Overcoming the Complexities With Gene Therapy in ALS: Anna Underhill, BS

WATCH TIME: 3 minutes

"One of the things is difficulty accessing the brain cord, the brain and spinal cord. Any treatment that you have has to get into the spaces where the cells are so they can actually help. For ALS, at the moment, there’s a small number of targets that we can target therapeutically at the moment, which is why we need this research into ALS proteins that could also be used as potential targets."

For approximately 90% of all cases of amyotrophic lateral sclerosis (ALS), there is no known family history of the disease or presence of a genetic mutation linked to the disease. Although, for the remaining 5% to 10%, there is a known family history of the disease that has opened the door for gene therapy, a targeted approach that can potentially fix or block the negative effects of coding errors. Some of the most promising gene-therapy–based approaches for ALS to date include antisense oligonucleotides, RNA interference, or gene editing technology such as CRISPR.

With close to 40 different genes discovered that are linked to the disease, the main issue is now validating the genes. One of these, SARM1, a variant thought to promote neuron death, is also being evaluated by several researchers from King’s College London. The project will use stem cells converted to neurons in a laboratory to firmly establish a causative role for the variant, as well as manipulate the cell culture environment and other genes to identify risk factors interacting with it.

There are several reasons why the research has not translated to therapeutic success, says Anna Underhill, BS, an investigator of the project. Underhill, a postdoctoral researcher at King’s College London, sat down with NeurologyLive^® to discuss the complexities of gene therapy, where the lag stems from, and the future directions of her study. She also provided detail on the uniqueness of SARM1 mutation, including a possible compensatory mechanism in the cell.