Rare Disease Research Hits Home for Scientist
Eureka Staff

Rare Disease Research Hits Home for Scientist

What happens when a scientist learns that the gene she studies is the root of her daughter's devastating illness. The New York Times article chronicles this rarest of odds.   

It’s not that unusual for people affected by rare diseases to make radical changes in their life’s work. Non-scientists start disease foundations, fly halfway around the world to consult with scientists or take to Google to track down other cases. In one instance, Eric Minikel and Sonia Vallabh, a couple who changed careers and became scientists after they received a genetic testing report showing that Sonia had inherited a fatal genetic mutation in the prion protein gene.

But what if you were a scientist studying the FOX family of genes, only to find out that your 2-year-old daughter had one of these exceedingly rare mutations. Pam Belluck’s article in the New York Times describes how Oregon Health and Science University scientist Soo-Kyung Lee’s brain research focusing on the FOX family of genes became personal overnight after doctors determined that the reason her daughter Yuna had seizures, cried uncontrollably and couldn’t walk, talk or stand, was likely due to a mutation in the FOXG1 gene. Yuna, it turned out, had one dysfunctional and one functional FOXG1 gene, producing half the necessary FOXG1 protein to allow her brain to develop normally. Because harmful FOXG1 mutations are exceedingly rare and usually not inherited—the gene mutates spontaneously during pregnancy—Lee and her husband, Jae, also a genetics professor at OHSU were dumbfounded by the news.

Lee’s research, with the help of her husband, Jae, is now focused exclusively on studying how the FOXG1 gene works and why mutations like Yuna’s are so devastating. One of the areas she is curious about is possibly developing a gene therapy that would cause the functional FOXG1 gene to produce more protein. While researchers are doubtful this strategy would work in Yuna’s case, gene therapy nonetheless remains a hot area in rare disease research today.

At a recent symposium sponsored by Charles River, Guangping Gao, Professor and Director of the Gene Therapy and Vector Core at the University of Massachusetts Medical School, described how his group is using recombinant human adeno associated viruses (AAVs) to try and cure Canavan’s disease, a fatal condition triggered by a mutated version of a gene called ASPA passed on by both parents. The dysfunctional gene prevents the clearing of N-acetyl aspartic acid from the brain, and as the acid builds up it begins eating away at the myelin that insulates our brain neurons, turning it into a spongy mess. Gene therapy is also being explored in many other rare diseases, from Huntington’s disease, to extremely rare diseases like Niemann-Pick Disease, Type C, Pompe disease and spinal muscular atrophy.