|A colony of iPS cells, courtesy of Kathrin Plath at the University of California, Los Angeles.|
There’s a lot of talk these days about studying diseases and finding new drugs using stem cells. The idea is so compelling that CIRM has entered into a partnership with the NIH to create the kinds of cell banks that would be needed to carry out this work, specifically in Parkinson’s disease, Huntington’s disease, and ALS (Lou Gehrig’s disease).
Now, results of that work are starting to be published. The most recent paper in the July 4 issue of Science Translational Medicine and shows that of the many different mutations that can lead to Parkinson’s disease some also cause neurons to be more susceptible to certain kinds of toxins. Drugs that normally protect cells from damage effectively protected the neurons created from people who had one Parkinson’s disease mutation, but not another.
What this means is that people who get Parkinson’s disease for different genetic reasons might also respond differently to drugs. In a press release, the NIH suggests that these findings could be used to make sure people get the right drugs for their form of the disease.
The idea behind this and other studies hinges on the fact that there is no way to directly study the neurons of people with neurological diseases like Parkinson’s, Alzheimer’s or Huntington’s disease and many others. So instead, scientists take skin cells from people with the disease. Those skin cells contain the same mutations that led to the disease in the people’s neurons. They then convert those skin cells into embryonic-like iPS cells, and mature the iPS cells into neurons. Those neurons mimic the neurons of people who have the disease, and in many cases behave very differently in a lab dish compared to neurons generated from the skin of healthy people.
With these diseased neurons to study, scientists are for the first time starting to understand the origin of many previously mysterious neurological diseases. They can also start testing drugs to see which ones eliminate symptoms of the disease in the lab.
This study came out of a collaboration between the NIH’s National Institute of Neurological Disorders and Stroke and several other funding agencies including CIRM. A similar consortium of funders sponsored related work in Huntington’s disease that we wrote about last week.
CIRM considers this work so important that we’ll soon be releasing a new round of funding to support creating and banking iPS cells from people with a wide variety of diseases beyond the three in our NIH agreement. This CIRM press release describes that program. You can also read about our banking initiative in our annual report.
Cooper O, Seo H, Andrabi S, Guardia-Laguarta C, Graziotto J, Sundberg M, McLean JR, Carrillo-Reid L, Xie Z, Osborn T, Hargus G, Deleidi M, Lawson T, Bogetofte H, Perez-Torres E, Clark L, Moskowitz C, Mazzulli J, Chen L, Volpicelli-Daley L, Romero N, Jiang H, Uitti RJ, Huang Z, Opala G, Scarffe LA, Dawson VL, Klein C, Feng J, Ross OA, Trojanowski JQ, Lee VM, Marder K, Surmeier DJ, Wszolek ZK, Przedborski S, Krainc D, Dawson TM, & Isacson O (2012). Pharmacological Rescue of Mitochondrial Deficits in iPSC-Derived Neural Cells from Patients with Familial Parkinson’s Disease. Science translational medicine, 4 (141) PMID: 22764206