Development of a novel therapy for Amyotrophic Lateral Sclerosis (ALS)

In ALS, several genes have been identified that, when altered, can contribute to disease. For people living with SOD1-ALS, a pathogenic variant in the SOD1 gene causes the SOD1 protein to become misfolded and toxic, driving motor neuron damage. A recently approved treatment for SOD1-ALS, called Qalsody, works by stopping the production of the SOD1 protein altogether in the brain. Although this therapy is a major breakthrough for this type of genetic ALS, it is important to optimize treatments for SOD1-ALS by reducing side effects and finding better ways to delivery therapies.

In this project, Dr. Kong and team aim to address SOD1 toxicity in a different way by using a therapeutic molecule called CT4-CTM, which intends to target only misfolded SOD1 protein, while leaving healthy versions intact.

Because delivering this specific therapy directly to the brain and spinal cord would be challenging, the research team is attempting a gene therapy approach that aims to produce CT4-CTM in neurons after a single injection into the bloodstream. The study will test how well this therapeutic approach clears toxic SOD1 in a mouse model of ALS, and whether it can slow or prevent ALS symptoms. ALS Canada and Brain Canada previously supported testing CT4-CTM, without the gene therapy approach, in the same mouse model with a 2015 Arthur J Hudson Translational Team Grant, yielding a publication in 2023.

Learn how early funding from the ALS Canada Research Program contributed to the discovery of the SOD1 gene in our Driving Discovery series.

Dr. Jiming Kong is a Professor in the University of Manitoba, where he has dedicated over two decades to researching neurodegenerative diseases, with a primary focus on ALS.

His research work began with a landmark paper in 1998 demonstrating that massive mitochondrial degeneration in motor neurons triggers ALS onset in mutant SOD1 mouse models, a finding that helped shape early understanding of ALS pathology. His recent studies explore misfolded and oxidized SOD1, mitochondrial dysfunction, and innovative approaches like selective removal of misfolded SOD1 to delay disease onset, as well as links between ALS-linked mutations and accelerated aging.

Deeply connected to the ALS community, Dr. Kong serves on the Board of Directors of the ALS Society of Manitoba since 2016, where he actively contributes to patient advocacy, public education, and support initiatives for those affected by ALS in the province. His research bridges molecular mechanisms to potential treatments, and he is passionate about translating discoveries into real hope for people living with ALS.