STOCKHOLM, Sweden, Nov. 4, 2003 (PRIMEZONE) -- An international research group, including among other authors Professor Philippe Froguel (Pasteur Institute, Lille, France) and Professor Ake Lernmark (University of Washington, Seattle, USA) report that the activity of GAD genes is strongly related and explain why some patients have eating disorders and become obese. Diamyd Medical licenses the therapeutic applications of the GAD gene from the University of California in USA.
"As the company understands it, GAD gene therapy might be used for treatment of anorexia eating disorders. Diamyd Medical licenses a dominant patent from UCLA, USA, for therapeutic purposes which includes such an application. It is too early to speculate as to what impact these new research findings will have for the company," says President Anders Essen-Moller. "The new findings further strengthen the importance of GAD in metabolic disorders, where autoimmune diabetes may follow."
The research results were published yesterday in the journal Public Library of Science Biology.
While extreme obesity is thought to be the combined result of a variety of genetic and environmental factors, the GAD gene is the first gene implicated as a strong candidate gene in conditions of abnormal weight.
The GAD2 gene codes for GAD65, an enzyme which increases production of the neurotransmitter GABA. When GABA interacts with another molecule, neuropeptide Y, in a specific part of the brain (the paraventricular nucleus of the hypothalamic), food intake is stimulated.
Researchers believe that individuals with a more active form of the GAD gene accumulate a larger pool of GABA in the hypothalamus, and this explains why obese individuals overeat.
GAD gene therapy is currently tested in treatment of both Parkinson's disease and epilepsy.
GAD65 is the most important antigen in autoimmune diabetes. Diamyd Medical have shown that administration of a novel therapeutic DiamydTM, a recombinant GAD65 protein formulated in aluminum hydroxide, significantly improves production of insulin after 6 months in a Phase II clinical trial involving Type 2 diabetics with GAD auto antibodies. Diamyd Medical actively seeks partnership with an established pharmaceutical company for further development and marketing of this recombinant therapeutic.
More about the GAD2 gene and obesity
GAD65 catalyses the formation of GABA from L-glutamate, and is expressed in both the central nervous system and in the insulin-producing cells of the pancreas. GABA is localized together with neuropeptide Y in nerve cells and is involved in the reaction of leptin in the hypothalamus (Ovesjo 2001).
Increased activity of the GAD2 gene leads to increased levels of GAD65 and GABA. Together with neuropeptide Y, GABA stimulates appetite (Pu 1999).
Dopaminergic nerve cells have previously been proposed to be involved in eating disorders. Dopaminergic signals regulate the activity of the GAD2 gene and consequent production of GAD65 and GABA (Laprade 1999). A relationship thus exists between the dopamine system and GAD.
Not only a central role of GAD65 in development of obesity but also a peripheral role can be envisaged. Each pancreatic insulin-producing beta cell contains approximately 3000 microvesicles containing GABA as a consequence of GAD65 activity. When GABA is released the release of insulin from beta cells and glucagon from alpha cells ceases (Rosman 1989). As insulin and glucagon have an anorexic effect in the brain, the GAD2 gene, being responsible for GABA and GAD65 production, also stimulates appetite in obese individuals (Niswender 2003).
Previous studies have shown that obesity is associated with mutations in the leptin-melanocortin cascade (Clement 2002). Frogeul's results implicate the importance of the GAD2 gene in development of obesity, where GABA in neuropeptide Y nerve cells regulates the anorexic release of insulin from beta cells (Schwartz 2003).
About Diamyd Medical:
Diamyd Medical's business idea is the identification and development of pharmaceutical projects up to and including Phase II studies. Diamyd Medical is at present running a number of GAD-based development projects and has licensed the rights to these from universities in the US. The Company's project that has come farthest is a vaccine for insulin- dependent diabetes. Positive results from a Phase II study with the diabetes vaccine have been reported.
For more information contact: Anders Essen-Moller, Diamyd Medical AB (publ) (corporate. id. No.: 556530-1420) Djurgardsbrunnsvagen 54, SE-115 25 Stockholm, Sweden. Tel: +46 (0)8-661 00 26, 661 12 25, fax: +46 (0)8- 661 63 68 or email: info@diamyd.com
This report is a translation from an original in Swedish. No guarantee is given or implied for the accuracy of statements concerning present or historical data, future results and prognoses.
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