Miguel Sena-Esteves, PhD, associate professor of neurology at the University of Massachusetts Medical School, was presented with the annual "See the Light" award from the Mathew Forbes Romer Foundation (MFRF) in recognition of his work for leading the fight against children's genetic diseases of the brain.
A member of the Gene Therapy Center at UMass Medical School, Dr. Sena-Esteves is investigating the potential of using gene therapy techniques to replace the faulty gene that causes Tay-Sachs Disease, a devastating neurological disorder that causes deterioration of mental and physical abilities starting at six months of age and usually results in death by the age of five. He was a leading force behind the creation of the Tay-Sachs Gene Therapy Consortium, an international collaboration of scientists committed to translating current gene therapy results into a human clinical trial within the next three years.
"Research for many degenerative neurological diseases, such as Tay-Sachs, wouldn't be possible without support from patient and family advocacy groups such as the Mathew Forbes Romer Foundation," said Sena-Esteves. "Backing from the MFRF has been critical to the formation of the Tay-Sachs Gene Therapy Consortium and the success of our research. It is an honor to have them recognize our work with this award."
Tay-Sachs is one of 40 rare, inherited metabolic disorders called lysosomal storage diseases that result from a breakdown in a cell's ability to remove or recycle waste products due to a missing enzyme. The gradual build up of waste eventually results in cell death and causes the slow breakdown of motor and neurological function in patients.
Tay-Sachs is most common in Eastern European people of Jewish descent, also known as Ashkenazi Jews. People of Cajun, French-Canadian, and Irish descent are also at higher risk for this devastating disease. It's estimated that the occurrence of the recessive gene responsible for Tay-Sachs in the Ashkenazi community is 1 in 27 compared to 1 in 50 in people of Irish descent and 1 in 250 in the rest of the population. Patients with the disease must inherit the recessive form of the gene from both parents.
Though genetic screening has greatly reduced deaths from Tay-Sachs, approximately 25 to 30 individuals die from the disease annually.
Sena-Esteves and his colleagues at the Tay-Sachs Gene Therapy Consortium are using a recombinant adeno-associated virus (rAAV) vector to replace the faulty gene that produces the enzyme responsible for removing and recycling waste products in cells. Once introduced into brain, the functioning gene begins making the missing enzyme, turning parts of the brain into mini-factories. Capitalizing on the natural pathways of the brain, those enzymes are then distributed throughout the brain, allowing cells to resume their natural metabolic functions and remove waste products.
"As we learn how to do gene transfer effectively in the brain, we open up the possibility to a lot of other neurological diseases," said Sena-Esteves. "In our minds, what ultimately matters is the ability to deliver a potential treatment to the children suffering from this horrible disease. Ultimately, that's what drives us all."