Spinocerebellar ataxia type 3 (SCA3), caused by a CAG repeat expansion in the ataxin-3 gene (ATXN3), is characterized by neuronal polyglutamine (polyQ) ATXN3 protein aggregates. Although there is no cure for SCA3, gene-silencing approaches to reduce toxic polyQ ATXN3 showed promise in preclinical models. However, a major limitation in translating putative treatments for this rare disease to the clinic is the lack of pharmacodynamic markers for use in clinical trials. Here, we developed an immunoassay that readily detects polyQ ATXN3 proteins in human biological fluids and discriminates patients with SCA3 from healthy controls and individuals with other ataxias. We show that polyQ ATXN3 serves as a marker of target engagement in human fibroblasts, which may bode well for its use in clinical trials. Last, we identified a single-nucleotide polymorphism that strongly associates with the expanded allele, thus providing an exciting drug target to abrogate detrimental events initiated by mutant ATXN3. Gene-silencing strategies for several repeat diseases are well under way, and our results are expected to improve clinical trial preparedness for SCA3 therapies.

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Sudden unexpected death in epilepsy (SUDEP) is a devastating direct epilepsy-related cause of death. Although its occurrence has some risk factors, it is unanticipated and very traumatic to the families of affected patients. Effective preventive measures for SUDEP are lacking; therefore, efforts are directed at modifiable risk factors. The majority of caregivers of patients with epilepsy and SUDEP wish they would have known more about the topic before the terminal event. SUDEP is a difficult topic for physicians and clearly even more challenging to discuss with patients and caregivers. The pathophysiology of SUDEP is controversial, but awareness should be raised despite individual opinions. During the last decade SUDEP has received substantial attention, and efforts are being made to increase worldwide awareness. The American Epilepsy Society and Epilepsy Foundation Joint Task force, National Institute for Health and Care Excellence, and the Scottish Intercollegiate Guidelines Network recommend educating patients about SUDEP. Education will potentially help meet treatment goals, promote better patient-physician rapport, decrease anxiety and fear, serve as a filter for inaccurate information, and lessen grief and blame in the families of patients affected by SUDEP. This article will cover a literature review on SUDEP, epidemiology, risk factors, proposed mechanism, potential interventions, physician practices and suggested measurements, and public websites designed to increase SUDEP awareness.

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