Gene that causes sometimes lateral sclerosis als family discovered (science daily)

PharmaLive.com (9 December 2010) - using a new method of sequencing of the genes, a team of researchers led by scientists at Johns Hopkins and the National Institutes of Health has discovered a gene that seems to cause some cases unrelated amyotrophic lateral sclerosis (ALS). The findings could lead to new ways to treat the most common form of this fatal neurodegenerative disease that kills the vast majority of Americans close to 6,000 diagnosed with ALS each year.

Researchers don't know exactly what causes ALS, which destroys the motor neurons that control the movement of the muscles of the body, including those that control breathing. However, studies of familial disease, which affects the 5-10% of people with Alzheimer's, might shed some light on why motor neurons die in all types of ALS, says Bryan j. Traynor, M.D., Assistant Professor in the Department of Neurology at the Johns Hopkins University School of Medicine and Chief of the research group study neuromuscular diseases at the National Institutes of Health.

"If you look at the spectrum of diseases caused by the dysfunctional genes, our understanding of almost all from a familial disease," explains Traynor. By finding the genes associated with these diseases, he said, researchers can insert causative genes in animals, creation of models that can help them to decipher what's happening to cause pathologies and find ways to stop them.

Scientists were already aware of a handful of genes which seems to cause some family als cases. The new study, published in the journal Neuron, December 9 Traynor and his colleagues used a new technique called exome sequencing to seek more. This new technique differs from most common gene sequencing type because it focuses only on 1-2% of that code for proteins and ignores other non-codage DNA genome. Exome sequencing of thousands of genes at the same time, rather than sequencing step by step the more traditional method, exome sequencing much faster sequences.

The Traynor team worked with two affected members of an Italian family discovered by colleague Adriano Chiò, M.D., of the University of Turin, SLA expert who maintains a register of all cases of the disease by Jessica Mandrioli, MD, University of Modena and Italy North. Using sequencing exome on these two ALS patients and 200 people without the disease, scientists examined the differences in gene ALS patients had in common that differ from the other samples. Their research led to a gene called CRS, abbreviation of valosin containing protein.

When researchers have sought other cases in which this gene was transferred in additional 210 ALS patients, they found four different mutations affecting the VCP in five persons. None of these mutations were found in the genomes of hundreds of healthy controls, suggesting that the secure channel is indeed the cause of some of the ALS cases.

Although scientists don't always know exactly how to posted SC could lead to the SLA, they know that this gene plays a role in a process called ubiquination, the tags of proteins for degradation. A glitch in the process could result in too or too little of certain proteins are present in engines, neurons leading to death. Finally, said scientific Traynor may be able to develop drugs that could transform this pathological process a healthy patients with ALS, save the motor neurons that otherwise dead.

This work was funded in part by the NIH, National Institute on aging and the national Institute on neurological diseases and stroke intramural programming. Work was also funded by the Packard Center for research at Johns Hopkins University, the Fondazione Vialli e Mauro ALS research Onlus, Federazione Italiana Calcio unfinished, Ministero della Salute, the Muscular Dystrophy Association and the Woodruff Health Sciences Center of Emory SLA.

Jeffrey Rothstein, M.D., of Johns Hopkins University, participated in this study.

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Source of the story:

The story above is reproduced (with drafting adaptations by staff at PharmaLive.com) materials provided by Johns Hopkins Medical Institutions.

Reference of the review:

Janel o. Johnson et al. Exome sequencing shows that CRS mutation as a cause of ALS family. Neuron, vol. 68, no. 5, 857-864, 9 December 2010 DOI: 10.1016/j.neuron.2010.11.036

Note: If no author is given, the source is cited for this.