepared to report on the status of the NF research portfolio at its fiscal year 2002 appropriations hearing.

Action taken or to be taken
The NINDS continues to support a range of research directed at and related to the neurofibromatoses - from the genetics of NF1 and NF2 to the neurological dysfunctions, cognitive and behavioral, associated with NF1. The Institute also coordinates its efforts with several other NIH institutes with an interest in NF: the National Cancer Institute (NCI) has a significant investment in research on tumor suppressor genes and the tumors and malignancies associated with NF; the National Institute on Deafness and Other Communication Disorders (NIDCD) on taste and hearing impairments associated with acoustic neuromas; the National Eye Institute (NEI) on the role of the NF2 gene in cataract formation; the National Institute of Child Health and Human Development (NICHD) on learning disabilities; and the National Heart, Lung, and Blood Institute (NHLBI) on the NF1 gene and cardiac development.

In May 2000, NINDS hosted a two-day workshop to assess the status of NF research and to identify future research opportunities to be developed in FY2001. In addition to a panel of 17 extramural basic scientists and clinicians, the meeting included representatives from the other five NIH institutes (NCI, NICHD, NEI, NHLBI, and NIDCD), two other federal agencies with NF research programs (the Department of Defense and the Veterans Administration), the pharmaceutical industry, and two national NF patient advocacy groups. Several priorities were agreed upon, including development of more refined animal models for NF1 and NF2; further analysis of the mechanisms of action of neurofibromin and merlin - the proteins whose functions are disrupted in NF1 and NF2, respectively; and the identification of modifier genes that affect the expression of neurofibromin and merlin. The results of this workshop were subsequently discussed with the broader NF research community at the annual meeting of the International Consortium for the Molecular and Cell Biology of NF1 and NF2. The NINDS is working on developing several new NF- related activities to respond to the research needs and priorities identified through these meetings, and to stimulate interest in NF research from non-NF researchers.

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Item: Outreach

The Committee commends NINDS for its public education and outreach programs. The Committee encourages NINDS to continue these efforts, with special attention to innovative approaches to outreach, education, and recruitment and retention of staff.

Action taken or to be taken
NINDS has significantly expanded its education and outreach programs in the past year. A major redesign of the Institute's website is linked to information on clinical trials and journal references provided through the National Library of Medicine. The public liaison function has been enhanced through the recruitment of an experienced staff member. The Institute's fiftieth anniversary provides additional opportunities for education and outreach, and will feature the publication of a history of neuroscience research at NIH.

Outreach efforts to specific populations at risk for neurological diseases, especially stroke, continue to grow. For example, NINDS staff recently joined U.S. Surgeon General David Satcher at a local church for Stroke Sunday, a health education and stroke event co-sponsored by the American Stroke Association (ASA) and the Black Commissioned Officers' Advisory Group of the U.S. Public Health Service (BCOAG). The event brought attention to the major impact of stroke in the African American community and helped to inform church congregants about reducing their stroke risks.

The institute recently produced a CD and developed a website to help promote the Institute's efforts to increase the representation of underrepresented minorities, women, and individuals with disabilities for the various NINDS neuroscience research training programs. Expanded and innovative recruitment efforts continue to bear fruit in the form of outstanding scientific and managerial staff who have joined the NINDS staff.

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Item: Paralyzed vocal cords

The Committee expects the Institute to collaborate with NIDCD on the development or adaptation of electrical stimulation devices. These devices would activate the reflexes of the paralyzed muscles that open the airway during breathing in cases of paralyzed vocal cords due to trauma or neurodegenerative disease.

Action taken or to be taken
NINDS is currently supporting two research studies that involve the development of technology which may help reverse the effects of vocal cord paralysis. Both of these projects are focused on the development of improved electrodes that can be used reliably to stimulate nerves in a chronic implantation setting. One of these researchers is collaborating with investigators supported by NIDCD, who are evaluating the efficacy of electrical stimulation techniques in an animal model of laryngeal paralysis. In addition, a number of other NINDS-funded projects in the fields of electrode development and neural stimulation, though not immediately targeted to restoring function to paralyzed vocal cords, may ultimately benefit individuals with this condition.

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Item: Parkinson's Disease

The NIH Director should be prepared to discuss Parkinson's disease research planning and implementation for fiscal year 2001 and 2002 during the hearings on the fiscal year 2002 budget.

Action taken or to be taken
NINDS is committed to a broad-based approach to understanding and treating Parkinson's Disease through the continued development of both intramural and extramural research activities.

