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Dynamin drug discovery team win prestigious international epilepsy grant
Date:6/18/2008

demonstrate a clear path from the lab to the patient.

A common feature of all AEDs is a reduction in synaptic transmission. The GTPase Dynamin represents a potentially highly efficacious target that indirectly modulates neurotransmitter loading, leading to reduced epileptic synaptic transmission, while limiting potential side effects. Dynamin mediates synaptic vesicle endocytosis (SVE), a process which replenishes synaptic vesicles prior to reloading and subsequent neurotransmitter release. Modulation of Dynamin limits the efficiency of SVE to retrieve vesicles, decreasing the rate at which neurons can recycle them to sustain synaptic transmission. Hence seizure activity is minimized through depleting the sustainability of neuronal burst firing, without directly influencing the synaptic transmission process. During regular physiological conditions synaptic transmission does not rely on such rapid vesicle replenishment limiting potential mechanistic side effects.

The Dynamin Drug Discovery Program represents an extensive collaboration between Professor Phil Robinson, CMRI (Dynamin Biology), Associate Professor Adam McCluskey, University of Newcastle (Medicinal Chemistry), Associate Professor Terence O'Brien, University of Melbourne, Department of Medicine, Royal Melbourne Hospital (Translational Models) and Bio-Link Partners Ltd. (Commercialization Strategy and Implementation). The program consists of an iterative drug discovery and development cycle for development of dynamin inhibitors as novel therapeutic candidates for epilepsy, other CNS disorders and cancer. The Robinson group originally cloned the human dynamin 1 isoform, and are leaders in the understanding of its biological functions and development of in vitro and cell function assays. In conjunction with the medicinal chemistry expertise of the McCluskey group, a large number of classes of small molecule and peptide inhibitors of dynamin have been developed. Ongoing collaborations with
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Contact: Jens Tampe
j.tampe@bio-link.com
61-292-094-381
Research Australia
Source:Eurekalert

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