A path forward: strategic priorities for amyotrophic lateral sclerosis (ALS)

Neurodegenerative diseases progressively damage specific cells and connections in the brain and/or spinal cord, exacting an enormous toll on the health of people living with these diseases, as well as their families and caregivers. Amyotrophic lateral sclerosis (ALS) is a particularly devastating and complex neurodegenerative disease that affects the neurons that control voluntary muscle movement. People with the disease become progressively weaker and lose their ability to walk, talk, swallow, and eventually breathe on their own, with most people dying within 3-5 years of symptom onset. Four ALS therapies—three disease-modifying, plus one symptom-managing—have been approved by the Food and Drug Administration (FDA). Yet, to develop highly effective ALS treatments, we must address numerous challenges. Hope rests on treatments that are currently in development, or those that will follow based on the identification and validation of new therapeutic targets. Most appealing are treatments that might be instituted in those with genetic causes of ALS even before symptoms begin, or uncovering the still mysterious environmental factors that cause ALS.  

Last year, NINDS conducted a comprehensive and multifaceted process through a Working Group of the National Advisory Neurological Disorders and Stroke Council (NANDSC) to establish strategic priorities for the ALS research community. Comprised of scientists, clinicians, people living with ALS, people with genetic risk for ALS, and caregivers, and co-chaired by Drs. Rita Sattler and Robert Brown, the working group explored the landscape of ALS and engaged the ALS community. The culmination of their work has been the development of draft priorities(pdf, 1818 KB) for accelerating research on the biology behind ALS, translating fundamental research into potential ALS therapies, optimizing ALS clinical research, improving the quality of life of persons living with ALS and caregivers, and identifying opportunities for collaborations and partnerships. Yesterday, the NANDSC voted to endorse the draft research priorities presented by Drs. Sattler and Brown, which identifies the most promising priorities for research that may lead to the discovery of effective interventions for the diagnosis, treatment, management, prevention, or cure of ALS.

I am grateful and humbled by the invaluable perspectives from people with lived ALS experiences that were shared with us throughout the strategic planning effort. The strategic plan benefited greatly from their real-world perspectives and experiences. Early in the process, NINDS sought nominations for people living with ALS, caregivers, advocates, and pre-manifest ALS gene mutation carriers - to be a part of the working group’s steering committee and subgroups focused on individual topics. NINDS also sought input from ALS community members and the public through an initial Request for Information (RFI)(pdf, 180 KB) that informed the working group. The working group presented draft priorities at an open two-day workshop that included multiple public comment periods with thoughtful discussions, and a second RFI for feedback on the draft priorities provided an additional opportunity for ALS community members to provide input. This engagement and the experiences and insights shared by the ALS community greatly enhanced and strengthened the Working Group’s efforts and recommendations.

The Co-Chairs’ report to the NANDSC yesterday highlighted the urgency for progress in ALS research. The disease often occurs with no clearly associated risk factors and no family history of ALS.  Given the typical survival time after symptom onset, the clock is ticking, and quickly. The field must understand the molecular basis of clinical heterogeneity in ALS and improve methods for following the trajectory of the disease course, from pre-symptomatic to late symptomatic phases. In tandem with these fundamental biology efforts, clinical therapies should be initiated as early as feasible, including when the earliest symptoms appear. In addition, repositories to collaborate on research tools, protocols, and biospecimens, and other resources will be immensely valuable. The entire ALS community must develop collaborative, openly accessible research infrastructures, bringing together all the valuable data, so it is accessible for exploration by scientists around the world. The field could greatly benefit from the acquisition of multidimensional data, collected longitudinally and harmonized to permit data sharing.

It is also especially clear to me that attending to quality of life (QOL) in ALS is of paramount importance, as is improving access to information about ALS and options for participating in clinical research and therapeutic trials. As I listened to yesterday’s report, an underlying theme was the powerful concern that we must understand the impact of ethnic diversity, race, gender, socioeconomic factors, and geographical location (e.g., rural communities) on all aspects of ALS, such as the timeliness and efficacy of therapy.

We will now work to address these new strategic priorities in several ways, including through existing and future funding opportunities supported by NINDS and other NIH Institutes and Centers. Our hope is that a portfolio of diverse funding mechanisms will attract and support research by individual investigators and research teams and promote collaboration across academia, the pharmaceutical and biotechnology industries, and patient advocacy groups. These activities will join recent NINDS and NIH efforts, including the Accelerating Leading Edge Science in ALS (ALS2) initiative and especially the launch of the Critical Path for Rare Neurodegenerative Diseases (C-Path), announced by the NIH and the FDA as a public-private partnership aiming to advance the understanding of neurodegenerative diseases and foster the development of treatments for ALS and other rare neurodegenerative diseases. NINDS and FDA are also especially excited to work with colleagues at the Foundation for NIH and C-Path to expand the FDA-NIH public private partnership for rare neurodegenerative diseases to include efforts that will collect natural history data, acquire, and analyze biospecimens, bioimaging, and other test results. The goal is to facilitate many ongoing and future efforts to enable the identification of biomarkers to diagnose ALS as early as possible, to gauge disease progression, and to discover new targets for highly effective therapies.

In addition, the NIH Congressional Appropriation for Fiscal Year 2023 includes $75 million for the Accelerating Access to Critical Therapies for ALS Act, which will allow continued support for an NIH grant program to fund ALS research utilizing expanded access for investigational drugs or biological products for individuals who are not otherwise eligible for clinical trials in ALS. We urge the ALS community to communicate this expanded access research opportunity to investigators and industry contacts. Webinars to provide technical assistance are scheduled for February 15 and 22, 2023; interested applicants can pre-register to attend.

Guided by new strategic priorities and through these collective efforts, we have a path forward to advance our understanding of what triggers ALS, what drives its rapid progression, and how we can leverage that knowledge to develop more effective treatments and better the lives of people living with ALS and their families.