State of the Foundation: a short update

The Jain Foundation has evolved from an inspired idea to a team intricately involved in driving forward the dysferlin field. Our evolution was the direct response to the lessons we learned. The Foundation now has the default ownership of the direction of the field. Although our approach to active management was initially met with resistance, this was natural given that basic research has never been managed, let alone as intensely as by us.

The researchers in the dysferlin field are seeing their productivity increase as a direct result of their collaborations with each other and the greater availably of tools. We am happy to report that only a few isolated silos remain in the dysferlin field. Now when we fund a project listing specific experiments, we are confident that the experiments will be performed and that they will yield a result be it positive or negative.

Because a large percentage of results in this inherently high risk endeavor are negative, increasing the frequency of obtaining results is the best chance of moving forward. Already, our comprehension of dysferlin deficiency and how to fight it has grown significantly. For example, the realization that a technical glitch prevented us from “seeing” that the majority of dysferlin is located in the T-tubules inside of a muscle fiber, rather than on the surface membrane, has changed our view of how the absence of dysferlin leads to disease. The limited ability of an AAV virus to package large DNA sequences for gene therapy was challenged; this led to a new insight which is in turn being incorporated into our gene therapy efforts. A protocol for testing the dysferlin mouse model was developed recently and is currently the only reliable method available in the field. Some of the progress has come at the expense of showing that a previous hypothesis is wrong, an “easy” path to a therapy is blocked by a daunting technical hurdle, or a simple model of how this disease manifests is more complex than previously thought.

There is comfort in knowing that although some of these things fall away as erroneous, impractical or impossible, the knowledge that we are gaining from trying these avenues will ultimately guide us closer to a therapy.