|Stem cells at different stages of maturing into nerve cells like those affected by A-T. Image was taken in the lab of Guoping Fan at the University of California, Los Angeles.|
CIRM grantees at UCLA did just that in a rare disease called ataxia-telangiectasia (A-T). This disease appears when kids are early school age and can lead to problems moving as well as with the immune system and other organs. The disease can be quite variable, but most people die by early adulthood. (Here's more about the condition from the NIH.)
As with so many diseases, scientists can't develop a therapy if they don't really know what's going wrong in the patient's cells. There are no good ways of mimicking A-T in lab animals, and people with the disease aren't likely to donate a few brain cells for scientists to study in a dish. This leaves scientists guessing when it comes to finding a way of treating a disease they don't understand.
Enter stem cells. Scientists can now take a few skin cells from a person with A-T, turn those into embryonic-like stem cells and then push them to form the types of neurons that don't function properly. Essentially, they took the patient's skin and from that created a part of the patient's brain.
Although these cells came from skin, they have all the same DNA as in cells of the brain, including the mutation that causes A-T. Now, with their lab dish version of A-T scientists can study what's wrong with those cells. This technique is called creating a "disease-in-a-dish" and has been used by scientists to better understand Parkinson's, Huntington's and Alzheimer's diseases, schizophrenia, forms of autism and many other conditions. (We've blogged about that work here.)
The UCLA team started exposing the cells in a lab dish to a variety of drugs, and found some that appear to make those cells function more normally. The drugs in question are ones that helps the cells essentially ignore a mutation like the one that causes A-T. Its real name is a small molecule read-through (SMRT) compounds.
The good news here is that this is the first time scientists have been able to directly test drugs on cells that have A-T. However, there are a lot of steps between finding a promising drug in the lab and having a therapy available to people. These cells were essentially bathed in the compound, which is pretty different than what happens when people take a drug, and these cells also had no other organs that could be damaged by the drug. These issues are why it's such a long and often frustrating path from the lab bench to the patient's bedside.
CIRM funding: Richard Gatti (RT2-01920)
Lee, P., Martin, N., Nakamura, K., Azghadi, S., Amiri, M., Ben-David, U., Perlman, S., Gatti, R., Hu, H., & Lowry, W. (2013). SMRT compounds abrogate cellular phenotypes of ataxia telangiectasia in neural derivatives of patient-specific hiPSCs Nature Communications, 4 DOI: 10.1038/ncomms2824