Technologies

Currently, millions of Americans suffer from epilepsy and fully 1/3 of these patients do not respond to available treatments. Researchers at Brandeis University have discovered that the Sema4D-PlexinB1 interaction may be harnessed as a novel strategy for the treatment of seizure disorders.
A key aspect of neuronal circuit formation is achieving the proper balance of excitation and inhibition (E/I) within the circuit. A given neuron, through its synaptic connections, either excites or inhibits other neurons in the circuit, thus establishing this balance. Disruptions to the E/I balance can have pathological consequences for circuit function as demonstrated by the manifestation of devastating neurological disorders, including epilepsy and Autism Spectrum Disorders (ASD).
The current invention is a novel approach to treating disorders such as epilepsy that would restore the normal E/I balance in network activity bypermanently increasing the number of inhibitory synapses. Treatment of hippocampal cultured neurons with the protein Sema4D, acting through its receptor PlexinB1, causes a rapid increase (i.e. within 30 minutes) in the density of functional GABAergic synapses. It was also discovered that Sema4D could rapidly drive inhibition in the context of aberrant neuronal hyperexcitability induced in an organotypic hippocampal slice culture model of epilepsy. Researchers demonstrated that acute Sema4D treatment rapidly (within 2 hours) abates the hyperexcitability found in these slices.