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New Study Finds Biological Pathways for ALS Progression

by VR Sreeraman on Aug 5 2007 4:11 PM

A new study has discovered biological pathways for the progression of sporadic amyotrophic lateral sclerosis (ALS). ALS is a progressive, fatal, neuro-degenerative disease caused by the degeneration of motor neurons, in the central nervous system.

ALS is sometimes also called Lou Gehrig's disease.

In the study, blood samples from more than 220 ALS patients at the Methodist Neurological Institute were used in research that revealed significant changes in or around 10 specific genes in sporadic ALS.

“This discovery has helped identify new biological pathways for the progression of ALS in individuals with this debilitating disease,” said Dr. Stanley Appel, chair of the department of neurology at The Methodist Hospital and co-founder of the Methodist Neurological Institute in Houston.

“ALS is most likely caused by a combination of environmental and genetic components. This type of study provides us with a better understanding of the genetic contribution,” he added.

Sporadic (non-inherited) ALS affects 90 percent of the ALS population. This population is representative of the patients at the MDA/ALS Clinic and Research Center at the Methodist Neurological Institute, the first and one of the largest multi-disciplinary ALS clinics in the nation.

“Our incredible, courageous patients were able to personally contribute to our quest to find a cure for ALS by providing their own blood toward our joint mission,” said Appel, co-author of the paper. “I hope that our work honours them with real results that can improve their lives and the lives of those who might some day be cured of ALS,” he said.

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According to the study, this gene discovery points to several genetic breakdowns that might make people more susceptible to ALS. One set of genetic loci, the area in and around the gene, involves cell scaffolding that helps maintain structure of certain key cells. Another involves stickiness at the junction of nerves and muscles. And a last indication involves inflammation that can lead to ALS characteristics.

Using state-of-the-art micro-array technology to quickly analyze thousands of genes in a full genome (complete set of genes), the investigators scanned for differences in the blood samples from 1,200 people with and 2,000 people without sporadic ALS.

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Method Researchers performed a genome-wide association analysis using 766,955 single-nucleotide polymorphisms (SNPs) found in 386 patients with sporadic ALS and 542 neurologically normal controls (the discovery series). Associations were confirmed in two independent replication populations: replication series 1, with 766 case patients and 750 neurologically normal controls, and replication series 2, with 135 case patients and 275 controls.

Source-ANI
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