A study co-authored by UC San Francisco researchers offers the first evidence that a gene therapy technique involving ribozymes, molecules that disrupt protein production, can be used to slow neurodegeneration in an animal model, signalling a possible approach for overcoming one of the monumental hurdles of gene therapy.
In the study, reported in the August issue of Nature Medicine, researchers demonstrated that ribozymes could be used to reduce the production of a faulty gene product that leads to the degeneration of light-sensitive rod cells in the eye. The degeneration occurs in association with autosomal dominant retinitis pigmentosa, an untreatable condition of progressive blindness.
Importantly, the approach could potentially also be used to treat other diseases resulting from a destructive protein, including some forms of glaucoma, Huntington's disease, amyotrophic lateral sclerosis (ALS) and Warfan's syndrome, according to the senior author of the study, Matthew M. LaVail, PhD, a professor of anatomy and ophthalmology at UCSF.
The finding represents an important breakthrough in the still fledgling field of gene therapy, which has been particularly challenged by disorders caused by abnormal, or mutant, proteins, so-called autosomal dominant diseases, said LaVail.
Most gene therapy approaches have focused on diseases that occur when the two copies of a particular gene fail to produce, or fail to produce sufficient quantity of, a healthy protein. The challenge in developing treatments for these so-called autosomal recessive diseases, such as cystic fibrosis, has involved trying to introduce healthy genes directly into the pertinent cells to replace and compensate for the missing proteins. This challenge has been daunting enough. Some successes have been achieved in animal models with recessive diseases, but only in recent months have such approaches even begun to demonstrate small successes in clinical trials, according to LaVail.