A team of experts, led by scientists at the Harvard Medical School (HMS), announce the discovery of the gene responsible for triggering a very devastating type of early-onset blindness, called Leber congenital amaurosis (LCA).
The discovery could lead to the development of new therapies and drugs aimed at addressing this gene, called NMNAT1. Now that scientists know what they need to address, they can start work on gene therapies that would prevent NMNAT1 from causing LCA in patients.
The condition does not have a high incidence in the general population, but it causes blindness in the vast majority of cases. To make matters worse, LCA mostly affects infants during their first few months of life, triggering a type of manifestation called nystagmus.
This is characterized by unusual, roving eyes, and by a lack of visual responsiveness to external stimuli. Over time, the problem advances, until the children eventually lose their eyesight completely. In some patients, this is accompanied by symptoms affecting other organs, but that is relatively rare.
Scientists from the Children's Hospital of Philadelphia and the Loyola University Chicago Health Sciences Division were also a part of the new investigation, details of which were published in the July 29 online issue of the top scientific journal Nature Genetics.
“The immediate benefit of this discovery is that affected patients with mutations in this new LCA gene now know the cause of their condition,” explains a co-senior author of the study, expert Eric Pierce.
“Scientists now have another piece to the puzzle as to why some children are born with LCA and decreased vision. The long-term goal of our research is to develop therapies to limit or prevent vision loss from these disorders,” he goes on to say.
Pierce holds an appointment as an HMS associate professor of ophthalmology, and is based at the Massachusetts Eye and Ear. He explains that NMNAT1 is the 18th LCA gene ever discovered. It was found in a “suspicious” region of the genome.
Experts knew that this area held a gene involved in LCA, but they were unable to determine precisely which of them played the major part. The effort to find it began in 2003, and lasted 9 years.
Interestingly, NMNAT1 is “a gene that no one could have predicted would be associated with LCA,” Pierce adds.
“With the robust database and pipeline that we have developed, we have analyzed more than 300 whole exomes of patients and families with single-gene diseases,” says the other co-senior author of the paper, investigator Xiaowu Gai.
“We are following up on a number of strong candidate genes. We are sequencing many new samples and expect similar exciting discoveries for other diseases,” adds the scientist, who is the director of the Center for Biomedical Informatics at Loyola University Chicago Stritch School of Medicine.