Tuesday, May 14, 2013

Getting rid of a protein that promotes longer lifespan slows MS in mice

Neuron showing the protective sheath that is lost in people with multiple sclerosis
Our grantees at Stanford University have found a protein with an intriguing role in the development of multiple sclerosis. The work is still in mice, but points to a new pathway for developing drugs for the disease.

People with MS slowly lose the protective covering that surrounds their neurons. Over time, the damage leads to paralysis. There is currently no cure and no therapy that does more than just slow how quickly the disease progresses.

The group, led by Anne Brunet, was studying a protein called SIRT1, which has been dubbed the "skinny gene" because of it's role in helping animals burn fat. In animals, having high levels of SIRT1 seems to extend lifespan. In fact, if you search the web on SIRT1 or "skinny gene" you will find scores of companies offering to sell products or diet plans intended to help you mimic those animal studies.

So, SIRT1 seems to be something you'd want to have around. But Brunet's group found the opposite, at least when it came to MS. They were using a special group of mice that contained SIRT1 genes that the scientists could turn on and off. They then induced a form of MS in these mice and turned off the SIRT1 gene. Mice without SIRT1 were protected from the paralysis that struck their fellow mice with normal levels of SIRT1.

Stanford quoted Brunet in a press release about the work (myelin is that protective covering lost in MS):
“We are excited by the potential implications our study has on demyelinating diseases and injuries. It’s intriguing because activating SIRT1 is typically considered to be beneficial for metabolism and health, but in this case, inactivating SIRT1 can provide protection against a demyelinating injury.”
They went on to find other genes that are activated in mice lacking SIRT1. These genes appear to work by promoting neural stem cells to turn into the type of cells that form that protective sheath.

Brunet says finding drugs that manipulate these genes could be one step toward finding a therapy for the disease. The work was published online May 5 in Nature Cell Biology.

There's more information about CIRM's funding for multiple sclerosis research on our website, including a list of awards and descriptions of therapy development projects.

A.A.

ResearchBlogging.orgRafalski VA, Ho PP, Brett JO, Ucar D, Dugas JC, Pollina EA, Chow LM, Ibrahim A, Baker SJ, Barres BA, Steinman L, & Brunet A (2013). Expansion of oligodendrocyte progenitor cells following SIRT1 inactivation in the adult brain. Nature cell biology PMID: 23644469

2 comments:

  1. The best paper of the decade!

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  2. Experimental use of stem-cell therapy approved for Italy
    Rome, May 15 - Legislation permitting the experimental use of stem cells in medical therapies was approved Wednesday by Italian politicians on the social affairs committee. An amendment to existing law received unanimous approval for the testing of stem-cell therapy under controlled conditions approved by the Ministry of Health. As well, three million euro from the national health fund will be allocated for the testing, which is to begin July 1 and extend for 18 months. The committee has officially approved what is already the practice in at least one Italian hospital, despite court rulings against the procedure. A toddler at the Brescia hospital in northern Italy has been undergoing stem-cell treatment which the government grudgingly approved of in March. At the time, the health minister said it would be risky to the child's health to stop treatments that were underway. Treatments for local toddler Celeste Carrer involve stem-call transplants from her mother's bone marrow, and began 18 months ago to halt the spinal muscular atrophy causes the toddler's muscles to waste away. Celeste was reportedly able to move her neck, arms, and legs following an early treatment. Stem-cell treatment, which is legal in Italy in life-threatening instances, is contentious because it sometimes involves the destruction of a human embryo. Italy banned the use of embryos in stem cell research in 2004, but in 2007 Italian researchers obtained adult stem cells which they said were as effective as those obtained from embryos. http://www.gazzettadelsud.it/news/english/46607/Experimental-use-of-stem-cell-therapy-approved-for-Italy.html

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