Featured Research

from universities, journals, and other organizations

New approaches open up in spinal muscular atrophy: Failure in nerve-fiber navigation corrected in zebrafish model

Date:
June 10, 2011
Source:
Children's Hospital Boston
Summary:
Spinal muscular atrophy (SMA) is the leading genetic cause of death in children under 2, with no treatment other than supportive care. In a new study, researchers show how loss or mutation of the SMA gene causes progressive muscle degeneration and weakness, and suggest a promising approach to treating the condition, sometimes referred to as a "Lou Gehrig's disease of babies."

Spinal muscular atrophy (SMA) is the leading genetic cause of death in children under 2, with no treatment other than supportive care. In the Proceedings of the National Academy of Sciences, researchers at Children's Hospital Boston show how loss or mutation of the SMA gene causes progressive muscle degeneration and weakness, and suggest a promising approach to treating the condition, sometimes referred to as a "Lou Gehrig's disease of babies."

Spinal muscular atrophy, or SMA, affects one in every 1 in 6,000-10,000 infants, but an estimated 1 in 35-40 people are carriers, according to the SMA Foundation. Infants with SMA are born with low muscle tone, and in many cases are too weak to breathe and swallow on their own; they usually die from respiratory failure.

The new findings reveal that loss of the SMA gene -- and resulting depletion of a protein called SMN -- makes nerve fibers from the spinal cord unable to navigate toward and form synapses (connections) with the muscles they're meant to control. But they also demonstrate that this problem could be reversed in a zebrafish model of the disease.

To figure out the function of the SMN protein, the researchers, led by Mustafa Sahin, MD, PhD, and Judith Steen, PhD, of Children's F.M. Kirby Neurobiology Center, began by asking what SMN interacts with. They used mass spectrometry, a technique from proteomics, to see what proteins SMN binds to.

One protein, called HuD, was a strong hit. The team also showed that SMN and HuD are found together in the nerve fibers (axons) that branch from motor neurons, and that both bind to RNAs that seem to regulate the production of another protein, neuritin (also called cpg15).

Sahin then collaborated with Christine Beattie, PhD (The Ohio State University), who had developed a zebrafish model of this disease. When the SMN protein was blocked in zebrafish embryos, the axons were clearly abnormal. "They branch in the wrong directions and don't really reach the right muscle," says Sahin. "We thought this could be due to neuritin loss and asked, 'can we put back neuritin and make the axons normal?'"

When they stimulated production of neuritin artificially -- by injecting neuritin RNA into zebrafish embryos -- the axons branched normally from the spinal cord and made normal connections to muscle.

Sahin notes that neuritin is secreted outside the neuron, meaning it probably acts on a surface receptor. That makes neuritin or similarly-acting compounds good candidates for drug therapy. The next step is to find that neuritin receptor and drugs that would stimulate it, including modified forms or fragments of neuritin itself. In upcoming experiments, Sahin's team will shift to mice and try different ways of delivering neuritin or related compounds, and then see if muscle strength and survival improve.

Current research the SMA field focuses on making more of the depleted SMN protein itself. This is relatively easy to accomplish for cells in a culture dish, but it's hard to get artificially introduced SMN to function in motor neurons within the spinal cord, Sahin says. In mouse models, increasing SMN does appear to increase muscle strength, and the mice live longer. But in human clinical trials, this approach has not yet produced positive results.

The discovery of neuritin suggests an alternative and possibly more direct way of trying to do the same thing; perhaps this would widen the window of opportunity for treatment. "SMA is such a devastating disease currently," says Sahin. "There is no cure. So far, we can only manage the symptoms and prevent complications.."

Bikem Akten, PhD, of Children's F.M. Kirby Neurobiology Center was first author on the paper. The study was performed in collaboration with Christine Beattie, PhD, (The Ohio State University) and Jeffery Twiss, MD, PhD (Drexel University). The study was funded by the National Institutes of Health, the Slaney Family Fund, the SMA Foundation, the American Academy of Neurology Foundation, the Children's Hospital Boston Translational Research Program, the Children's Hospital Boston Mental Retardation and Developmental Disabilities Research Center, the William Randolph Hearst Foundation and the Harvard Neurodiscovery Center.


Story Source:

The above story is based on materials provided by Children's Hospital Boston. Note: Materials may be edited for content and length.


Journal Reference:

  1. Bikem Akten, Min Jeong Kye, Le T. Hao, Mary H. Wertz, Sasha Singh, Duyu Nie, Jia Huang, Tanuja T. Merianda, Jeffery L. Twiss, Christine E. Beattie, Judith A. J. Steen, Mustafa Sahin. Interaction of survival of motor neuron (SMN) and HuD proteins with mRNA cpg15 rescues motor neuron axonal deficits. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1104928108

Cite This Page:

Children's Hospital Boston. "New approaches open up in spinal muscular atrophy: Failure in nerve-fiber navigation corrected in zebrafish model." ScienceDaily. ScienceDaily, 10 June 2011. <www.sciencedaily.com/releases/2011/06/110606152200.htm>.
Children's Hospital Boston. (2011, June 10). New approaches open up in spinal muscular atrophy: Failure in nerve-fiber navigation corrected in zebrafish model. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2011/06/110606152200.htm
Children's Hospital Boston. "New approaches open up in spinal muscular atrophy: Failure in nerve-fiber navigation corrected in zebrafish model." ScienceDaily. www.sciencedaily.com/releases/2011/06/110606152200.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 Video provided by AFP
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:
from the past week

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