Opioid Growth Factor Identified as MS Biomarker

A new study identified opioid growth factor (OGF) as a biomarker for the onset and progression of multiple sclerosis (MS).

Patricia L. McLaughlin, MS, DEd, a professor of neural and behavioral science at the University of Pennsylvania College of Medicine, said the research was prompted by studies showing that mice with an MS-like condition who were given exogenous treatment of OGF had improved movement and behavior, as well as longer periods of remission.

The treatment worked in mice with both the chronic and relapsing-remitting forms of the disease. Research also showed that treatment with low-dose naltrexone (LDN) to stimulate OGF production helped the mice.

McLaughlin told MD Magazine that the benefit of OGF therapy was demonstrated in numerous studies beginning in 2009, and the improvement seemed to happen both when the treatment was given at the start of the disease, and when it was given after the disease had already manifested.

“Hence we believed that OGF was dysregulated, and as part of the OGF-OGFr (receptor) axis unable to control (or repress) inflammatory cell proliferation,” McLaughlin said. “Thus we targeted OGF as a potential factor that was down-regulated or deficient in patients with MS.”

To test their hypothesis, McLaughlin and colleagues examined serum OGF levels in patients with MS and in mouse models. They found that patients with MS had lower OGF levels than healthy patients. In mouse models, they showed that lower OGF levels were associated with disease progression.

When mice were treated with LDN, their OGF levels returned to normal, while the same treatment had no effect on healthy models. It was already known that LDN treatments can improve quality of life and fatigue in MS patients, though the mechanism of the action was not understood until now.

McLaughlin said LDN is already used very widely in the MS community, but her research suggests it could play an important in limiting the disease’s progression.

“If given early enough following the diagnosis, one might be able to prevent substantial tissue damage--and thus reverse the downward progression of the disease,” McLaughlin said.

Other autoimmune disorders also seem to respond well to LDN, McLaughlin said, so it’s possible that OGF is a biomarker for those disorders as well.

More research is needed to understand LDN and OGF in MS patients, and to see if the research can be translated into earlier detection of MS, McLaughlin said. One limiting factor in her research was a lack of available data in humans.

“The challenge and difficulty is that MS patients are not required to bank blood samples and we were unable to control our human sample population — thus some patients may have MS for 4 years, others for 14 years,” McLaughlin said. “We have too few samples to know.”

She said OGF may be reduced in patients undergoing flares, for instance, but there aren’t enough human blood samples to be able to know for sure. There’s hope that MS patients will learn about the important research being done and volunteer to participate in clinical trials.

The study, “Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone” was published online in Experimental Biology and Medicine last month.