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Columbia researchers identify drug as therapeutic candidate for spinal muscular atrophy

30.11.2004


Scientists develop data analysis tool, screen more than 47,000 compounds



Using a newly developed technology, a team of Columbia University researchers has uncovered that indoprofen, a nonsteroidal anti-inflammatory drug, may increase the production of a protein lacking in patients with spinal muscular atrophy (SMA), a fatal pediatric genetic disease.

It is the scientists’ hope that the discovery will lead to additional developments and even a treatment for SMA, a neurodegenerative disease that is the leading genetic killer of children younger than 2 in the United States and Western Europe. SMA has an incidence of 1 in 6,000 live births. Currently, no treatment exists. "Indoprofen is now both a chemical tool that researchers can use to study this disease and also a therapeutic candidate for these children," said Brent R. Stockwell, Columbia assistant professor in biological sciences and chemistry. This latest research was conducted at Stockwell’s lab, and is published in the November issue of the journal Chemistry & Biology in two separate articles: "Indoprofen Upregulates the Survival Motor Neuron Protein through a Cyclooxygenase-Independent Mechanism" and "A Flexible Data Analysis Tool for Chemical Genetic Screens."


Mitchell R. Lunn, Columbia senior research staff assistant and lead researcher on the study on indoprofen, which is structurally similar to ibuprofen, said that the next steps would be experiments to understand its mechanism of action, to deliver the drug to the spinal cord, and toxicity testing of related drug molecules. A clinical trial for its effectiveness in treating SMA could follow. It should be noted that the researchers found that ibuprofen and other nonsteroidal anti-inflammatory drugs had no effect on increasing the production of the protein lacking in individuals with SMA.

However, researchers uncovered the potential for indoprofen to increase the amount of Survival Motor Neuron (SMN) protein, the specific protein deficient in SMA patients. The results come from testing more than 47,000 compounds using a high-throughput chemical genetics approach. The data were studied with a robust analysis tool developed in the Stockwell Lab. This new software technology, known as Small Laboratory Information Management System (SLIMS), is freely available for academic use at http://slims.sourceforge.net.

"Our software package SLIMS enables researchers to analyze rapidly the mountains of data that result from chemical genetic screens," Stockwell said. For example, SLIMS is capable of organizing and "normalizing" raw data, meaning that it can "correct" for laboratory conditions such as humidity and temperature, which vary daily during the course of a high-throughput screening experiment. Additionally, SLIMS automatically identifies and corrects the systematic errors that are common with the robotic technologies used in screening.

Alissa Kaplan Michaels | EurekAlert!
Further information:
http://www.columbia.edu

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