New ALS discovery at Western University

May 14, 2024 – Researchers led by Dr. Michael Strong at Western University in London, Ontario, revealed new data that describes a possible future treatment avenue for ALS. Dr. Strong is a world-renowned scientist and clinician in ALS and one of the key individuals who first focused on the disease in Canada.

In this study, published yesterday in the peer-reviewed journal Brain, Dr. Strong’s team describes a protein called NF242, designed to interact with another important protein in ALS called TDP-43. The function of TDP-43 is abnormal in 97% of people with ALS, making it a potentially critical target to normalize for treatment. The global ALS field is currently working to understand what aspect of TDP-43 could lead to ALS, and these experiments focus on the theory that TDP-43 forms abnormal structures that are toxic to our motor neurons, the living wire-like cells that connect our brain to our muscles.

About a decade ago, the Strong lab discovered a protein called RGNEF that binds very specifically to TDP-43 in ALS and wondered if they could use it as a mechanism to prevent TDP-43 toxicity. Using fruit flies and mice that are genetically created to get ALS-like disease, the scientists tested what would happen if these animals also created a piece of the RGNEF protein called NF242. The fruit flies with NF242 moved and survived remarkably better than those without. Mice making NF242 also performed better, living on average a few weeks longer and delaying ALS-like symptoms.

These results represent a first step in determining if NF242 might be of value in ALS. Any potential treatment targeting TDP-43 is exciting as it would be more scientifically aimed at what many believe could be the underlying biology of ALS than the numerous, less specific treatments tested in clinical trials to date. It is also important to note that laboratory treatments demonstrating an ability to slow disease in animal models of ALS are not unprecedented; they are discovered and published multiple times each year. So far, they have largely failed to translate to benefit in people. Many of these treatments are further along in testing, and some are already in clinical trials.

Dr. Strong has stated his commitment to pushing NF242 toward the clinic as fast as possible but also explains in the manuscript that more optimization may be necessary to determine the best version suitable for human clinical trials. While that process can often take years, this discovery provides a new addition to the list of promising future therapeutic avenues that we can remain cautiously optimistic about while contributing new knowledge to our understanding of ALS.