Novel signaling pathways and therapeutics for the treatment of epilepsy
Epilepsy is a crippling disease that affects approximately 1% of the world’s population and has an annual economic burden of over $12.5B. The majority of costs are concentrated in patients with medically-intractable forms of this disease, which includes medically-refractory temporal lobe epilepsy (TLE). The dearth of treatments for TLE is primarily a result of a lack of understanding of the molecular mechanisms associated with this disease, and comprehension of these would likely lead to more treatment options.
Dr. James McNamara and colleagues have recently identified the brain-derived neurotrophic factor receptor (BDNF) tyrosine kinase, TrkB, as a druggable target for the treatment of TLE. Supported by the fact that BDNF is overexpressed in the hippocampi of patients with this disease, Dr. McNamara et al. have developed a novel peptide, pY816, that uncouples the binding of TrkB to its downstream signaling mediators. Remarkably, in a mouse model of TLE, a modest 2-week treatment regimen with pY816 was able to diminish the number of recurrent seizures by at least 90% over a 2-week, post-treatment observation period in the majority of treated mice. These findings support the potential of pY816 to serve as a powerful new treatment option for TLE, for which very few options currently exist.
This invention is a first of its kind therapy for the treatment of TLE, which could potentially transform medically-refractory epilepsy into a medically-responsive form.