Strong correlation between QCs and AD pathology in human brain biopsies underlines QC-inhibition as therapeutic approach
HALLE/SAALE, Germany, 3 March 2015 – Probiodrug AG (“Probiodrug”, Euronext: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer’s disease (AD), is pleased to note that a recently published paper in the journal Acta Neuropathologica[1] further details the role of Glutaminyl Cyclases (QCs) in AD pathology. The findings from the publicly funded research that included Prof Hans-Ulrich Demuth (as CSO of Probiodrug)[2] and Prof Steffen Roßner[3] show that besides QC, as shown earlier, its sister enzyme isoQC also contributes to Abeta pathology and neuroinflammation.
Data obtained in a transgenic animal model show co-expression of isoQC with its substrate, the chemokine CCL2, which is increased upon stimulation by pGlu-Abeta in brain astrocytes supporting earlier data obtained by Probiodrug. The research groups could now show for the first time that in brains of AD patients the expression of isoQC and CCL2 mRNA and protein is up-regulated as compared to age-matched controls, and correlates with pGlu-Abeta load and with the decline in mini-mental state examination as a measure of cognitive functions.
Prof Hans-Ulrich Demuth, co-author of the study said: “These data are important for the understanding of QC/isoQC’s roles in the vicious cycle of toxic pGlu-Abeta formation and chronic neuroinflammation.”
Dr Inge Lues, Chief Development Officer of Probiodrug, added: “Probiodrug’s spearheading small molecule QC-inhibitor PQ912, currently in Phase 2a clinical study, inhibits both isoforms of QC with similar potency. These data highlight that QC-inhibition is a double pronged approach by not only tackling the formation of toxic pGlu-Abeta but also by interfering with the inflammatory chemokine CCL2.”
1 Hartlage-Rübsamen et al.: Isoglutaminyl cyclase contributes to CCL2-driven neuroinflammation in Alzheimer’s disease. Acta Neuropathol, DOI 10.1007/s00401-015-1395-2.
2 Now: Fraunhofer Institute for Cell Therapy and Immunology IZI Leipzig, Leipzig, Germany
3 Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, 04109 Leipzig, Germany
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For more information please contact:
Dr Konrad Glund, CEO, Probiodrug
Email: contact@probiodrug.de
Hume Brophy
Email: probiodrug@humebrophy.com
Tel: +44 (203) 440 5653
Notes to Editors:
About Probiodrug AG
Headquartered in Halle, Germany, Probiodrug AG is a biopharmaceutical company focused on the development of new therapeutic products for the treatment of Alzheimer’s disease.
Founded in 1997, the company successfully developed a novel therapeutic concept for diabetes – the DP4 inhibitors – which provided the basis for a novel class of antidiabetics – the gliptins. Its core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes involved in the modification of proteins and peptides, which play a central role in pathological conditions.
Today Probiodrug’s aim is to become a leading company in the development of Alzheimer’s disease treatments and to thereby provide a better life for Alzheimer’s disease patients. It has identified a new therapeutic concept linked to disease initiation and progression. The development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight Alzheimer’s disease. The Company has medical use and composition of matter patents related to the inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific monoclonal antibodies, providing it, in the Company’s view, with a leading position in this field of research. www.probiodrug.de
About Alzheimer’s disease
Alzheimer’s disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Because Alzheimer’s disease cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance. Today, over 35 million people worldwide currently live with the condition and this number is expected to double by 2030 and to more than triple by 2050 to 115 million (World Alzheimer Report 2013).
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