Probiodrug provides further insights into the onset of AD in The Journal of Neuroscience
Halle/Saale, September 8th 2011 — Probiodrug AG (Probiodrug), a biotech company developing novel products for the treatment of neurodegenerative and inflammatory disorders, today announced the publication of data providing key insights into the onset and development of Alzheimer?s disease (AD) in the Journal of Neuroscience.
AD is characterized by deposition of amyloid-ß (Aß) plaques in the brain. However, quantitative relationship between plaque deposition and severity of cognitive decline in the affected individuals is still elusive. Often, elderly people carry a large amyloid burden without any signs of cognitive impairments, and many animal models of AD also develop the characteristic hallmarks, such as plaques, but do not demonstrate the cognitive defects and loss of neurons typical of the human disease.
Several years ago, Probiodrug developed the hypothesis that the missing link between Aß load and prevalence of AD is a certain modification of Aß, in which the Aß molecule carries a pyroglutamate residue (pGlu) at its N-terminus. This pGlu-Aß is neurotoxic and develops a strong tendency to aggregate and to seed aggregation of further pGlu-Aß as well as unmodified Aß. The modification of glutamic acid to a pGlu-residue is catalyzed by the so-called QC enzyme (glutaminyl cyclase).
In The Journal of Neuroscience Probiodrug researchers (and their collaborators from Friedrich Alexander University, Erlangen, the German Center of Neurodegenerative Diseases, Magdeburg, the Leibniz Institute for Neurobiology, Magdeburg, the Paul Flechsig Institute for Brain Research, Leipzig, and the University of Tennessee, Knoxville/ USA) now describe the generation and characterization of a novel animal model that solely expresses N-truncated human Aß, which in turn is modified by QC to pGlu-Aß. As a result, these animals which express the toxic species 1000 fold less than other models do with Aß not only have the typical pathological changes, but also neuronal loss and cognitive impairments.
“We now have animal models that represent the full spectrum of pathological and behavioral changes in AD without overexpressing the Aß peptides. In addition, we could once again clearly demonstrate that the activity of QC enzymes is starting the chain of events that ultimately leads to the debilitating disease, which already affects millions of people world-wide. The results in this study also demonstrate that lowering the QC-dependent formation of pGlu-Aß reduces the amount of neurotoxic aggregations, and further strengthens the hypothesis that inhibition of QC is a promising new treatment strategy for AD” commented Hans Ulrich Demuth, CSO of Probiodrug.
Probiodrug is a biopharmaceutical company dedicated to the development of innovative small molecule drugs for the treatment of metabolic, neuronal and immune diseases. Probiodrug is validating novel targets to develop first and best in class therapeutics.
The Company has a dominant position in the area of glutaminyl cyclase (QC and isoQC) inhibition. These enzymes have a crucial role in the pathogenesis of Alzheimer?s disease (AD) and inflammatory disease conditions. Based on this mechanism of action, Probiodrug is currently establishing completely novel treatment schemes.
Probiodrug’s expertise is based on its unique track record in the elucidation of the structure and function of enzymes which play a central role in the maturation of hormones. The Company has pioneered the field of DP4 inhibition for the treatment of type 2 diabetes. Compounds and technology patents of its DP4 (dipeptidyl peptidase 4) program in diabetes were licensed to various pharmaceutical companies. In 2004, all metabolic assets were sold to OSI Pharmaceuticals Ltd (now Astellas). The corresponding technology patents were recently acquired by Royalty Pharma. The first drug based on Probiodrugïs technologies reached the market in late 2006 and is generating blockbuster sales. Proceeds of the various transactions have been reinvested to fund a novel approach for the treatment of AD and inflammatory diseases.
The Company was founded in 1997 by Dr Konrad Glund and Prof Dr Hans-Ulrich Demuth. Since 2007, Probiodrug has raised EUR 56 million in two financing rounds to advance its Alzheimer / neurodegenerative diseases program based on the glutaminyl cyclase (QC) target. Probiodrugïs investors include institutions such as BB Biotech, Edmond de Rothschild Investment Partners, Goodvent/IBG, HBM, TVM, Life Sciences Partners, BiogenIdec Ventures, CFH Group, and private investors. Probiodrug is located in Halle/Saale, Germany, and operates a subsidiary in Martinsried, Germany. For more information, please visit www.probiodrug.de.
Dr. Kumar Srinivasan
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Dr. Ludger Weß
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