A drug discovery and development collaboration between leading Australian Institutions, the Children's Medical Research Institute (CMRI), University of Newcastle, University of Melbourne and Bio-Link Partners Ltd., has been announced as the Epilepsy Therapy Project, June 2008 New Therapy Grant winners. This prestigious research grant recognises their promising drug discovery program, which is focussed on development and commercialisation of small molecule inhibitors of the GTPase Dynamin, a key component of the synaptic vesicle cycle and a novel approach to treatment of epilepsy.
The two year US$278,800 grant to the Dynamin Drug Discovery Program will support the refinement of lead classes of inhibitors which have demonstrated efficacy in animal models towards clinical development and commercialisation. The Dynamin Drug Discovery Program consists of leading expertise in synaptic vesicle endocytosis and dynamin biology, medicinal chemistry and translational studies in acquired epilepsy models. Award of the New Therapy Grant recognises the potential of dynamin as a new molecular target for the design of a new class of therapeutics to treat epilepsy. In announcing the award, Joyce Cramer, President of the Epilepsy Therapy Project said " The Australian group exemplifies the ideal of collaboration among experts to work on a novel approach to limiting seizure propagation. We are eager to watch their progress toward human studies that will reveal the full potential of this effect on brain signaling".
The Epilepsy Therapy Project seeks to advance the development of new therapies for epilepsy, including new medicines and therapeutic devices. The grants committee consists of leading opinion leaders in the fields of epilepsy clinical practice and anti-epileptic drug (AED) research. The Program attracts applications from leading research groups and biotech companies worldwide. Consistent with the theme of translational research, all grant proposals must 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 the Anticonvulsant Screening Program at the US National Institute of Neurological Disorders and Stroke and the O'Brien group have provided deep insights and capabilities in in vivo screening in a large range of different seizure models. Associate Professor O'Brien also provides clinical insights and expertise for lead selection and clinical testing. The Program technology is protected by an expanding patent estate covering broad composition of matter and method of use patents over compound and peptide classes and assay technologies. Overall, the Program represents a unique capability to exploit the potential of Dynamin as a novel therapeutic target for epilepsy.
Approximately one in 120 people have epilepsy, while up to 5% of the world's population may have a seizure at some time in their lives. Epilepsy is diagnosed when seizures are unprovoked and recurrent. Approximately only 70% of patients with epilepsy benefit from current treatments. There is a large unmet medical need for new therapeutic approaches to help those patients that do not receive benefit from current treatments, or suffer from undue side effects.
The Epilepsy Therapy Project is a 501 (c) (3) not-for-profit corporation dedicated to a singular focus: overcoming the funding gaps and roadblocks that slow the progress of new therapies from the lab to the patient. Epilepsy Therapy Project seeks to improve incentives and encourage commercial investment in new therapies. Acting as both a catalyst and clearing house for innovative research and the early commercialization of new therapies, the Epilepsy Therapy Project brings together financial resources, scientific insights and business expertise from leading academic and commercial industry participants. This New Therapy Grant is sponsored by Finding A Cure For Epilepsy and Seizures (f.a.c.e.s), a partner of the Epilepsy Therapy Project. See www.epilepsy.com/epilepsy_therapy_project
The Children's Medical Research Institute researches genes vital for children's health and development, and the causes of genetic childhood diseases such as epilepsy, cleft lip and palate and cancer. CMRI's results help develop better treatments, cures and preventions for childhood diseases. This Sydney-Australia based, not-for-profit organisation is funded by competitive grants and Jeans for Genes Day. See www.cmri.org.au
The University of Newcastle is a national and international leader in research and discovery. Ranked in Australia's top 10 universities for research, its strengths lie in the universally vital areas of health, energy and the environment, and science and engineering. The University of Newcastle is also widely recognised for progressive teaching and learning, providing its 26,000 undergraduate and postgraduate students with the latest in contemporary teaching practices. Problem-based learning, first pioneered by the University some 25 years ago, forms the basis of programs in medicine, engineering, architecture, nursing and law. See http://www.newcastle-edu.com
The University of Melbourne's Department of Medicine (RMH/WH) is a large clinical-based department that conducts research and teaching across such areas as Arthritis and Inflammatory Diseases, Epilepsy and Neuropharmacology, Gastrointestinal Cancer, Endocrinology, Genes and Environment, Hepatitis, International and Immigrant Health, Malaria, Rheumatic Diseases and Rheumatology. See http://www.medrmhwh.unimelb.edu.au/
Bio-Link is a life sciences commercialisation company which facilitates biotechnology commercialization based on technology review, project management, business development and deal negotiation. Bio-Link has offices in Sydney and Melbourne, Australia, and has academic and biotech clients throughout Australia and internationally. Bio-Link adds value to the commercialization process through critical assessment of patents, packaging of pre-clinical and clinical data, development of commercialization strategies, technology marketing, and identification and engagement with potential collaborators, licensees, or investors. Bio-Link was originally supported with funding from the New South Wales Office of Science and Medical Research to provide commercialization services to New South Wales medical research institutions. See www.bio-link.com.