Nematode Neuromuscular Junction GABA Receptors and Related Methods
The major inhibitory neurotransmitter in the brain is ?-aminobutyric acid (GABA), which primarily acts through GABAA receptors. Defective GABA neurotransmission causes neurological diseases such as anxiety disorders and epilepsy. GABAA receptor (ca 250 kD) is a ligand-gated chloride channel formed by five homologous subunits. Binding of GABA to the receptor opens the channel, causing an increase in the chloride permeability of the plasma membrane, which in turn reduces cellular excitability. In contrast to vertebrates where the majority of action of GABA is at the synapses of the central nervous system, in nematodes GABA acts primarily at the inhibitory neuromuscular synapses. Bamber and colleagues at the University of Utah have identified the gene and cloned the C. elegans GABA receptors. In addition they have developed high through-put In vivo screening assays using C. elegans phenotypes.
GABA receptors have considerable medical and economic importance. In humans, these are targets of many drugs that reduce neuronal excitability. Such drugs are used to treat anxiety, epilepsy and insomnia. The antipsychotic market is worth an estimated $10.7 billion. In invertebrates, these receptors are the targets of pesticides and anti-parasitic compounds used in agriculture and medicine. Nematodes that parasitize plants cause an estimated $8 billion annual loss to U.S. growers.
Stage of Development
Two patents (6,407,210 and 6,406,872) have been issued by the USPTO. A third application that has been published with publication number US20030065144A1.
This technology is part of an active and ongoing research program and has been demonstrated to work in proof-of-concept experiments which includes a working prototype has been validated in animal experiments It is available for licensing under either exclusive or non-exclusive terms.
*Bamber BA, Twyman RE, Jorgensen EM. (2003) Pharmacological characterization of the homomeric and heteromeric UNC-49 GABA receptors in C. elegans. Br J Pharmacol. 138(5):883-93.
Bruce Bamber, Roy Twyman, Erik Jorgensen, Asim Beg
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