Probiodrug to Present Novel Causative Treatment Approach for Alzheimer’s Disease QC Inhibition To Be Discussed at Alzheimer's Association International Conference on Alzheimer's Disease (ICAD) 2008
HALLE/SAALE, Germany, July 7, 2008 -- Probiodrug AG
(Probiodrug), a developer of small molecule inhibitors for the
treatment of inflammatory and neurodegenerative diseases, announced
today that the company has been invited to present its findings
that inhibition of the enzyme Glutam(in)yl Cyclase in vivo can be
considered as a potentially causative new treatment of
neurodegeneration in Alzheimer’s Disease (AD).
On July 29, Hans-Ulrich Demuth, CSO of Probiodrug will present an
overview of the results supporting the company’s hypothesis,
that the enzyme Glutam(in)yl Cyclase (QC) plays a major role in
initiation and progression of Alzheimer’s disease and may
therefore represent a promising target for a causative treatment of
AD.
“Today, there are only treatment options available to
temporarily slow down progression of Alzheimer’s
disease”, Demuth said, “and so far all efforts to come
up with a disease modifying treatment have failed. There are a lot
of approaches aiming at the plaques and tangles found in brains of
AD-patients, but no attempt to break down these structures or to
prevent their formation has been successful.” Probiodrug
believes that it has identified a causal mechanism explaining
plaque formation as well as neurotoxicity and neuron loss in the
brain of AD patients, thereby providing a starting point to stop or
prevent plaque formation and neurodegeneration. “We have
compelling evidence suggesting that a certain variation of the beta
amyloid peptide, i. e. a pyroglutamyl-modified beta amyloid plays a
major role in Alzheimer’s disease”, Demuth added.
“The variation is caused by a cyclization of an N-terminal
glutamate residue of the peptide. As a result, the
modified peptide is uncharged, and thus hydrophobic and degradation
resistant and it exhibits a very strong tendency to
aggregate.”
In addition, its occurrence correlates with dementia in AD patients
and neuron loss in animal models. While plaques frequently present
in the brain of non-demented elderly consist primarily of
full-length amyloid beta, the plaques of AD patients mainly consist
of pyroglutamated amyloid beta peptides. Moreover, the modified
peptide unfolds profound seeding capacity, thus forming the core of
plaques found in AD patients’ brains.
”We have elucidated the molecular mechanism that leads to the
formation of the pyroglutamated amyloid beta”, Demuth said,
“and found that an enzyme called Glutam(in)yl Cyclase, or QC
performs the glutamyl cyclization activity. Since then, we have
conducted several studies applying QC inhibitors to murine models
of AD and found that the treatment reduced not only the
pyroglutamated variety but concomitantly also the full-length
peptides in the plaques and that it led to profound cognitive
improvement.” ICAD is the world's leading forum on dementia
research. The 2008 conference will take place July 26-31, 2008 in
Chicago and will be joined by more than 5,000 world-renowned
researchers.
About Probiodrug AG:
Probiodrug is a biopharmaceutical company specialized on the
development of innovative small molecule drugs for the treatment of
neuronal, inflammatory, and autoimmune diseases. In these areas,
Probiodrug is focusing on innovative targets with the prospect of
first and best in class therapeutics. The Company has a dominant
position in the area of glutaminyl cyclase inhibition, an enzyme
central for the pathogenesis of AD. In this field, Probiodrug is
pioneering a completely novel therapeutic approach. In addition,
the company is pursuing further novel approaches in the area of
inflammatory diseases. Probiodrug has generated evidence that
glutaminyl cyclase, an enzyme that cyclizes N-terminal glutamine of
peptides to pyroglutamate (pGlu), is massively overexpressed in the
brain of patients with Alzheimer’s disease (AD). The company
has also demonstrated that pyroglutamated derivatives of the
amyloid beta (A?) peptide are much more toxic and
degradation-resistant than unmodified A? peptides and that they
form the very seeds of the typical A? aggregates like AD plaques
seen in the brain of AD patients. Moreover in animal models of AD,
inhibitors of QC reduce both pGlu-A? and total A?, and improve
memory. Probiodrug`s core expertise is based on its long-standing,
unique experience with the structure and function elucidation of
enzymes central for 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) Prosidion. The first drug based on Probiodrug`s
technologies reached the market in late 2006. The proceeds of these
transactions have been reinvested to fund the novel approach for
the treatment of AD. The Company was founded in 1997 by Dr Konrad
Glund and Prof Dr Hans- Ulrich Demuth and has raised a total of $52
million. In 2007, it acquired Ingenium Pharmaceuticals AG. The
company is located in Halle (Saale), Germany, and operates a
subsidiary in Martinsried/Munich, Germany. For more information,
please visit www.probiodrug.de. Contact:
Dr Konrad Glund, CEO Probiodrug AG Weinbergweg 22 D-06120 Halle/ Saale Germany
Tel.: +49 345 55599-00 Fax: +49 345 55599-01 Mail: konrad.glund@probiodrug.de
Dr Ludger Weß akampion Saseler Loge 6b D-22393 Hamburg Germany
Tel.: +49 40 88 16 59 64 Fax: +49 40 88 16 59 65 Mail: ludger@akampion.com
