Restoring Neuregulin-1 beta 1 Protein Levels May Help Halt MS Progression

Patricia Inacio, PhD avatar

by Patricia Inacio, PhD |

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Neuregulin-1 beta 1 protein

The levels of a protein called Neuregulin-1 beta 1 (Nrg-1beta1) decline with the onset and progression of multiple sclerosis (MS), a new study suggests.

The findings support the potential of Nrg-1beta1 as a predictor of MS risk and progression and suggest that restoring its levels may help halt disease progression.

The study, “Neuregulin-1 beta 1 is implicated in pathogenesis of multiple sclerosis,” was published in the journal Brain.

MS is characterized by the loss of myelin — the protective coat surrounding nerve fibers — due to a mistargeted immune reaction. The mechanisms underlying the onset of MS, however, are still poorly understood.

Now, a team led by researchers at the University of Manitoba, Canada, discovered that the levels of a particular protein, called Nrg-1beta1, decline with MS onset and progression.

Using the experimental autoimmune encephalomyelitis (EAE) mouse model, a well-established model for human MS, the researchers found that the levels of Nrg-1beta1 declined within spinal cord lesions as well as in the blood and spleen before the animals showed symptoms (pre-symptomatic stage). That decline continued as the disease progressed.

The levels of Nrg-1beta1 also were found to be significantly reduced in people with early MS, and its reduction was associated with the development of relapsing-remitting MS (RRMS).

“We have shown that a decline in the plasma levels of Neuregulin-1 beta 1 is positively associated with MS development and progression, and could be potentially used as an early disease marker to help in MS diagnosis,” Soheila Karimi, PhD, senior scientist at the regenerative medicine program in the Max Rady College of Medicine and the study’s senior author, said in a press release.

“This is an important observation because there is currently an unmet need for early disease markers for MS. This could lead us in the future to predicting whether someone may develop the disease,” Karimi added.

Restoration of the levels of Nrg-1beta1 while MS is developing was sufficient to delay the onset of the disease and ease the effects of disease progression and severity in the MS mouse model.

Of note, therapeutic restoration of Nrg-1beta1 showed positive effects when given as a preventive treatment — prophylactically — before symptoms began, and also upon symptoms, known as symptomatically, and both acutely and chronically.

According to the team, Nrg-1beta1 exerted its therapeutic benefits not by suppressing the immune system but rather by balancing it out. Specifically, Nrg-1beta1 lessened the infiltration of certain immune cells into the central nervous system (CNS), comprised of the brain and spinal cord. Moreover, Nrg-1beta1 promoted the increase of immune cells that repair and help control the immune system in the MS mouse model.

“Taken together, our new findings in multiple sclerosis and experimental autoimmune encephalomyelitis have uncovered a novel regulatory role for [Nrg-1beta1] early in the disease course and suggest its potential as a specific therapeutic target to ameliorate disease progression and severity,” the researchers wrote.

“We are hoping that we can use this study as a foundation to build on and hopefully at some point translate these discoveries into clinical therapies,” Karimi said.

The study was supported by funding from the MS Society of Canada, Diagnostic Services Manitoba, and the Canadian Institutes of Health Research.

The team has received new funding from the MS Society of Canada to investigate the levels of Nrg-1beta1 in a larger number of MS patient samples and to assess the potential of restoring Nrg-1beta1 as a way to repair damaged nerve fibers in the CNS of people with progressive MS.

“We are excited about our findings as they hold promise for early diagnosis, targeted disease prevention and personalized therapeutic approaches for MS,” Karimi concluded.

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