Featured Research

from universities, journals, and other organizations

Deactivating Protein May Protect Nerve Fibers In Multiple Sclerosis

Date:
April 25, 2007
Source:
Oregon Health & Science University
Summary:
Neuroscientists are eyeing a protein as a potential therapeutic target for multiple sclerosis because de-activating it protects nerve fibers from damage. Researchers have shown that genetically inactivating a protein called cyclophilin D can protect nerve fibers in a mouse model of multiple sclerosis. Cyclophin D is a key regulator of molecular processes in the nerve cell's powerhouse, the mitochondrion, and can participate in nerve fiber death.

Oregon Health & Science University neuroscientists are eyeing a protein as a potential therapeutic target for multiple sclerosis because de-activating it protects nerve fibers from damage.

Related Articles


OHSU researchers, working with colleagues at the Portland Veterans Affairs Medical Center and the University of Padova in Italy, have shown that genetically inactivating a protein called cyclophilin D can protect nerve fibers in a mouse model of multiple sclerosis. Cyclophin D is a key regulator of molecular processes in the nerve cell's powerhouse, the mitochondrion, and can participate in nerve fiber death. Inactivating cyclophilin D strengthens the mitochondrion, helping to protect nerve fibers from injury. The findings are published in Proceedings of the National Academy of Sciences.

"We're extremely excited," said Michael Forte, Ph.D., senior scientist at the Vollum Institute at OHSU and the study's lead author. "While we can't genetically inactivate cyclophilin D in people, there are drugs out there that can block the protein. Our research predicts that drugs that block cyclophilin D should protect nerve fibers from damage in MS."

Such a drug would be the first therapy specifically for secondary-progressive MS, one of the more debilitating forms of MS involving an initial period of relapsing and remitting, followed by a steady worsening of symptoms. It affects half of the estimated 2 million people with MS.

The only available therapies for MS are anti-inflammatory drugs, which reduce the inflammation believed to spur certain T-cells in the body to attack myelin, the fatty sheath insulating nerve fibers in the brain and spinal cord. The fibers can't conduct impulses, leading to paralysis, memory loss, dizziness, fatigue, pain and imbalance. Over time, the nerve fibers themselves degenerate, leading to permanent functional deficits.

"All MS drugs available right now are anti-inflammatory," said study co-author Dennis Bourdette, M.D., professor and chairman of neurology in the OHSU School of Medicine, and director of the OHSU MS Center of Oregon. "What is desperately needed is a therapeutic that protects the nerve fibers from degeneration."

In recent years, scientists have increasingly viewed MS as a neurodegenerative disorder rather than simply an inflammatory one. Loss of nerve cells, injury to nerve fibers and atrophy within the central nervous system occur progressively from the start of the disease, eventually leading to permanent disability, especially in patients who've had MS for many years.

"What puts people in wheelchairs from MS is not an inflammatory attack on myelin of the central nervous system. It's the severing of the axons (nerve fibers), which is a permanent thing," Forte said.

Inflammation triggers a chain of molecular events that leads to progressive nerve fiber deterioration in MS, including the development of free radicals such as reactive oxygen and nitrogen that slow the cell's energy generation capability. It also throws off mitochondrial function by causing calcium to build up in the cell, reducing levels of ATP that serves as the cell's fuel source.

But scientists believe that cyclophilin D is responsible for causing the unregulated opening of a pore in the mitochondrion's membrane that allows the calcium overload. The OHSU team showed that mice lacking cyclophilin D still developed an MS-like disease, but unlike their counterparts possessing the protein, the mutant mice partially recovered. Scientists found their nerve fibers remained intact, and they resisted the free radicals and calcium overload.

"What we've done is make it so the mitochondria can tolerate higher loads of calcium before they die," Forte said. "The mutant mice are protected from axonal damage associated with this MS-like disease in mice."

The scientists are now testing drugs that could be used to shut down the cyclophilin D protein and the mitochondrion pore it activates. "If you basically inhibited that protein with a drug, you would see the same axonal preservation that you saw in the mutant mouse," Forte said.

One class of compounds Forte and Bourdette are particularly interested in is non-immunosuppressive derivative of cyclosporin A (CsA). Some nonimmunsuppressive derivatives of cyclosporin A are in human trials for other conditions. Because these drugs are already being tested in humans, they could be rapidly tested in MS. Bourdette believes that a cyclophilin D antagonist could potentially become available as a treatment for MS within five years.

"We don't have to invent the drugs to target this protein. They already exist," Bourdette said.

Such a therapy can't come soon enough for 36-year-old West Linn, Ore. resident Laura Wieden, who has suffered since 1995 from relapsing-remitting MS that's caused weakness in both legs and forced her to ride a Segway personal transportation device or a wheelchair. "For me, it's fabulous," she said. "If you can prevent MS, that's great, but what about the millions of people who have it? They need something that keeps the cells from dying. This just holds so much promise."

Wieden's father, Dan Wieden, co-founder of Portland-based Wieden + Kennedy advertising agency, set up a fund in his daughter's name -- the Laura Fund for Innovation in Multiple Sclerosis Research -- to support MS research that pushes traditional boundaries to discovery. The discovery by Forte, Bourdette and their team, which was funded in part by the foundation, fits the bill, he said.

"It goes to prove that sometimes the big breakthroughs do not come from the more traditional lines of inquiry," he said. "What I appreciate about our relationship with OHSU is that there seems to be a sense of urgency about these projects. And it's been beneficial for us to develop a more personal relationship with the researchers. That way it becomes not just an academic exercise, but a very passionate inquiry on their part."

Other study funders were the National Institutes of Health, the Department of Veterans Affairs and the Nancy Davis Center Without Walls.


Story Source:

The above story is based on materials provided by Oregon Health & Science University. Note: Materials may be edited for content and length.


Cite This Page:

Oregon Health & Science University. "Deactivating Protein May Protect Nerve Fibers In Multiple Sclerosis." ScienceDaily. ScienceDaily, 25 April 2007. <www.sciencedaily.com/releases/2007/04/070423185325.htm>.
Oregon Health & Science University. (2007, April 25). Deactivating Protein May Protect Nerve Fibers In Multiple Sclerosis. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2007/04/070423185325.htm
Oregon Health & Science University. "Deactivating Protein May Protect Nerve Fibers In Multiple Sclerosis." ScienceDaily. www.sciencedaily.com/releases/2007/04/070423185325.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Reuters - Light News Video Online (Dec. 19, 2014) Millions of monarch butterflies begin to descend onto Mexico as part of their annual migration south. Rough Cut (no reporter narration) Video provided by Reuters
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com
Birds Might Be Better Meteorologists Than Us

Birds Might Be Better Meteorologists Than Us

Newsy (Dec. 19, 2014) A new study suggests a certain type of bird was able to sense a tornado outbreak that moved through the U.S. a day before it hit. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins