The pancreas provides a potential drug candidate for brain disease

August 24, 2017

(Osaka, Japan) Brain functions are maintained by the neural network. Neural network is formed by the connection between the neurite, and this connection is supported by the wrapping of myelin. Demyelination is detected in the patients of several diseases, such as multiple sclerosis, and is associated with neurological dysfunctions. A new study in The Journal of Clinical Investigation by scientists at Osaka University shows that fibroblast growth factor (FGF) 21 promotes remyelination in mice and may be a promising key molecule for treating demyelinating diseases.

In normal development, oligodendrocyte precursor cells (OPCs) differentiate into oligodendrocytes, which are required for myelination. OPCs will proliferate around the lesions of demyelination after injury and contribute to spontaneous remyelination, but the molecular mechanism of OPCs proliferation is not fully clarified. Osaka University Associate Professor Rieko Muramatsu focused on the blood leakage around demyelinating lesion. "Factors in the blood cannot reach the normal brain because central nervous system has blood-brain barrier. In demyelination diseases like multiple sclerosis, the blood-brain barrier around the lesion is disrupted," she said.

Muramatsu suspected that with the breach, factors from peripheral organs secreted into the blood could now reach the brain.

To test her hypothesis, "We disrupted the vascular barrier and myelin structures in mice by injecting Lysophosphatidylcholine (LPC). We looked for circulating factors that promote OPCs proliferation and found FGF21 as a candidate," she said.

FGF21 is secreted by the pancreas.

Mice treated with LPC showed high levels of FGF21 around demyelinated lesions leading to remyelination. This was not the case in mutant mice that could not express FGF21. Other mice that received direct administration of FGF21 to demyelinated lesions caused by LPC injection also showed increased remyelination and better recovery of neurological function.

In addition, the researchers found OPCs expressed higher levels of β-klotho, co-receptor for FGF21, following LPC injection. Without this expression, FGF21 could not promote remyelination.

"FGF21 is known to regulates metabolism, but its effects on OPC proliferation were unexpected," said Muramatsu.

The results suggest that FGF21 has therapeutic potential for demyelinating diseases. FGF21 analogs are already being used for clinical studies on diabetes, which means its development for remyelination could go faster than had it been an untested compound.

"There are many drugs that inhibit demyelination, but none that promote remyelination. FGF21 is a new candidate that deserves more testing. The most important finding is that we show the peripheral milieu promotes central nervous system remyelination."
-end-


Osaka University

Related Multiple Sclerosis Articles from Brightsurf:

New therapy improves treatment for multiple sclerosis
A new therapy that binds a cytokine to a blood protein shows potential in treating multiple sclerosis, and may even prevent it.

'Reelin' in a new treatment for multiple sclerosis
In an animal model of multiple sclerosis (MS), decreasing the amount of a protein made in the liver significantly protected against development of the disease's characteristic symptoms and promoted recovery in symptomatic animals, UTSW scientists report.

Not all multiple sclerosis-like diseases are alike
Scientists say some myelin-damaging disorders have a distinctive pathology that groups them into a unique disease entity.

New therapeutic options for multiple sclerosis in sight
Strategies for treating multiple sclerosis have so far focused primarily on T and B cells.

Diet has an impact on the multiple sclerosis disease course
The short-chain fatty acid propionic acid influences the intestine-mediated immune regulation in people with multiple sclerosis (MS).

The gut may be involved in the development of multiple sclerosis
It is incompletely understood which factors in patients with multiple sclerosis act as a trigger for the immune system to attack the brain and spinal cord.

Slowing the progression of multiple sclerosis
Over 77,000 Canadians are living with multiple sclerosis, a disease whose causes still remain unknown.

7T MRI offers new insights into multiple sclerosis
Investigators from Brigham and Women's Hospital have completed a new study using 7 Tesla (7T) MRI -- a far more powerful imaging technology -- to further examine LME in MS patients

How to improve multiple sclerosis therapy
Medications currently used to treat multiple sclerosis (MS) can merely reduce relapses during the initial relapsing-remitting phase.

Vaccinations not a risk factor for multiple sclerosis
Data from over 12,000 multiple sclerosis (MS) patients formed the basis of a study by the Technical University of Munich (TUM) which investigated the population's vaccination behavior in relation to MS.

Read More: Multiple Sclerosis News and Multiple Sclerosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.