In January 2000, NIH held a Parkinson's Disease planning conference in response to a Congressional request to develop a long-term research agenda in this area. This conference included NIH staff, researchers, clinicians, and advocacy group representatives. Based on the recommendations from this meeting, NINDS, along with several other institutes, developed a five-year plan for research on Parkinson's, which was released in March 2000. This plan outlines a number of aggressive strategies that the NIH will utilize in enhancing research progress in this area. Specific targets for further exploration that are identified in this plan include the risk factors and underlying causes of the disease, the genetic and cellular causes of cell death, changes to neuronal circuitry, pharmacological and surgical approaches to treatment, gene therapy treatment approaches, advances in genetic technology, new animal models, improvements in imaging techniques, high throughput drug screening, and the establishment of repositories for affected brain tissue.

NINDS has developed a Parkinson's Disease Implementation Committee that includes Institute staff, extramural researchers, and members of the advocacy community. This Committee, which has held two meetings since March, will monitor the progress that the Institute makes on its Parkinson's planning effort, and suggest new directions for implementation. NINDS has taken several actions to make progress on the plan as rapidly as possible. In March 2000, a meeting of representatives of the 11 currently funded Morris K. Udall Parkinson's Disease Research Centers of Excellence was held, with the overall goal being to discuss research being conducted at each center and to coordinate ongoing and future collaborations. NINDS has awarded supplements to Udall centers for critical projects such as expediting drug discovery, identifying Parkinson's genes, and investigating Parkinson's disease in minority populations. Other program actions have also been taken, including publication of a Request for Applications (RFA) on Parkin, a protein implicated in the early-onset forms of Parkinson's. Several projects were funded from an RFA on Deep Brain Stimulation, a novel therapy that holds promise for providing effective symptomatic treatment for some Parkinson's patients, and a follow-up RFA will focus on other aspects of this form of therapy. In addition, Parkinson's Disease was a highlight of two recent meetings sponsored by the Institute, the first a workshop on Gene Therapy, and the second a meeting of the Therapeutic Opportunities in Parkinson's Disease Working Group, both held in October 2000. The latter workshop was designed to help focus a solicitation on Parkinson's therapies that the Institute plans to issue.

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Item: Reflex Sympathetic Dystrophy (RSD)

The Committee urges NINDS to increase funding for further research into RSD in the hope that early detection can lead to completely effective treatment.

Action taken or to be taken
The NINDS supports a large and varied portfolio of pain research, including research on chronic pain conditions such as Reflex Sympathetic Dystrophy (RSD, also known as Complex Regional Pain Syndrome (CRPS)). This includes studies aimed at both understanding the basic mechanisms of pain and at developing more effective treatments for relieving pain. Together with National Institute of Dental and Craniofacial Research, NINDS leads the NIH Pain Consortium, which was established in 1997 to encourage information sharing and collaborative research efforts, provide coordination of pain research across all NIH components, and ensure that results of NIH-supported pain research are widely disseminated.

In order to enhance research into RSD/CRPS, NINDS, together with other NIH Institutes, will convene a state of the science meeting on RSD/CRPS and other chronic pain conditions during FY2001. The meeting will bring together basic pain researchers, clinicians treating RSD/CRPS, NIH program staff, and patient advocacy representatives to review the current state of knowledge concerning the pathophysiology and treatment of RSD/CRPS and other chronic pain conditions, and identify promising future directions for research.

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Item: Spinal Cord injury

The Committee is pleased to learn of the exciting scientific advances being made on several fronts which hold much promise for progress against the devastating and lifelong effects of spinal cord injury. Research to promote regeneration and restore function to the injured spinal cord is proceeding along two promising and complementary lines- implantation of cells and modification of the injury site's environment to promote functional recovery. A particularly exciting approach involves the implantation of pluripotent, neural stem cells- undifferentiated progenitor cells with the potential to replace damaged components of the central nervous system. In addition to traditional funding mechanisms, the Committee understands that this area of research may benefit from efforts to promote new types of collaborations and to build on currently funded projects that could be expanded to include stem cell research. The Committee urges the NINDS to aggressively pursue and initiate studies that will hasten progress to restore function to the injured spinal cord and offer hope to victims of spinal cord injury and their families. The Committee expects NINDS to report on its progress in promoting research on cell replacement in spinal cord injury at its fiscal year 2001 appropriations hearing.

Action taken or to be taken
For many years, NINDS has made the development of therapies to treat spinal cord injuries an Institute priority. In 1999, NINDS held a workshop to review the status of stem cell research and to identify gaps in our understanding of this field, and the recent reorganization of the Institute has enabled staff to increase their focus on Neural Repair and Plasticity as a special area of emphasis. Within the field of spinal cord injury research, NINDS is supporting and closely monitoring the field of cell replacement therapy and other promising approaches. Currently, the Institute funds a wide range of research studies on cell replacement therapy for spinal cord injury and other neurological disorders, including research on pluripotent stem cells in animals designed to evaluate the ability of these cells to replace damaged or destroyed nerve tissue.

