IETF Funded Research 2010
Towards the Identification of the Anti-Tremor Target of Low-Dose Alcohol
Dr. Charles Handforth, Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, was awarded $50,000 for the study “Towards the Identification of the Anti-Tremor Target of Low-Dose Alcohol”.
In this ground-breaking study, Dr. Adrian Handforth discovered that the GABA type A receptor is a pentamer composed of two alpha, two beta and either a gamma or a delta subunit. There are 6 types of alpha subunits, 3 types of beta, 3 types of gamma, but only one delta subtype. Delta GABA receptors are a minority but because they are non-desensitizing and act tonically rather than phasically their physiological importance is greater than their numbers may suggest. When Dr. Handforth became aware of reports that low-dose alcohol acts preferentially on delta GABA receptors, he wondered whether they might represent a viable anti-tremor target.
Although some pharmaceuticals are working with delta GABA receptor agonists, and have reported preclinical evidence for anxiolytic effects, to our knowledge there are no delta agonists on the market. Preliminary findings offer the interesting possibility that a drug acting preferentially on the alpha6-delta receptor may be effective yet well tolerated in view of its select location in the cerebellum.
Deep Cerebellar Nuclei of Essential Tremor Patients: Postmortem Investigations
A $25,000 grant is to go to Dr. Frederic Calon, Centre de recherché du CHUL, Quebec, Canada for the study GABA Abnormalities in “Deep Cerebellar Nuclei of Essential Tremor Patients: Postmortem Investigations”.
Owing to the small number of clinicopathological studies, our understanding of the pathophysiology (pathophysiology seeks to explain the physiological processes or mechanisms whereby such condition develops and progresses) of essential tremor has lagged behind other Central Nervous System (CNS) diseases. The present investigation is probably the first to report a neurochemical difference in individuals with essential tremor, versus controls or patients with Parkinson’s disease, using human brain tissue. Since GABAergic input into deep cerebellar nuclei neurons is critical for the regulation of its pacemaker activity extending through cerebellothalamo-cortical networks, a reduction of GABA receptors may play an important role in the generation of tremor. Finally, our results suggest that GABA receptors within the deep cerebellar nuclei are potential drug targets in essential tremor.