The National Institutes of Health is committed to advancing research on amyotrophic lateral sclerosis (ALS). There is currently no cure for ALS although FDA-approved drugs are available to treat ALS symptoms or slow ALS progression. NIH funds a wide spectrum of research to improve our understanding of ALS to inform the development of more effective treatments.
During FY23, NIH has made strides to implement the Accelerating Access to Critical Therapies for ALS Act (ACT for ALS), which was signed into law by President Biden on December 23, 2021 to support advances in ALS.
Section 2 of ACT for ALS requires the Secretary of HHS to establish a grant program for research using data from expanded access to investigational drugs for individuals not otherwise eligible for ALS-related clinical trials. NIH has made three new awards for this grant program:
“An Intermediate-Size Expanded Access Protocol for Amyotrophic Lateral Sclerosis with Pridopidine” (U01NS136021): This study, led by the small business Prilenia Therapeutics Inc. and researchers at Massachusetts General Hospital, will investigate pridopidine, a small molecule drug that activates the Sigma-1 receptor, which is found on neurons and has been linked to ALS in genetic and preclinical studies. The team plans to enroll 200 people living with ALS across 45 clinical sites in the U.S. As part of this study, researchers will obtain real world efficacy data, develop remote assessments of speech, identify disease biomarkers, and compare differences in clinical outcomes to various versions of the Sigma-1 Receptor gene.
“Intermediate-size Expanded Access Protocol for CNM-Au8 in Amyotrophic Lateral Sclerosis (ALS)” (U01NS136023): Researchers from the small business Clene Nanomedicine and Columbia University will test the safety and efficacy of CNM-Au8 in 100 people living with ALS across 10 clinical sites and a virtual clinic by Synapticure. CNM-Au8 is an orally administered suspension made of gold nanocrystals that may protect neurons by raising levels of energy molecules in cells. In this study, researchers will also measure changes in three plasma-based biomarkers of disease progression, develop novel tools for patient recruitment to increase access for people traditionally underrepresented in clinical research and expanded access programs, and use machine learning along with other approaches to predict disease progression.
“Intermediate-Size Expanded Access Trial of Autologous Hybrid TREG/Th2 Cell Therapy (RAPA-501) of Amyotrophic Lateral Sclerosis” (U01NS136020): This study, led by the small business Rapa Therapeutics, LLC and researchers at Massachusetts General Hospital, will investigate RAPA-501, a cell therapy that is designed to reduce inflammation, which may slow disease progression. The team plans to enroll 40 people living with ALS across 7 clinical sites to look at immune system activity and use standard methods and machine-learning based algorithms to examine treatment efficacy.
Section 3 of ACT for ALS establishes a Public-Private Partnership (PPP) for Rare Neurodegenerative Diseases between NIH, FDA, and other eligible entities. NIH and FDA are collaborating to establish this partnership, which has three integrated components: 1) the Critical Path for Rare Neurodegenerative Diseases, which was announced by NIH and FDA in 2022; 2) a Clinical Research Consortium, which was established in 2023 to collect clinical data and samples considered critical to the work of the PPP; and 3) a partnership facilitated by the Foundation for NIH (FNIH) that will be announced soon.
Two awards have been issued for Coordinating Centers for the ALS Clinical and Expanded Access Research Consortium, which will include sites across the country, including in underserved areas:
People with lived ALS experience, including people living with the disease, caregivers, and people with genetic risk for the disease, have been critical partners in all of these efforts. People with lived experience served on review panels for the expanded access grants. In addition, people with lived experience are participating in and providing valuable input to the PPP serving on every working group and committee from the very beginning.
To learn more about ALS-related research efforts at the NIH’s National Institute of Neurological Disorders and Stroke, please visit the Focus on ALS page.