Scientists conducting one of the largest full DNA analyses of a rare
disease have identified a gene mutation associated with a perplexing
brain condition that blinds and paralyzes patients.

A UT Southwestern study that used genetic data from more than 1,200
participants may help scientists improve treatments of neuromyelitis
optica (NMO). More broadly, the research demonstrates the potential of
utilizing large DNA banks to better understand and treat other diseases
that have not undergone full genetic sequencing.

“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 with 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.”

NMO is a potentially fatal disease in which the immune system attacks
cells in the optic nerve and spinal cord, leaving some patients blind
and/or paralyzed. Patients can recover most of their function through
medications and physical rehabilitation, though many are misdiagnosed
with multiple sclerosis and face a higher risk of relapse and permanent
damage due to lack of proper therapy.

The study published in Nature Communications shows that a variation in a complement component gene
was associated with an increased risk of developing NMO. The gene
produces a protein that binds to antibodies and can damage whatever the
antibody is attached to, usually harmful bacteria. But in the case of
NMO, the antibodies stick to parts of the nervous system.

The identification of the genetic variation, combined with clinical
trial data, may help scientists determine in advance which patients
won’t benefit from standard treatment.

“Some patients go into remission and others don’t, yet we haven’t
known why,” Dr. Greenberg said. “What we can do now is look at the DNA
and determine if that has anything to do with why drugs are not

The O’Donnell Brain Institute is one of only a few sites in the U.S.
that specializes in treating NMO. It is also one of two centers in the
country focused on transverse myelitis, including the acute flaccid
myelitis that attracted national headlines in recent years after at
least 200 children became paralyzed. Dr. Greenberg has led long-term
efforts to collect biologic samples from myelitis patients in hopes of eventually developing treatments that better target these diseases.

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 100,000 Americans have NMO – one of the most uncommon
autoimmune diseases involving the brain and spinal cord.

Dr. Greenberg said the new study validates efforts to more closely
analyze the genetics behind other rare diseases. He notes that the
research clarifies previous findings about NMO’s genetic underpinnings,
derived from studies that analyzed only a portion of the genome.

“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.”

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