Oklahoma Medical Research Foundation scientist Bob Axtell, Ph.D.

Scientists at the Oklahoma Medical Research Foundation have broken new ground in developing biomarkers for a rare autoimmune disease.
Performed in collaboration with scientists in Germany and a trio of American universities, the new research could dramatically improve treatment strategies for patients suffering from neuromyelitis optica, or NMO.
“For the first time, we’ve been able to discern NMO prognosis using molecular markers,” said OMRF scientist Bob Axtell, Ph.D., who led the study. “This could help doctors tailor more effective courses of therapy to individual patients.”
NMO occurs when the immune system attacks its own optic nerves and spinal cord, resulting in inflammation that can cause severe pain and vision loss. In some instances, NMO can invade regions of the brain or the brain stem.
The illness affects about 4,000 Americans, 80 percent of whom are women. Over time, patients typically develop blindness, muscle weakness and paralysis.
Until recently, physicians have been hamstrung by a lack of treatment options. But according to Axtell, “The FDA approved a drug for NMO and others drugs should be available soon.”
In the new research, published in the journal Nature Communications, scientists examined new biomarkers for the disease, hoping that they could help instruct physicians on patient prognosis and response to therapy.
Namely, they looked at interferon, which is a naturally occurring protein made by the body during inflammation. Interferon appears at elevated levels in patients suffering from NMO. Meanwhile, patients with multiple sclerosis (MS), which shares many symptoms with NMO, have low levels of this protein and MS patients require supplemental interferon treatment to bring levels back to normal.
“We’ve always been interested in the effect of interferon and why it improves MS symptoms and makes NMO symptoms worse,” said Axtell.
The researchers assessed gene-expression and protein markers in the blood of NMO patients with severe symptoms compared to NMO patients with more mild symptoms. “We found that interferon genes and proteins are elevated in subsets of NMO patients who experience a severe form of this disease,” said Axtell.
“The ability to use molecular signatures to stratify NMO patients into different groups may allow doctors to predict the prognosis of individual patients and help develop personalized approaches to treat this devastating disease,” said Axtell.
Co-lead investigator Friedemann Paul, M.D., from the Max Delbrück Center for Molecular Medicine in Berlin, Germany, said identifying a link between interferon levels and disease disability might pave the way for new clinical tests for prognosis and treatment of NMO.
“NMO is a rare and often devastating disease, and there is considerable anxiety in patients with regard to disease course and future disability,” said Paul. “To date, there is a lack of biomarkers that can help neurologists to predict disease course and treatment response. The findings of this study suggest that interferon signatures could be used to devise clinical tests for prognosis and treatment response in NMO.”
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The collaboration also included scientists at the University of California-Irvine, University of Michigan, and University of Oklahoma Health Sciences Center.
In addition to Axtell, other OMRF scientists who contributed to the findings were Agnieshka Agasing, Ph.D, Bhuwan Khatri, Ph.D., Saurabh Gawde, Gaurav Kumar, Ph.D., James Quinn, Ph.D., Rose Ko, Ph.D., and Christopher Lessard, Ph.D.
The National Institutes of Health (R01AI137047 and R01EY027346) and the National Multiple Sclerosis Society (RG-1602-07722) provided funding for Axtell’s work.