BETHESDA, Md. (WDNews) — Scientists at the National Institutes of Health (NIH) have laid the groundwork for a potential gene-editing therapy to treat late-onset Tay-Sachs disease (LOTS), a rare genetic disorder that affects about 500 people worldwide.
The study, conducted in human cells and mice, showed that researchers were able to increase activity of the missing enzyme that causes LOTS, reducing symptoms and significantly extending lifespan in the mouse model. LOTS usually develops in late childhood or adulthood and can cause muscle weakness, loss of coordination, spasms, and sometimes cognitive decline.
The disorder stems from mutations in the HEXA gene, which limits production of beta-hexosaminidase A, an enzyme needed to break down fatty substances in the brain. Without enough enzyme activity, these fatty substances accumulate, damaging nerve cells in the brain and spinal cord.
“With LOTS, a slight correction will go a long way,” said Dr. Richard Proia of NIH’s National Institute of Diabetes and Digestive and Kidney Diseases. “This editing may only need to increase enzyme activity by about 10% to keep symptoms from getting worse and improve their quality of life.”
Scientists say the breakthrough is not yet a cure, but it provides a foundation for future human studies. Researchers are exploring delivery methods for the genetic edit that can cross the blood-brain barrier — a challenge for gene therapies — and avoid immune responses to viral delivery systems.
Dr. Cynthia Tifft of NIH’s National Human Genome Research Institute, another study author, noted that the research was strengthened by patient participation.
“It’s inspiring to work with someone who stays positive and engaged while this disorder robs them of control over their body. I’m motivated every day knowing that the work we’re doing matters,” Tifft said.
While additional studies are needed, researchers believe their progress may also apply to other lysosomal storage disorders, such as Sandhoff disease, Niemann-Pick disease, and Gaucher disease.
For more information about NIH research and ongoing clinical studies, visit www.nih.gov.
