Ataxia patients and family members learn about stem cell progress

I was scheduled to give a talk to the Northern California Ataxia Support Group Saturday, just 15 minutes before the Fortyniners were about to begin their first playoff game in years. A colleague picked me up at the local BART train station and we drove up to a mostly empty parking lot at the church where the meeting was supposed to take place. We wandered through the empty upper halls and as we approached a stairwell started to hear voices. Turned out the church has a second parking lot on the back side that opens to a lower level—key for the 30 some individuals gathered that day, many mobility challenged, who were gathered around two long tables.

For them the chance to get together to share information about their poorly understood mix of diseases and to hear about the promise of stem cells was more important than the football game some commentators were calling historic. Ataxia refers to an assortment of conditions, some inherited and some sporadic that all involve the nervous system with primary symptoms related to gait and mobility. They also have the commonality of being relatively poorly understood and ineffectively treated with current standards of care.

I did not come prepared to offer them news that we were close to clinical trials using stem cells to treat their diseases. We are not. But I was armed with news of two grants CIRM has funded that have already improved our understanding of a couple of ataxias and perhaps opened up the opportunity to find more effective traditional small molecule drugs. CIRM has funded two teams, one at UCLA and one at Scripps, that are both using cell samples form ataxia patients to create reprogrammed stem cells, called induced Pluripotent Stem Cells (iPSC), to create “disease-in-a-dish” models.

One team has already published a journal article on its model of Friedreich’s Ataxia (Cell Stem Cell, November 5, 2010), which offered a better explanation of the mutation involved in the disease, offering a point of departure for addressing the mutation. The other team is working on a form of ataxia that goes by the acronym A-T that is a particularly debilitating form that strikes children. It was known to be caused by a type of mutation called a “nonsense” coding error in the DNA. The team had previously developed several compounds that would allow the patient’s cellular machinery to read through the nonsense coding and go ahead and produce the protein that is missing in these kids. But there is no animal model of these diseases so there was no way to do the pre-clinical testing required to put the compounds in clinical trials in humans. Now they will have a model, cells from patients in a dish. So, there is hope one of those compounds can be shown to be worthy of a clinical trial.

This meeting was one of many that CIRM holds with patient advocacy groups in California as a way of ensuring that those groups who have the most at stake know about progress being made in developing therapies for the diseases that matter to them. These groups played a critical role in the creation of CIRM, and continue to have a loud voice in pushing CIRM to maintain our focus on new therapies. CIRM also keeps advocacy at the core of its mission through input from the 10 patient advocates who serve on our board. Our board member Jeff Sheehy wrote a blog entry on the importance of patient advocates in steering funding agencies like CIRM.

My audience and I had a good conversation about the long-term hope stem cell research provides. They seemed excited by this hope, but also exhibited a gentle patience, probably a brand of patience that can only be instilled by years of living with an intractable disease.

I got home in time to see the final few incredible minutes of the nail-biting football game and to hear our neighborhood explode with fire crackers and honking horns, but I did not regret one bit missing those first three quarters of play. That game ending was just the icing on a very satisfying cake.

DG

Ku S, Soragni E, Campau E, Thomas EA, Altun G, Laurent LC, Loring JF, Napierala M, & Gottesfeld JM (2010). Friedreich’s ataxia induced pluripotent stem cells model intergenerational GAA⋅TTC triplet repeat instability. Cell stem cell, 7 (5), 631-7 PMID: 21040903