NIH Blueprint empowers drug development for nervous system disorders

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For release: Thursday, August 18, 2011

First awards will fund seven teams across the country

The National Institutes of Health has made awards to investigators across the United States for an ambitious set of projects seeking to develop new drugs for disorders of the nervous system.

The projects – aimed at treating conditions such as vision loss, neurodegenerative disease and depression – are funded through the NIH Blueprint for Neuroscience Research.  The NIH Blueprint pulls together 15 of the agency's institutes and centers, leveraging their resources to confront major, cross-cutting challenges in neuroscience research. The Blueprint Neurotherapeutics Network will serve as a resource enabling investigators to develop new drugs for nervous system disorders and prepare them for clinical trials, and will be funded at up to $50 million over five years.

For decades, public funding from NIH has helped academic labs and small businesses use their ingenuity to pursue new strategies for treating nervous system disorders.  However, many labs often lack the resources – time, money, scientific staff, and regulatory expertise – to turn a promising strategy into an effective treatment.  The new initiative places these investigators at the helm of an expert drug development team that includes pharmaceutical industry consultants and service contractors.

"The Blueprint Neurotherapeutics Network will pair neuroscientists with experts in therapy development, and enable them to pursue their most exciting ideas for new drugs without having to redirect the focus of their laboratories," said Story Landis, Ph.D., director of NIH's National Institute of Neurological Disorders and Stroke (NINDS), which is a member of the NIH Blueprint.

Nervous system disorders affect tens of millions of Americans, and there is a substantial unmet need for treatment.  But the process for developing new drug therapies is costly and carries high risk.  Only about 10-20 percent of candidate drugs for all disease indications survive the early phases of development and reach clinical trials.  And development of treatments for disorders affecting the nervous system may face special hurdles.  For example, many such disorders are individually rare, which means they present small markets for drug companies.

Before a new compound can move into clinical trials, its chemical structure must typically be redesigned to transform it into a safe and effective drug, a process called chemical optimization.  Hundreds of chemical variations must be tested and retested in cell-based systems and animal models to find one with the desired effects.

Project teams supported by the Blueprint Neurotherapeutics Network receive research funding, plus access to millions of dollars worth of services normally only available to pharmaceutical companies.  The pharmaceutical and biotechnology industry consultants will assist investigators throughout the drug development process, from chemical optimization, to biological testing, to advancing the drug into early-stage clinical trials.  Each project team will be required to meet a set of interim goals, or milestones, to continue to receive funds and access to Blueprint resources.

The Blueprint has made awards to seven research teams at six academic institutions and one drug discovery company.  Detailed information about the seven projects is available at http://www.neuroscienceblueprint.nih.gov/bpdrugs/bpn.htm.  The project teams and their strategies are:

• Brigham and Women's Hospital, Cambridge, Mass., and Ohio State University, Columbus
  Principal Investigators:  Marcie Glicksman, Ph.D., Gregory Cuny, Ph.D. and Chien Liang Lin, Ph.D.
  Disorder:   Amyotrophic lateral sclerosis (ALS)
  Strategy:  To slow the onset of paralysis in ALS by reducing toxic levels of the brain chemical glutamate.  The compounds under study work by stimulating EAAT2, a protein that enables cells to essentially vacuum up excess glutamate.
• Columbia University, New York City
  Principal Investigator:  Konstantin Petrukhin, Ph.D.
  Disorder:  Age-related macular degeneration (AMD)
  Strategy:  To slow the course of dry AMD, which occurs when cells in the eye degenerate, due in part to the chemistry of vision.  A derivative of retinol (a form of Vitamin A) is needed for vision, but it also generates a toxic byproduct.  The compounds under study would reduce retinol levels in the eye.
• Emory University, Atlanta
  Principal Investigator:  Raymond Dingledine, Ph.D.
  Disorder:  Stroke
  Strategy: To pharmacologically enhance the activity of EP2, a receptor for prostaglandins. Prostaglandins are primarily known for their role in inflammation, but activation of the EP2 receptor has protective effects in animal models of stroke.
• Trevena, Inc., King of Prussia, Pa.
  Principal Investigator:  Michael William Lark, Ph.D.
  Disorder:  Depression
  Strategy:  To develop faster antidepressants that tap into the body's system of natural feel-good chemicals known as endorphins.  The compounds under study activate the delta-opioid receptor, which is involved in the brain's response to endorphins.
• University of California, San Diego
  Principal Investigator:  Steven Wagner, Ph.D.
  Disorder:  Alzheimer’s disease
  Strategy:  To develop selective modulators of an enzyme responsible for producing Abeta-42, a protein fragment that accumulates in the brains of people with Alzheimer’s disease.  Abeta-42 is believed to play a critical role in brain cell death and dementia.
• University of Miami, and Miami Project to Cure Paralysis
  Principal Investigators:  John Bixby, Ph.D., Vance Lemmon, Ph.D. and Jeffrey Goldberg, M.D., Ph.D.
  Disorder:  Optic neuropathy (damage to the optic nerves)
  Strategy:  To develop compounds that help injured fibers in the optic nerve regenerate and grow through scar tissue.  Damage to the optic nerves, which connect the eyes to the brain, is a common cause of vision loss.
• University of Washington, and Fred Hutchinson Cancer Research Center, Seattle
  Principal Investigators:  Edwin Rubel, Ph.D., David Raible, Ph.D. and Julian Simon, Ph.D.
  Disorders:  Hearing loss and balance disorders
  Strategy:  To develop compounds that prevent the damaging effects certain antibiotics and anticancer drugs can have on cells inside the ear.  The team is testing compounds in larval zebrafish, which use similar cells to detect vibrations in water.

"The investigators get access to the same resources and expertise that drug companies have," said Jill Heemskerk, Ph.D., a program director in the NINDS Office of Translational Research and the lead contact for the Blueprint Neurotherapeutics Network.  "The investigators will retain intellectual property rights for any drugs they develop through the network.  Our hope is that pharmaceutical companies will license the most promising drugs and invest in the clinical studies needed to bring them to market." 

The Blueprint Neurotherapeutics Network has issued another request for applications with a deadline of Dec. 15, 2011.  Given that only 10-20 percent of the compounds under investigation are likely to survive preclinical development, the network will fund as many as 20 projects, with the goal of bringing at least two to four compounds into early clinical trials.  Applicants must have at least one lead compound, as well as the biological assays for evaluating derivative compounds made during the optimization process.

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The NIH Blueprint for Neuroscience Research (www.neuroscienceblueprint.nih.gov) is a cooperative effort among the NIH Office of the Director and the 15 NIH Institutes and Centers that support research on the nervous system. By pooling resources and expertise, the Blueprint supports transformative neuroscience research, and the development of new tools, training opportunities, and other resources to assist neuroscientists.  The Blueprint Neurotherapeutics Network is one of the Blueprint Grand Challenges, which are intended to promote major leaps in the understanding of brain function and in approaches for treating brain disorders.  For more information, visit http://neuroscienceblueprint.nih.gov/research_funding.htm.

NINDS (www.ninds.nih.gov) is the nation's leading funder of research on the brain and nervous system. The NINDS mission is to reduce the burden of neurological disease – a burden borne by every age group, by every segment of society, by people all over the world. 

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

Reporters:  For more information, call 301-496-5924 or go to www.ninds.nih.gov/PressRequest/.

Last Modified October 28, 2011