KeyNeurotek Pharmaceuticals AG

Magdeburg, July 10, 2008 - KeyNeurotek Pharmaceuticals AG, a biotechnology company focused on the development and marketing of drugs against autoimmune diseases and degenerative disorders of the central nervous system (CNS), today announced new data allowing important insights into the molecular causes of Huntington's Disease. For the first time, research data on this extremely disabling disease open a road to the development of a causative treatment. The findings are pre-published in the current online version of the Journal of Biological Chemistry[1], a biweekly publication of the American Society for Biochemistry and Molecular Biology. Huntington's Disease is a rare neurodegenerative disease of the human brain leading to uncontrolled movements, emotional disturbance and finally to loss of intellectual faculties. Patients usually die within 15-20 years after the onset of first symptoms. On the molecular level, it is characterized by a mutation in the so-called huntingtin gene which leads to a protein with an abnormally increased number of glutamine residues (httexpQ). The underlying pathomechanisms linking this mutation to the origination and progression of Huntington's disease, however, had remained unclear for more than a decade. Now researchers at KeyNeurotek and its long-term collaborators at the Universities of Erlangen-Nuernberg and Tuebingen (both Germany) have discovered that httexpQ specifically targets certain transport proteins of brain mitochondria. Using a new proprietary transgenic rat strain, which was generated by Prof. Stephan von Horsten and which for the first time models the adult form of human Huntington's Disease, the authors identified the so-called mitochondrial glutamate/aspartate carrier (aralar) and the permeability transition pore as specific targets of httexpQ. In addition, the researchers found that Ca2+-dependent substrate supply and consumption of brain mitochondria become severely compromised, if httexpQ interferes with its targets. Mitochondria serve as cellular power stations consuming oxygen and appropriate substrates to supply the extraordinary energy demand of neuronal brain cells with sufficient amounts of energy equivalents (ATP). Therefore, httexpQ-induced inhibition of substrate influx and ATP generation severely impairs brain mitochondria and causes a sequence of devastating events which are crucially involved in the progression of Huntington's Disease, i.e. mitochondrial dysregulation, energetic depression, neuronal cell death and tissue atrophy. "After 15 years of research on the cytotoxic actions of mutated huntingtin, these findings for the first time not only provide a new basis for the understanding of Huntington's Disease but also for the development of a causal treatment", said Dr Frank Gellerich, Head of the Department of Energy Metabolism at Keyneurotek and lead author of the study. "This breakthrough discovery has been possible thanks to a long-standing and productive collaboration with our academic partners in Erlangen and Tuebingen." "These findings once again underline our strong research capabilities and our expertise in CNS-related diseases", Dr Frank Striggow, CEO of KeyNeurotek Pharmaceuticals added. "Besides, the energy metabolism is key to understanding other chronic CNS diseases, e. g. Alzheimer's and Parkinson's Disease, and ageing. We therefore believe that our research provides us with various opportunities for the development of novel treatment strategies in the area of neurodegenerative diseases."