Tag: Kumar Srinivasan

Company News: Neurodegeneration in Alzheimer’s Disease: The crucial role of QC

Probiodrug provides further insights into the onset of AD in The Journal of Neuroscience

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 (http://redir.ec/jneurosci).

AD is characterized by deposition of amyloid-β (Aβ) 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 Aβ load and prevalence of AD is a certain modification of Aβ, in which the Aβ molecule carries a pyroglutamate residue (pGlu) at its N-terminus. This pGlu-Aβ is neurotoxic and develops a strong tendency to aggregate and to seed aggregation of further pGlu-Aβ as well as unmodified Aβ. The modification of glutamic acid to a pGlu-residue is catalyzed by the so-called QC enzyme (glutaminyl cyclase).

In this week’s 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 Aβ, which in turn is modified by QC to pGlu-Aβ. As a result, these animals which express the toxic species 1000fold less than other models do with Aβ 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 Aβ 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-Aβ 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.

*doi:10.1523/JNEUROSCI.2172-11.2011

Company News: Probiodrug Appoints Kumar Srinivasan as Chief Business Officer

Probiodrug (Halle, Germany) has appointed Dr Kumar Srinivasan, previously Vice President, Global Business Development at Wyeth, to Chief Business Officer. Wyeth was acquired by Pfizer in 2009. Probiodrug has a focus on neurodegenerative diseases, in particular Alzheimer’s disease. In this indication, the company pursues a novel target and pathway and is preparing for the start of clinical development of one of its lead candidates, a small molecule inhibitor of the enzyme glutaminyl cyclase (QC). Kumar Srinivasan, MBA, has a background as research chemist and is an experienced pharma / biotech dealmaker. He will be responsible for Probiodrug’s global business development activities and will be based in Philadelphia, PA. The full press release can be found here.