Amyotrophic Lateral Sclerosis, or ALS, is a progressive and fatal neurodegenerative disease, affecting around 30,000 people in the United States. Although some cases of ALS are inherited, the majority are sporadic, meaning that they occur with no known family history. In people with ALS, motor neurons, the nerve cells in the brain and spinal cord that control voluntary muscle movement and breathing, degenerate and die, which causes muscles to weaken and waste away. There is no treatment to reverse damage to motor neurons or cure ALS at this time. The goals of NINDS’s ALS research are to understand the cellular mechanisms involved in the development and progression of the disease, investigate the influence of genetics and other potential risk factors, identify biomarkers, and develop new treatments. No matter what the cause, ALS is devastating for people with the disease and their family members and caregivers. People living with ALS, their loved ones, and their caregivers are fighting against an unfair ALS clock, which is often tragically short. Sadly, many people with ALS die within three to five years of symptom onset, so there is great urgency to find better treatments for the disease. I would like to share some updates on how NINDS has been implementing the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS).
The bill, which President Biden signed into law on December 23, 2021, called for a research grant program at NIH that uses data from the Food and Drug Administration (FDA)’s expanded access to experimental drugs pathway for individuals who are not eligible for ALS clinical trials. Under the ACT for ALS, NIH recently funded a new expanded access research grant. In this project, a research team led by Bjorn Oskarsson, M.D. at the Mayo Clinic in Florida, and working with WideTrial and MediciNova, will examine the effects of a six-month treatment course of ibudilast in 200 people with ALS. Ibudilast is an anti-inflammatory drug that may have neuroprotective effects by blocking phosphodiesterases, enzymes that break down messenger molecules called cyclic nucleotides inside cells, thereby affecting a host of cellular responses, including inflammation.
The ACT for ALS also called for the establishment of a public private partnership (PPP) for ALS. The ACT for ALS PPP includes three closely integrated components: the Critical Path for Rare Neurodegenerative Diseases (CP-RND), which was announced in 2022; the Access for All in ALS (ALL ALS) Clinical Research Consortium; and the Accelerating Medicines Partnership® for Amyotrophic Lateral Sclerosis (AMP® ALS).
AMP® ALS officially launched in May 2024. This is a collaborative effort managed by the Foundation for the NIH and includes NIH, FDA, and over a dozen private sector partners. The primary goal of AMP® ALS is to accelerate the development of effective treatments and biomarkers for all forms of ALS. In order to achieve this, AMP® ALS is creating a knowledge portal for genetic, molecular, and clinical data, and analyzing biofluids (blood, cerebral spinal fluid) and post-mortem tissue collected by the ALL ALS consortium and other natural history studies. AMP® ALS is bringing together data and biospecimens from many different studies, including ACT for ALS expanded access studies like Dr. Oskarsson’s mentioned above, the ALL ALS consortium, and more. Providing access to centralized, comprehensive datasets and associated biospecimens will promote advancements in therapy development and the identification of improved biomarkers, clinical outcome measures, and other research tools that will enable more efficient clinical trials and better diagnosis and treatment.
The ALL ALS Clinical Research Consortium, which was first announced in 2023, is operationalizing the research objectives of AMP® ALS. The consortium will enroll over 2000 people living with ALS or at genetic risk for developing the disease as part of a large-scale natural history study. This study will also include standardized collection of biospecimens, which will be made available to the research community through established NIH biorepositories, as well as data harmonization and sharing through the ALS knowledge portal. Together, these efforts will be integral to support AMP® ALS in achieving its goals of accelerating therapy development and improving disease diagnosis. The ALL ALS Clinical Research Consortium includes 35 clinical sites across the U.S. and Puerto Rico and is led by two coordinating centers located at Massachusetts General Hospital (Boston, MA) and St. Joseph’s Hospital and Medical Center (Phoenix, AZ). The ALL ALS Consortium recently announced enrollment of the first participant, an important milestone in this study. To learn more about this study or to enroll, please contact: ALLALS_Info@dignityhealth.org.
It is important to note that ACT for ALS programs are supplementary to the continual support for NIH- and NINDS-funded investigator-initiated ALS research, which has set the stage for some exciting recent advancements. For instance, last year, the U.S. Food and Drug Administration (FDA) approved tofersen for the treatment of people with ALS who have been determined to have a mutation in the SOD1 gene. This work was based in part on NINDS-funded research. Earlier this year, we announced that researchers at NIH, including those within our NINDS Division of Intramural Research, detected abnormal proteins in the spinal fluid of people with ALS and frontotemporal dementia (FTD), which could help accelerate diagnosis of these diseases. More recently, NIH-funded researchers published a study describing how their newly-developed brain-computer interface (BCI) translated brain signals into speech with up to 97% accuracy in a person with severely impaired speech due to muscle weakness caused by ALS.
Beyond ACT for ALS, in June, the National Academies of Science, Engineering, and Medicine (NASEM) released Living with ALS, a groundbreaking report providing recommendations for key actions for the public, private, and nonprofit sectors to undertake to make ALS a livable disease within the next decade. The report was commissioned by NIH and developed independently by a NASEM committee of subject matter experts that included people with lived experience of ALS as well as researchers and health care providers. The report focuses on the experiences and needs of people with lived experience of ALS and provides recommendations for creating an integrated ALS multidisciplinary care and research system to facilitate earlier diagnosis, connect people to specialty care, and accelerate development of new therapies and prevention strategies.
People with lived experience of ALS have been and will continue to be actively involved in the implementation of all aspects of NINDS’s ALS efforts. They provide critical input and perspectives, and we are grateful for their expertise, engagement, and commitment. Through these collective efforts, we at NINDS have joined the fight against the relentless ALS clock, and we are working every day to try to slow it down, and hopefully someday, eliminate it completely.