Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Pain reliever may help treat life-threatening childhood disease

30.11.2004


A drug withdrawn from pharmacy shelves over 20 years ago may point the way to a new treatment for spinal muscular atrophy, or SMA, a muscle-wasting and often life-threatening childhood disease.



A new study suggests that the drug, called indoprofen, increases the production of a protein that is key to the survival of the nerve cells affected by the disease. Indoprofen was taken off the market in the early 1980s due to reports of serious gastrointestinal reactions as well as reports that the drug caused cancer in laboratory rats. Researchers are now looking into ways to modify the drug to make it less toxic to humans, said Arthur Burghes, a study co-author and a professor of molecular and cellular biochemistry at Ohio State University.

While SMA strikes only about one in 6,000 newborn Americans each year, it is the leading genetic cause of infant and toddler death in the United States as well as Western Europe. There is no cure or standard treatment, and children with the most severe form of the disease usually die before their second birthday. Motor neurons – nerve cells that send signals from the spinal cord to muscles throughout the body – rapidly deteriorate in SMA due to reduced levels of survival motor neuron (SMN) protein. Patients with the disease lack SMN1, a gene that produces SMN protein. For reasons that aren’t clear, this protein deficiency affects only motor neurons of the spinal cord – all other cells in the body function normally.


SMA patients do have one or more copies of SMN2, a gene that produces low levels of SMN protein. But these levels aren’t high enough to stop SMA’s deleterious effects on spinal motor neurons. Laboratory experiments using indoprofen to treat human fibroblast cells resulted in a 13 percent increase in SMN protein production in the cells. "This increase is sort of like giving an additional SMN2 gene to a patient – it would give the patient about 13 to 15 percent more protein," Burghes said. "While this additional protection wouldn’t cure the disease, it could lessen the severity of symptoms."

The study appears in the current issue of the journal Chemistry and Biology. Burghes worked with a team of scientists from Columbia University, the National Institutes of Health, the University of Massachusetts Medical School and a hospital in the United Kingdom. Brent Stockwell, the study’s principal investigator, is a researcher at Columbia University.

The researchers screened 47,000 chemical compounds to find ones that would boost SMN2’s protein production capabilities. Included in this group were a number of non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. Out of all the compounds screened, indoprofen was the only drug – including the only NSAID – that showed an effect. Researchers used human fibroblasts taken from patients with Type I SMA, the most severe form of the disease. While SMA doesn’t harm fibroblasts, the cells still lack the SMN1 gene. "We can’t extract spinal neurons from humans, and the fibroblasts gave us a pretty good idea of indoprofen’s affect on human cells," Burghes said.

SMN protein production increased by 13 percent in the treated fibroblasts.

"Theoretically, children with less severe forms of SMA may get even more protection than this, since these children have more copies of the SMN2 gene than do children with the most severe form," Burghes said.

The researchers also tested indoprofen’s effects on mice pregnant with SMA offspring. "What is still unclear is at what point motor neurons most need the additional SMN protein," Burghes said. "Should we give treatment once a patient has symptoms, before the symptoms start, or even in utero? We just don’t know." Even so, indoprofen still gives researchers a good starting point for creating drugs to help treat SMA, he said. "The next step is to work on modifying the drug to make it an optimal compound for treating SMA, and to try to find other compounds that work in a similar way," Burghes said. "Chemical modification of indoprofen will hopefully help us create a better drug."

This work was funded by grants from Andrew’s Buddies, Families of SMA and the National Institutes of Health. Work in Burghes’ laboratory has also been supported by the Miracle for Madison fund at Ohio State.

Arthur Burghes | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>