Spurring innovative research toward ALS cures through Accelerating Leading-edge Science in ALS (ALS2)

Spurring innovative research toward ALS cures through Accelerating Leading-edge Science in ALS (ALS2)

A schematic of two neurons communicating with one another, against a dark background. Where the neurons are connected at the synapse, there is a white circle, indicating electrochemical activity.Neurodegenerative diseases result from progressive damage to cells and connections in the brain, spinal cord and nerves, impairing a person’s ability to move, think, communicate, or feel, and often ultimately lead to death. These diseases exact an incalculable personal toll and a tremendous economic cost in medical expenses and lost productivity. Amyotrophic lateral sclerosis (ALS) is a particularly devastating 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, move, swallow, and even to breathe on their own. 

For people with neurodegenerative diseases and their families, cures can’t come soon enough.  ALS has no known cure, and it is often rapidly fatal, with a median survival time of just 20 to 48 months. Currently FDA-approved therapies extend life by only a few months and do not improve symptoms. While ALS is likely to involve a combination of genetic and environmental risk factors, in most cases, its underlying cause is not known. Indeed, the biggest hurdle to developing effective interventions to prevent or treat ALS is our incomplete understanding of its complex causes, what drives its progression, and factors that could be modulated to recover function. Overcoming these obstacles warrants investigating highly innovative concepts and applying powerful new technologies that draw from a variety of scientific disciplines and perspectives. Pursuing innovative or unconventional ideas can be risky, but the potential payoffs for people with ALS are well worth the risks.  

To solicit and support such high-risk, high-reward ALS-related research, NINDS is participating in the Accelerating Leading-edge Science in ALS (ALS2) initiative, a partnership between the NIH Common Fund and four NIH Institutes: the National Institute on Aging (NIA), the National Institute of Environmental Health Sciences (NIEHS), the National Institute of General Medical Sciences (NIGMS), and NINDS. NIH is investing approximately $25 million over 5 years in this program to spur innovative research on ALS. ALS2 is part of the NIH Common Fund’s High-Risk, High-Reward (HRHR) research program, through its Transformative Research Award initiative. ALS2 is taking a three-pronged approach to improve our understanding of ALS:

  • Emerging Technologies from Multiple Fields: Adapting emerging tools and technologies from neuroscience and cell biology to identify what causes ALS at the molecular level, and how the disease progresses, leading to new therapeutic strategies.
  • Attracting New Talent from a Diversity of Scientific Disciplines: Solving the complex nature of a disease like ALS requires a concerted effort by scientists from not only neuroscience and neurology but also from cell biology, bioengineering, chemistry, biophysics, genomics, environmental health science, and computational science.
  • Understanding Disease Convergence: ALS is the most common motor neuron disease, but clues to its biology may come from discoveries in other neurodegenerative conditions. Understanding the overlap in the biology among these conditions, together with the intensive research underway on neurodegeneration in general, may provide important clues for the triggers and rapid progression of ALS.

The initiatives of the Common Fund’s High-Risk, High-Reward Research (HRHR) program are a time-tested, powerful approach to spark innovation in biomedical and behavioral science. Over the last decade, the HRHR program’s Transformative Research Awards have provided a platform for individuals or teams proposing projects that are inherently risky and untested but have the potential to create or overturn fundamental paradigms. ALS2 has leveraged this platform and reviewed proposals with an emphasis on the strength of their conceptual framework, their level of innovation, and their potential to significantly advance our understanding of ALS. Although the research ideas themselves are bold and pursue new ways to examine ALS, study protocols do not carry additional risk for study participants. This approach could be a gamechanger for ALS research, and I am excited about the awards that were recently announced for ALS2:

The answers to ALS will take time to uncover, but through the ALS2 initiative, we hope to dramatically advance our understanding of what triggers ALS and what drives its rapid progression. Elucidating these underlying mechanisms will be a critical step toward testing potentially more effective therapeutics that are so needed to treat this tragic disease.

Tuesday, October 5, 2021