Featured Research

from universities, journals, and other organizations

Motor Neuron Disease And Toxic Substances: Possible Link?

Date:
March 21, 2008
Source:
University of Michigan Health System
Summary:
Scientists have found that people with a form of inherited motor neuron disease have abnormalities in the same gene that appears to be affected in people who suffer nerve damage after exposure to harmful amounts of organophosphates. The results raise the possibility that healthy people may have gene variants that make them vulnerable to nerve damage if exposed to the chemicals, which include common insecticides and have been linked to Gulf War illness.

Motor neuron disease is a rare, devastating illness in which nerve cells that carry brain signals to muscles gradually deteriorate. One form of it, Lou Gehrig’s disease or ALS (amyotrophic lateral sclerosis), is familiar to the public in the lives of scientist Stephen Hawking and Morrie Schwartz, about whom Mitch Albom’s “Tuesdays with Morrie” was written.

Related Articles


For most MND patients, the cause is unknown. Figuring out why these people develop the disease, which causes muscles to weaken, atrophy and cease to function, is an important step in developing therapies to treat or prevent motor neuron disease.

Now a team of University of Michigan scientists has gotten a step closer:

  • They have discovered mutations in one key gene (neuropathy target esterase, or NTE) that cause a previously unknown type of inherited motor neuron disease.
  • The discovery paves the way for better diagnosis and research on treatments.
  • Most intriguing, the scientists found the mutations caused changes in a protein already known to be involved when people develop neurologic disorders as a result of exposure to toxic organophosphates—chemicals commonly used in solvents and insecticides and also as “nerve gas” agents. This discovery points to a new lead in the search to understand MND.

“We speculate there may be gene-environment interactions that cause some forms of motor neuron disease,” says John K. Fink, M.D., professor of neurology at the U-M Medical School and senior author of the new study, which appears in the March issue of the American Journal of Human Genetics. He also is a researcher at the VA Ann Arbor Healthcare System.

“Our findings support the possibility that toxic organophosphates contribute to motor neuron disease in genetically vulnerable people,” says Fink. He believes the results suggest that altered activity of the gene found in patients in the study may also contribute to other motor neuron disorders, possibly including ALS. Motor neuron disease affects five per 100,000 people.

The findings are an exciting first step in uncovering a possible link between the environment and motor neuron disease, says Shirley Rainier, a research assistant professor at the U-M Department of Neurology and the first author of the study. “Why does one person in a family get it, and another doesn’t?”

Piecing together a puzzle

In the 1930s, an estimated 50,000 people in the U.S. became lame or otherwise neurologically affected by neurotoxic organophosphates when they drank a contaminated batch of “ginger jake,” an alcohol-containing potion that was legal during Prohibition.

Ginger jake suppliers substituted a lubricating oil for the oil usually used, castor bean oil, when castor bean prices went up. A 2003 article in the New Yorker detailed the sad results, which led bands like the Mississippi Sheiks to write songs about the “ginger jake blues.”

More recently, there have been incidents in Fiji, India and Africa when accidental consumption of oils containing neurotoxic organophosphates (instead of cooking oil) caused death or nerve damage for tens of thousands of people. Although scientists don’t yet know the exact manner in which toxic organophosphate exposure leads to progressive and permanent nerve damage, they have learned that this process involves disturbance of an enzyme, NTE, contained within nerves.

Fink examined members of two families who had progressive weakness and spasticity (tightness) in their legs, as well as muscle atrophy in their hands, shins and feet. James Albers, M.D., Ph.D., a U-M professor of neurology and an expert in neuromuscular disorders, studied nerve and motor function. Rainier performed genetic studies and determined that the gene for the condition was on a region of chromosome 19.

Mark Leppert, Ph.D., co-chair of human genetics at the University of Utah, and his team performed genetic analysis that confirmed this location and excluded other areas in the genome. Among the many genes in this region of chromosome 19, one gene stood out as particularly likely: the gene that encodes for NTE. Because of its known role in organophosphate-induced neurological disease, the NTE gene was considered an important candidate gene and was studied immediately.

