Halle/Saale, July 8, 2010 — Probiodrug AG (Probiodrug), a biotech company developing novel concepts and products for the treatment of neurodegenerative and inflammatory diseases with a particular focus on Alzheimer’s disease, today announced that the Company will present four posters featuring its latest research results about a unique pathway possibly involved in the onset and progression of Alzheimer’s disease at the upcoming International Conference on Alzheimer’s Disease (ICAD, July 10-15) in Hawaii (USA).
The findings that not all of the amyloid beta protein, which is in the focus of Alzheimer research for decades, but only a particular, pyroglutamated version of it, is toxic, highly abundant in the brain of Alzheimer patients and can – at least in animal models – be attenuated by either passive immunization or by inhibition of the enzyme producing this modification, has been selected for presentation in this year’s Hot Topics Poster Session.
The enzyme in question is glutaminyl cyclase (QC), an enzyme catalyzing the formation of pyroglutamic peptides or proteins from an N-terminal glutamine residue. While it was assumed for a long time following their discovery that the QC enzymes show a strict specificity for glutamine in the N-terminal position of peptides and proteins, Probiodrug discovered that all (plant, bacterial and mammalian) QCs can perform under certain conditions also the conversion of a N-terminal glutamate to form the so-called pyroglutamated (pGlu) peptide species. In addition, the Hot Topic Poster presents for the first time, that the neurotoxicity of the pGlu-Abeta peptide driven oligomer formation is strictly Tau-protein dependent.
The poster selected for the Hot Topics session on July 14, 11:30 AM – 1:00 PM is authored by Hans-Ulrich Demuth, CSO and co-founder of Probiodrug and two Alzheimer specialists from the US: George S. Bloom, Professor of Biology and Cell Biology at the University of Virginia, Charlottesville, VA, and Cynthia Lemere, Associate Professor of Neurology at Brigham and Women’s Hospital and the Center for Neurologic Diseases at Harvard Medical School, Boston, MA.*
Alzheimer’s disease (AD) is characterized by the accumulation of neurotoxic plaques in the brain of AD patients. It has been discovered by Probiodrug and others that Aß peptides carrying an N-terminal pyroglutamic residue are prone to form seeds of already early and intraneuronal depositions long before the plaques’ occurrence. These modified peptides are formed through a hitherto unknown catalytic activity of the enzyme glutaminyl cyclase (QC). In addition, these N-truncated and modified peptides initiate early neuroinflammation, which is also driven by glutaminyl cyclases.** Based on these findings, Probiodrug has developed a novel therapeutic concept for AD involving small molecule inhibitors of QC.***
* Poster P4-094 by Hans-Ulrich Demuth, George S. Bloom, Cynthia A. Lemere: Pyroglutamated ß-amyloid is toxic, highly abundant in Alzheimer’s brain, amplifies tau-dependent ß-amyloid cytotoxicity and can be attenuated by passive immunization or inhibition of glutaminyl cyclase.
**Poster P1-323 by Holger Cynis, Sigrid Graubner, Anca Alexandru, Kathrin Gans, Stephan Schilling, Hans-Ulrich Demuth: Distinct role of glutaminyl cyclases (QCs) in inflammation/neuroinflammation: First results from QC and isoQC knock out mice.
***Poster P3-407 and P3-412
Probiodrug is a biopharmaceutical company focused on the development of innovative small molecule drugs for the treatment of neuronal and inflammatory diseases. In these areas, Probiodrug is validating new targets with the prospect of first and best in class therapeutics. The Company has a dominant position in the area of glutaminyl cyclase (QC) inhibition, an enzyme emerging with a crucial role in the pathogenesis of Alzheimer’s disease (AD) and various additional inflammatory conditions. In addition, the Company is pursuing further novel approaches in the area of inflammatory diseases.
Probiodrug’s core expertise is based on its long-standing, unique experience with the structure and function elucidation 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. The first drug based on Probiodrug`s technologies reached the market in late 2006. Proceeds of the various transactions have been reinvested to fund the novel approach for the treatment of AD.
The Company was founded in 1997 by Prof Dr Hans-Ulrich Demuth and Dr Konrad Glund. Probiodrug has raised EUR 56 mio for its QC program so far, with the last round being closed end of 2009. In 2007, the company acquired Ingenium Pharmaceuticals AG; Hendrik Liebers joined the company as CFO the same year. Probiodrug is located in Halle (Saale), Germany, and operates a subsidiary in Martinsried/Munich, Germany. For more information, please visit www.probiodrug.de.
Prof Dr Hans-Ulrich Demuth
Vice-CEO and CSO
D-06120 Halle/ Saale
Tel.: +49 345 55599-00
Fax: +49 345 55599-01
Dr Ludger Weß
Saseler Loge 6b
Tel.: +49 40 88 16 59 64
Fax: +49 40 88 16 59 65