NINDS is also stimulating progress towards improved treatment for spinal cord injury by convening a series of small, highly-focused workshops, entitled: "New Strategies in Spinal Cord Injury." Two workshops in this series have already been held, and several more are planned through 2001. Each workshop focuses on a particular problem in the field of spinal cord injury research, drawing both spinal cord researchers and investigators from outside the field who can contribute a new perspective to these tightly focused topics. The goal of these meetings is to review recent research advances, and to develop novel strategies for treating spinal cord injury, emphasizing a multidisciplinary, collaborative approach.

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Item: Stroke

The committee understands that the next phase of NINDS strategic planning will include an in-depth review of progress and opportunities for specific disorders or groups of disorders. The Committee urges NINDS to work closely with the research community, clinicians, voluntary health organizations and patient advocacy groups to apply this approach to stroke. The review should identify promising new avenues of basic and clinical stroke research and address resources, including infrastructure and funding mechanisms, needed for progress against stroke. The Director should be prepared to discuss plans and implementation steps for stroke research at next year's hearings.

Action taken or to be taken
Stroke research is a high priority of NINDS because of the public health burden and the opportunities neuroscience presents for progress against stroke. The Institute's strategic plan, Neuroscience at the New Millennium, addresses research questions of importance to stroke in its discussion of neural environment and experimental therapeutics and clinical trials. Furthermore, in the reorganization of the structure of the NINDS extramural program, stroke research is supported by both the "Clinical Trials" and the "Neural Environment" program clusters.

The NINDS is committed to developing a five-year strategic research plan for stroke. In initial meetings, the NINDS Director, leading experts in stroke research, and other NINDS senior staff have started identifying areas of opportunity as well as gaps in our knowledge about stroke. This process will involve the research community, clinicians, various organizations and stroke advocacy groups who will craft a research agenda for the next five years.

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Item: Stroke and PET scans

The Committee encourages NINDS to expand its research efforts into the utility of PET scans of the brains of stroke victims to determine whether brain tissue damage from stroke may be reversible.

Action taken or to be taken
Neuroimaging provides an unprecedented opportunity to study the living human brain, and permits observation of the parts of the brain that are active when we move, think, feel, and learn. Technologies like positron emission tomography (PET), spectroscopy (MRS), and functional magnetic resonance imaging (fMRI) hold great promise for non-invasive assessment of brain activity and damage during and following a stroke. The findings offered by these new methods have the potential for a dramatic impact on the assessment of pathophysiological status at the time of diagnosis and during the course of acute treatment, as well as on the prognosis of long-term functional outcome. Establishing PET technology at medical centers to examine stroke patients requires a round-the-clock coordinated effort of a team with expertise in several fields to create the short-lived diagnostic isotope on site, to operate the imaging equipment and analyze the scans. However, we believe that PET imaging should be pursued, as it holds promise for evaluating stroke severity and shaping treatment strategies.

The NINDS is currently supporting research that is using PET imaging to examine language impairment and changes in local cerebral blood flow after stroke.

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Item: Stroke in women

The Committee urges the Institute to increase research specifically in the area of stroke-related care, risk factors, preventive strategies, acute stroke management and aspects of post-stroke recovery among women. The Committee further urges the Institute to take steps to increase research into new therapies for stroke in women as well as ways of enhancing the vascular health of all Americans.

Action taken or to be taken
The NINDS supports a controlled clinical trial in post-menopausal women who have had a recent transient ischemic attack (TIA) or non-disabling stroke. The study follows subjects for up to five years to determine if estrogen therapy reduces the risk of death or recurrence of stroke. The goal is to verify the findings of previous epidemiological studies. This women's estrogen for stroke trial or "WEST" study is significant for the promise it holds for stroke treatment in general and for the potential health benefit to postmenopausal women in particular. Additionally, other NINDS-supported investigators are studying why women with low bone density are more prone to stroke. To further elucidate gender differences in stroke risk, an NINDS grantee is using animal models to look at basic, biological vascular and neural sex-linked features, including the role of estrogen and estrogen receptors.

Novel post-stroke therapies are being evaluated on patients of both sexes. Women are well represented in all other NINDS stroke clinical studies, and will likewise benefit from salient findings.

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Item: Stroke in women

The committee also encourages the creation of acute stroke research or treatment research treatment centers to provide rapid, early, continuous 24 hour treatment to stroke victims including the use of the clot buster drug tPA, if appropriate. A dedicated area in a medical facility with resources, personnel team and equipment to treat stroke, would also provide an opportunity for early evaluation of stroke treatments.

Action taken or to be taken
Stroke presents an excellent example of how research findings can be effectively used to create educational efforts aimed at the acute care community and the public. For example, NINDS is working closely with the Brain Attack Coalition (BAC), a group of professional, voluntary, and government groups dedicated to reducing the occurrence, disabilities, and death associated with stroke. The BAC has been significantly involved in NINDS' efforts to increase awareness of stroke symptoms and recently prepared a stroke symptom list that is now used by all participating BAC organizations. In the June 21, 2000, issue of the Journal of the American Medical Association (JAMA), NINDS and other members of the BAC presented the first clearly defined set of recommendations for hospitals to implement stroke centers, teams and other programs to improve stroke treatment in the United States. The announcement brought stroke into the national spotlight. NINDS also has created a checklist for communities entitled Do You Have Access To The Best Treatment For Stroke? On behalf of the Brain Attack Coalition, the NINDS has created a web-based resource for healthcare professionals to provide the latest tools for diagnosis and treatment of stroke.

In January, 2000 the NINDS announced the implementation of a 24 hour stroke team at Suburban Hospital im Bethesda. The team, a combination of Suburban and NINDS neurologists, internists, intensive care physicians, nurses, radiologists, researchers and rehabilitative therapists will be available to stroke patients who come in at any time of the day or night. Located right across the street from NIH, Suburban Hospital partnered with NIH for the first time last summer when they launched a study to evaluate whether advanced magnetic resonance imaging (MRI) would improve the emergency diagnosis of stroke and heart attack. The research protocols will be conducted by both the NINDS and the National Heart, Lung and Blood Institute. It is encouraging to note that since this program was instituted at Suburban Hospital, the use of tPA treatment for stroke has increased there three-fold. The NINDS hopes to replicate this program at other medical centers in the Baltimore-Washington Area that serve at-risk populations. Additionally, this program will be a model for creating acute stroke centers or "Acute Brain Attack Research Programs" across the country.

Recently, a national stroke coalition announced that it advocated that all hospitals establish stroke centers or other programs to reduce deaths and disabilities from stroke. The chair of the Brain Attack Coalition is the former director of stroke, trauma and neurodegenerative disorders at the NINDS.

The NINDS, working with NHLBI and NCRR, is developing the "Stroke and Cardiovascular Prevention-Intervention Research Program." The pilot phase of this program is at the historically minority institution, the Morehouse School of Medicine in Atlanta, Georgia.

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Item: Traumatic Brain Injury

The Committee is aware of the development of scientific, evidence-based guidelines for TBI and encourages the Institute to educate trauma centers staff and others about these guidelines.

Action taken or to be taken
More than 2 million head injuries occur each year. Of these, approximately 100,000 victims die and 500,000 require hospitalization. Those who survive traumatic brain injury (TBI), often have serious cognitive, emotional and behavioral problems, as well as the need for long-term rehabilitation. Surveillance data from the Centers for Disease Control and Prevention estimates that there are more than 5.3 million Americans living with a disability as a result of a brain injury, and the social and economic costs are staggering. Improving the survival and outcomes of all brain injury patients is an essential goal of the NINDS, as reflected in the research agenda. Major emphasis is placed on the prevention of secondary damage, preservation of neurons and neural circuits, and regeneration and plasticity. NINDS grantees are exploring a variety of interventions to limit damage resulting from trauma and to promote repair of the damaged nervous system, as well as conducting research on ways to promote recovery of cognitive and language function following brain injury.

The Guidelines for the "Management and Prognosis of Severe Traumatic Brain Injury" were published in the June/July 2000 issue of the Journal of Neurotrauma. These guidelines were a joint venture of The American Association of Neurological Surgeons and The Brain Trauma Foundation, which holds the copyright; neither NINDS nor any other NIH institute was involved in the development or review of these Guidelines. Broad dissemination of these evidence-based guidelines, which attempt to bridge the gap that sometimes exists between scientific research and clinical application, could advance the care and outcomes of traumatically brain-injured patients. However, only federal or state government sponsored guidelines can be searched from the National Library of Medicine's (NLM) Health Services/Technology Assessment Text (HSTAT) collection, and the journal in which they were first published does not provide a full-text link from PubMed which is operated by the NLM. As a result of discussions with the NLM and the Agency for Healthcare Research and Quality (AHRQ), it appears that the Guidelines could be made widely available to health care professionals through the National Guideline Clearinghouse (NGC). The NGC is maintained by AHRQ in partnership with the American Medical Association and the American Association of Health Plans, who set minimum inclusion criteria for guidelines published on its site. This information was provided to The Brain Trauma Foundation. In addition, NINDS is exploring whether other avenues for review and distribution of the Guidelines might be available through programs of the Health Resources and Services Administration (HRSA).

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Last Modified July 10, 2012