Analysis showed that the affected people in each family had NTE gene mutations. These mutations altered a critical part of the NTE protein called the esterase domain. Fink has named the inherited condition “NTE motor neuron disease.” It begins in childhood and progresses slowly, with symptoms of weakness and spasticity in the legs and muscle atrophy in the hands and lower legs.

Next, Fink and his team want to learn if mutations in the NTE gene happen in other types of motor neuron disease such as ALS, and if the mutations make a person more vulnerable to neurological damage from organophosphate exposure. Fink’s lab is currently using fruit flies as a model to study the NTE mutations, with the goal of finding treatments for people with motor neuron disease.

Other authors include Melanie Bui, Erin Mark, Donald Thomas, Debra Tokarz, Lei Ming, Colin Delaney, and James W. Albers, M.D., Ph.D., of the U-M Department of Neurology; Rudy J. Richardson, D.Sc, associate professor of neurology at U-M Medical School and Dow Professor of Toxicology in Environmental Health Sciences at the U-M School of Public Health; and Nori Matsunami, Jeff Stevens, Hilary Coon and Mark Leppert, Ph.D. of the University of Utah.

A patent application for the use of the NTE gene and protein sequence for diagnosis and treatment is pending. The University of Michigan through its Office of Technology Transfer is actively seeking a licensing partner to help bring the technology to market.

Journal reference: American Journal of Human Genetics, Volume 82, Issue 3, 780-785, 3 March 2008

Funds for this research came from the National Institutes of Health, the Veterans Affairs Merit Review, the U-M Institute of Gerontology, the Spastic Paraplegia Foundation and the National Organization for Rare Disorders.


Story Source:

The above story is based on materials provided by University of Michigan Health System. Note: Materials may be edited for content and length.


Cite This Page:

University of Michigan Health System. "Motor Neuron Disease And Toxic Substances: Possible Link?." ScienceDaily. ScienceDaily, 21 March 2008. <www.sciencedaily.com/releases/2008/03/080320163109.htm>.
University of Michigan Health System. (2008, March 21). Motor Neuron Disease And Toxic Substances: Possible Link?. ScienceDaily. Retrieved December 18, 2014 from www.sciencedaily.com/releases/2008/03/080320163109.htm
University of Michigan Health System. "Motor Neuron Disease And Toxic Substances: Possible Link?." ScienceDaily. www.sciencedaily.com/releases/2008/03/080320163109.htm (accessed December 18, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, December 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Kids Die While Under Protective Services

Kids Die While Under Protective Services

AP (Dec. 18, 2014) As part of a six-month investigation of child maltreatment deaths, the AP found that hundreds of deaths from horrific abuse and neglect could have been prevented. AP's Haven Daley reports. (Dec. 18) Video provided by AP
Powered by NewsLook.com
UN: Up to One Million Facing Hunger in Ebola-Hit Countries

UN: Up to One Million Facing Hunger in Ebola-Hit Countries

AFP (Dec. 17, 2014) Border closures, quarantines and crop losses in West African nations battling the Ebola virus could lead to as many as one million people going hungry, UN food agencies said on Wednesday. Duration: 00:52 Video provided by AFP
Powered by NewsLook.com
When You Lose Weight, This Is Where The Fat Goes

When You Lose Weight, This Is Where The Fat Goes

Newsy (Dec. 17, 2014) Can fat disappear into thin air? New research finds that during weight loss, over 80 percent of a person's fat molecules escape through the lungs. Video provided by Newsy
Powered by NewsLook.com
Why Your Boss Should Let You Sleep In

Why Your Boss Should Let You Sleep In

Newsy (Dec. 17, 2014) According to research out of the University of Pennsylvania, waking up for work is the biggest factor that causes Americans to lose sleep. 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


Health & Medicine

Mind & Brain

Living & Well

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