Development of AAV-Mediated SOD1 Gene Silencing Therapy in ALS

Research Summary

Principle Investigators: Robert Brown D.Phil., MD & Merit Cudkowicz MD

About 10% of ALS cases are familial. Most of the known genetic defects in familial ALS act by triggering one or more toxic processes that impair the viability of motor neurons, leading to motor neuron death. This project will use viruses to introduce reagents into the brain and spinal cord that block the mutant genes from triggering toxicity. This is accomplished by turning off the activity of those genes using new technologies for so-called “gene silencing.” The viruses are used to penetrate the blood-brain barrier to deliver the gene-silencing reagents, which then inactivate the genes in question. This technology will be tested first in cases of ALS arising from mutations in well-defined ALS genes (e.g., SOD1 and C9orf72). This project is intended to take the gene silencing all the way to a pilot human trial. We are hopeful that in the long term these studies will lead to a general platform or method for treating other types of familial ALS and potentially some cases of non-familial ALS as well.


Massachusetts General Hospital
Merit Cudkowicz MD
James Berry MD

University of Massachusetts Medical School
Robert Brown D.Phil., MD