The causes of rare diseases can be difficult to uncover. A recent investigation by scientists at UT Southwestern involved over 1,200 participants and sought to find the gene responsible for a debilitating brain disease that causes blindness and paralysis, called neuromyelitis optica (NMO). The scientists are hopeful that their work, which was published in Nature Communications, will lead to good treatments for the disease. It also demonstrates the power that DNA storage banks have to inform our understanding of unusual disorders.
"This outcome shows that doing in-depth research pays off, and more studies like this may be needed to find the problem behind other rare conditions," said Dr. Benjamin Greenberg, an internationally recognized myelitis expert at UT Southwestern's Peter O'Donnell Jr. Brain Institute. "By taking a rare disease and doing more than just reading every third or fourth page of genetic code, we have modeled NMO in a much more accurate way."
Patients with NMO have a problem with their immune system that causes it to attack cells in the spine and optic nerve. While many of those affected are able to regain function with physical therapy and medication, many others are misdiagnosed. When the disease is not correctly identified, relapses and additional problems can happen, and it might be fatal.
By using whole-genome sequencing, the scientists uncovered a change in a gene that was linked to an increase in the risk of the disease. The gene makes a protein that attaches to antibodies; the protein can then interfere with what the antibody is bound to, which is often pathogenic microbes. In the NMO disorder, the antibodies improperly attach to places in the nervous system instead.
This genetic study could be considered along with clinical data to identify the patients that won’t benefit from typical treatments.
"Some patients go into remission and others don't, yet we haven't known why," Dr. Greenberg explained. "What we can do now is look at the DNA and determine if that has anything to do with why drugs are not working."
NMO is one of the least common autoimmune diseases that impact the spinal cord and brain. Because so few people are affected, it does not attract a lot of research attention. This work has demonstrated the value of researching rare disorders, however.
NMO is among several thousand rare diseases that cumulatively affect 30 million Americans yet individually don't involve large enough populations to attract widespread research efforts. As little as 0.3 percent of every one hundred thousand Americans have NMO - making it one of the most uncommon autoimmune diseases involving the brain and spinal cord.
"To target a disease as rare as this, to put this much technology behind trying to understand the disease - it hasn't been done before," Dr. Greenberg said. "This study has given insights into this condition that aren't just new but are distinctly different from other studies."