Using Genetics to Identify New Treatments for Episodic Disorders

"We might be able to identify a completely new target for treating episodic diseases like migraine and epilepsy." Louis Ptáček, MD

Dr. Louis Ptáček is using his Weill Scholar Award to try to uncover the normal role of a newly discovered causative gene in patients with paroxysmal non-kinesigenic dyskinesia (PNKD). While the episodic movement disorder is extremely rare, Dr. Ptáček believes that understanding how this particular gene functions might open up new treatment options for patients with PNKD and a host of other movement disorders. As the world’s leading expert in PNKD – by his estimate, he’s seen three times as many patients with the disease than any other physician – you would be hard pressed to find a better person for the job.

The origin of his interest in episodic disorders: After my neurology residency, I treated a patient with muscular dystrophy in a large Utah family. I went on to see 100 people in the family, 40 of whom were affected by this rare disorder. It’s a fascinating disorder in which patients can become periodically paralyzed but are otherwise normal. That’s a trait that is shared by other episodic diseases like epilepsy, migraine, and cardiac arrhythmias, as well as PNKD, the disease I’m studying with my Weill Award.”

On the importance of studying rare disease: “You can’t ignore a problem because it doesn’t happen very often. If you or someone you love has PNKD, it’s incredibly significant. Moreover, episodic diseases have many clinical similarities. Patients often are completely normal between attacks, but environmental stressors push them over the edge. With this work, we might be able to identify a completely new target for treating episodic diseases, a whole new way to think about how to develop better drugs that help patients not just with this disease but also with other more common disorders like migraines or epilepsy.”

The discoveries that have paved the way for this work: “The protein we’re studying is similar to an enzyme in a stress-response pathway. That’s interesting because PNKD is an episodic disease, so people are doing well much of the time but experience attacks while under different forms of stress. Separately, to try to better understand what this protein is doing, we’re also looking to see what other proteins it interacts with. As part of this investigation, we’ve identified a totally new synaptic protein, now called PNKD, which appears to be a causative gene for this disease.”

Why this work is happening now: “I submitted a grant request to the National Institutes of Health five years ago, and they said ‘Oh, this is great, but it’s a rare disease, so why should we even bother?’ Of course, I tried to make the case for how this disease could help us understand other more common diseases, but I was unsuccessful. When the Weill Award opportunity came up, I was immensely excited because I thought, ‘Wow, maybe we can go back to this question and do this work.’”

Why UCSF: “There is no place in the world better than UCSF for the depth and breadth of its neuroscience community. It is a tremendously rich environment in which to embark on deeper biological studies, where we have great colleagues with whom we collaborate, get advice from, and learn from. We also have resources here – access to hundreds of patients with this rare disease – that no one else has at their disposal.”