Leigh syndrome associated with mutations in the SURF1 gene severely disables affected children. At the basic mechanism level, the brains of children lacking this gene cannot generate adequate energy for proper functioning of the brain. Unfortunately, there is neither cure nor treatment for the disease. In the present day and age, doctors can diagnose this easily, know its precise cause (missing SURF1 function), but have nothing to offer these children and families.
The goal of this project is to replace the missing SURF1 gene in the children suffering from its absence. The gene replacement is carried out using a special virus called AAV9. This virus is a safe virus that normally lives within us humans. The SURF1 gene is packaged in the virus, and the virus delivers the gene to brain cells.
As a first step, we need to show that this is feasible and safe in the mouse model of the disease, i.e. in mice likewise lacking the same gene. This pre-clinical work (mouse experiments) will entail:
Establishing a colony of SURF1 deficient mice in our laboratory.
Assessing for safe and efficacious delivery of the viral vector and the SURF1 cargo to the mouse central nervous system.
Assessing the effectiveness of the treatment in the mouse. Specifically, we will test whether the brain energy metabolic defect that results from absence of SURF1 is corrected, at least in part, in the mice receiving the gene replacement.
Once we show that the treatment works, even if partially, in the mouse model of the disease, and does not cause harm, we will obtain permission from the Food and Drug Administration to initiate a human clinical trial. If successful, children and families afflicted with this terrible disease will no longer be told ' there is nothing I can do for you', but instead be told, 'SURF1 deficiency, OK, here's what we're going to do...'
The Research Team