La Spada, chief of the Division of Genetics in the Department of Pediatrics at UC San Diego School of Medicine, received a $900,000 award to further development of a treatment which blocks the gene mutation underlying SCA7. The research also may have implications for Parkinson’s disease, Huntington’s and amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, which are neurodegenerative disorders with similar types of genetic mutations.
The scholar award is given by the Harrington Discovery Institute at University Hospitals in Cleveland, which collaborates with various organizations to accelerate the development of promising research by physician-scientists. In particular, the funding helps researchers to bridge the gap from basic research to clinical application, known as the “Valley of Death,” which can keep innovative discoveries from advancing far enough to attract pharmaceutical drug development.
Dr. La Spada, also at Rady Children’s Hospital-San Diego, was one of three inaugural Gund-Harrington Scholars, named after Gordon Gund, founder of Foundation Fighting Blindness, a consortium of groups funding research in the area of degenerative retinal diseases.
“People with this disorder (SCA7) have trouble walking, talking, seeing – anything that requires coordinated movement,” said La Spada. “It can progress to the point that they can’t walk properly, need a cane, end up in a wheelchair and also can’t see. It’s a pretty horrible disease and affects numerous people, many of whom are teenagers or young adults.”
La Spada began his work on neurodegenerative disorders while in graduate school and drew national interest for his discovery of the cause of a neuromuscular disorder known as X-linked spinal and bulbar muscular atrophy, or Kennedy’s disease. He pinpointed a novel genetic mutation, resulting in the expansion of a triplet repeat of a nucleotide sequence, as the underlying cause. The finding represented a new type of genetic mutation and has now been implicated in other neurodegenerative diseases, including Huntington’s and ALS. “The mutation (expansion of a repeating sequence) is the same, but in each disease it involves a different gene,” he said.
In his work on SCA7, La Spada and colleagues created a mouse model in which they blocked the key SCA gene mutation using specialized gene-silencing technology. “We have found that we can rescue the vision of the mice,” said La Spada. In parallel studies, the researchers bred mice with the gene turned off at birth. “These mice were essentially OK, with no problems with movement control or vision,” he added. “The idea now is to continue this work in the hope that we can perfect it and bring it into human patients.” The goal is to launch a Phase I human clinical trial by the end of the three-year Gund-Harrington funding.
If the therapeutic strategy proves successful in SCA7, La Spada said he hopes it can also be tried in more common neurological diseases like Parkinson’s and ALS.