Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Pain reliever may help treat life-threatening childhood disease


A drug withdrawn from pharmacy shelves over 20 years ago may point the way to a new treatment for spinal muscular atrophy, or SMA, a muscle-wasting and often life-threatening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

More articles from Life Sciences:

nachricht Biologists unravel another mystery of what makes DNA go 'loopy'
16.03.2018 | Emory Health Sciences

nachricht Scientists map the portal to the cell's nucleus
16.03.2018 | Rockefeller University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Locomotion control with photopigments

Researchers from Göttingen University discover additional function of opsins

Animal photoreceptors capture light with photopigments. Researchers from the University of Göttingen have now discovered that these photopigments fulfill an...

Im Focus: Surveying the Arctic: Tracking down carbon particles

Researchers embark on aerial campaign over Northeast Greenland

On 15 March, the AWI research aeroplane Polar 5 will depart for Greenland. Concentrating on the furthest northeast region of the island, an international team...

Im Focus: Unique Insights into the Antarctic Ice Shelf System

Data collected on ocean-ice interactions in the little-researched regions of the far south

The world’s second-largest ice shelf was the destination for a Polarstern expedition that ended in Punta Arenas, Chile on 14th March 2018. Oceanographers from...

Im Focus: ILA 2018: Laser alternative to hexavalent chromium coating

At the 2018 ILA Berlin Air Show from April 25–29, the Fraunhofer Institute for Laser Technology ILT is showcasing extreme high-speed Laser Material Deposition (EHLA): A video documents how for metal components that are highly loaded, EHLA has already proved itself as an alternative to hard chrome plating, which is now allowed only under special conditions.

When the EU restricted the use of hexavalent chromium compounds to special applications requiring authorization, the move prompted a rethink in the surface...

Im Focus: Radar for navigation support from autonomous flying drones

At the ILA Berlin, hall 4, booth 202, Fraunhofer FHR will present two radar sensors for navigation support of drones. The sensors are valuable components in the implementation of autonomous flying drones: they function as obstacle detectors to prevent collisions. Radar sensors also operate reliably in restricted visibility, e.g. in foggy or dusty conditions. Due to their ability to measure distances with high precision, the radar sensors can also be used as altimeters when other sources of information such as barometers or GPS are not available or cannot operate optimally.

Drones play an increasingly important role in the area of logistics and services. Well-known logistic companies place great hope in these compact, aerial...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

International Virtual Reality Conference “IEEE VR 2018” comes to Reutlingen, Germany

08.03.2018 | Event News

Latest News

Wandering greenhouse gas

16.03.2018 | Earth Sciences

'Frequency combs' ID chemicals within the mid-infrared spectral region

16.03.2018 | Physics and Astronomy

Biologists unravel another mystery of what makes DNA go 'loopy'

16.03.2018 | Life Sciences

Science & Research
Overview of more VideoLinks >>>