Two Southern California University studies showed a reduction of neurodegenerative activity in amyotrophic lateral sclerosis (ALS) research models with each using a different treatment route. As reported in Inside Precision Medicine, the research teams were led by Justin Ichida Ph.D., stem cell scientist at USC.
ALS is also called Lou Gehrig’s disease in honor of the well-known Yankee Hall of Famer. Despite having ALS, in his farewell speech to his devoted fans he called himself the ‘luckiest man on the face of the earth.’
ALS, a neurodegenerative disease, is characterized by a fast progression that affects nerve cells in the brain and spinal cord (motor neurons). These nerve cells control the voluntary movement of muscles.
Paralysis and death may occur within five years after diagnosis. Effective treatments have yet to be developed due to this rare and fast-moving disease. Currently, two treatments, edaravone and riluzone, have been FDA-approved, but with limited efficacy.
Suppression of SYF2
A study recently featured in Cell Stem Cell used a biological database called a Connectivity Map which links drugs to genes and associated diseases. The team was trying to locate new potential treatments for a minor form of ALS. The map was created by Harvard and MIT’s Broad Institute.
Using the map, the researchers were able to identify the SYF2 gene. When this gene was suppressed in mice with ALS, their neurodegeneration, motor dysfunction, and other symptoms were reduced.
Yichen Li, a postdoc in the Ichida Laboratory, expressed enthusiasm for finding that the suppression of the SYF2 gene improved symptoms related to the TDP-43 protein. TDP-43 may become toxic. It is conceivably the cause of 97% of ALS cases.
As a result of these early studies, the scientists believe that the observed improvements are triggered by stimulating motor neurons that clear toxic proteins. The process, called exocytosis, moves fat-based bubbles to the cell wall and improves function. It also stops cellular breakdown.
About the Second Study
The second study inhibits a protein called (PIKFYVE) and had a beneficial effect on the cell lines of ALS, roundworms, fruit flies, and a mouse model of ALS. The team used the drug apilimod combined with RNA and genetic-based approaches.
Ph.D. student Michelle Hung of the Ichida Lab noted that they focused precisely on PIKFYVE and how it mitigates neurodegeneration, which is critical in developing new treatments.
In conclusion, Ph.D. Ichida acknowledged that the research is at the preclinical stage there is every indication that these two studies may lead to therapies that are more effective for people with ALS.
