One of the biggest hurdles in understanding and treating neurological diseases is figuring out what has gone awry with those cells. People aren’t generally eager to donate a chunk of their brains for research. With the advent of reprogrammed iPS cells scientists have been able to recreate the diseases in a lab dish and begin to understand the origin of those diseases.
In the past few years, CIRM grantees have taken skin cells from people with Parkinson’s disease, schizophrenia and forms of autism, reprogrammed those into embryonic-like cells, and matured them into the cells that go awry in the disease. (We blogged about Parkinson’s here, schizophrenia here, and one form of autism here.)
The latest of these studies comes from CIRM grantee Ricardo Dolmetsch at Stanford University, who has created nerve cells out of people with the rare genetic disorder called Timothy Syndrome that includes autism as a symptom. Dolmetsch came to this research for personal reasons. In a conversation with Paul Costello in Stanford’s 1:2:1 podcost, he talked about his son, who was diagnosed with autism at age 4. In that interview he told Costello how that diagnosis altered the direction of his work:
“The thing that was disconcerting is that I’m an academic and I was horrified to discover that very little was known. And so I thought I’m a neurobiologist and I don’t work on this but at least in principle I could. And so I decided to turn my lab toward studying autism.”
As a part of that new research direction, Dolmetsch got a CIRM Tools & Technologies II award to use nerve cells created from the skin of people with Timothy syndrome to attempt to find drugs that reverse the symptoms, at least in the lab dish. A Stanford press release describes their findings:
In this study, the scientists suggest that the autism in Timothy syndrome patients is caused by a gene mutation that makes calcium channels in neuron membranes defective, interfering with how those neurons communicate and develop. The flow of calcium into neurons enables them to fire, and the way that the calcium flow is regulated is a pivotal factor in how our brains function.
The researchers also found brain cells grown from individuals with Timothy syndrome resulted in fewer of the kind of cells that connect both halves of the brain, as well as an overproduction of two of the brain’s chemical messengers, dopamine and norepinephrine. Furthermore, they found they could reverse these effects by chemically blocking the faulty channels.
In the release, Dolmetsch points out that although they did fund a chemical that reverses the effects, that chemical, called roscovitine, is not currently approved for use in humans and has never been tested in children. He said:
“The reported side effects are probably due to the fact that, in addition to targeting the channel that is mutated in autism, roscovitine also inhibits kinases that are required for cell proliferation. We think that roscovitine is a good starting point, but probably has to be optimized before it would be useful for autism.”