Addex ADX71441 Dose Dependently Reduced PMP22 Expression Comparable to Baclofen in a Pre-Clinical Transgenic Model of Charcot-Marie-Tooth 1A Disease
(Thomson Reuters ONE) -
Addex Therapeutics /
Addex ADX71441 Dose Dependently Reduced PMP22 Expression Comparable to Baclofen
in a Pre-Clinical Transgenic Model of Charcot-Marie-Tooth 1A Disease
. Processed and transmitted by Thomson Reuters ONE.
The issuer is solely responsible for the content of this announcement.
Geneva, Switzerland, 3 October 2013 - Addex Therapeutics (SIX: ADXN), a leading
company pioneering allosteric modulation-based drug discovery and development
announced today that ADX71441 dose dependently reduced PMP22 expression
comparable to baclofen in a preclinical transgenic model of Charcot-Marie-Tooth
1A disease (CMT1A).
ADX71441 was studied in the transgenic CMT1A rat model which displays a 1.6-fold
PMP22 overexpression (mRNA level) and exhibits clinical abnormalities, such as
reduced nerve conduction velocity and lower grip strength that closely mimic
findings in CMT1A patients. In a 5 day comparative study with baclofen, a dose-
response was successfully established for orally administered ADX71441. ADX71441
given orally once daily significantly reduced PMP22 mRNA expression at 3 mg/kg
and 6 mg/kg (0.98-fold±0.49 and 0.93-fold±0.35, respectively). Baclofen given
orally twice daily reduced PMP22 mRNA expression at 3mg/kg (0.91-fold±0.25).
ADX71441 did not significantly reduced PMP22 mRNA expression at 1mg/kg (1.48-
fold±0.26) compared to CMT vehicle group (1.6-fold±0.19).
"These findings in the CMT1A transgenic rat model which show that ADX71441 has
comparable efficacy to Baclofen are very promising," Professor Michael Sereda,
of the Max-Planck Institute of Experimental Medicine, Göttingen, Germany, in
whose laboratories the study was performed. "These results are consistent with
previous reported data which suggest that intraperitoneal application of
ADX71441 could lower toxic PMP22 overexpression and potentially delay the
progression of the disease. Oral application of ADX71441 may therefore offer a
unique therapeutic opportunity for CMT1A patients."
About Charcot Marie Tooth Disease Type 1A (CMT1A)
CMT1A is a rare (1:5,000) hereditary motor and sensory demyelinating peripheral
neuropathy (also known as Hereditary Motor and Sensory Neuropathy, HMSN) which
is caused by an intrachromosomal duplication and consecutive toxic
overexpression of the PMP22 gene on chromosome 17. CMT1A is one of the most
common inherited peripheral nerve-related disorders which is passed down through
families in an autosomal dominant fashion. CMT1A disease becomes evident in
young adulthood and slowly progresses with distally pronounced muscle weakness
and numbness. Pain can range from mild to severe. The disease can be highly
debilitating with wheel chair-boundness and is often accompanied by severe cases
of neurological pain. There is no known cure for this incapacitating disease.
About GABA-B Activation and ADX71441
Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C
class of GPCR, is clinically & commercially validated. Generic GABA-B receptor
agonist, baclofen, is marketed for spasticity and some spinal cord injuries, and
used for OAB, but is not commonly used due to severe side effects of the drug
and rapid clearance. ADX71441 is a potent selective positive allosteric
modulator (PAM) which potentiates GABA responses at the GABA-B receptor.
ADX71441 is a novel, first-in-class, oral, small molecules that has demonstrated
excellent preclinical efficacy and tolerability in several rodent models of
pain, anxiety, addiction and overactive bladder (OAB) and have also proven
efficacy in a genetic model of Charcot-Marie-Tooth Type 1A disease (CMT1A).
ADX71441 differs from the generic drug baclofen in that it is a positive
allosteric modulator rather than an orthosteric agonist at the GABA-B receptor.
ADX71441 only acts when the natural ligand (GABA) activates the receptor, and
therefore respecting the physiological cycle of activation. It has been proposed
that PAMs produce less adverse effects and lead to less tolerance than direct
agonists (May and Christopoulos 2003; Langmead and Christopoulos 2006; Perdona
et al. 2011; Urwyler 2011; Gjoni et al., 2008; Ahnaou et al).
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a development stage company
focused on advancing innovative oral small molecules against rare diseases
utilizing its pioneering allosteric modulation-based drug discovery platform.
The Company's two lead products are being investigated in Phase 2 clinical
testing: dipraglurant (an mGlu5 negative allosteric modulator or NAM) is being
developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-
LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric
modulator or PAM) is being developed in collaboration with Janssen
Pharmaceuticals, Inc., to treat both schizophrenia and anxiety as seen in
patients suffering from major depressive disorder. Addex also has several
preclinical programs including: GABA-B positive allosteric modulator (PAM) for
Charcot-Marie-Tooth (Type 1a) disease, spasticity in patients with multiple
sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4 PAM for
MS, Parkinson's disease, anxiety and other diseases. Allosteric modulators are
an emerging class of small molecule drugs which have the potential to be more
specific and confer significant therapeutic advantages over conventional
"orthosteric" small molecule or biological drugs. The Company uses its
proprietary discovery platform to target receptors and other proteins that are
recognized as essential for the therapeutic modulation of important diseases
with unmet medical needs.
Tim Dyer
Chief Executive Officer
Addex Therapeutics
+41 22 884 1561
PR(at)addextherapeutics.com
Disclaimer: The foregoing release may contain forward-looking statements that
can be identified by terminology such as "seek", "not pursue", "not approvable",
"continue", "believes", "believe", "will", "remained open to exploring",
"would", "could", or similar expressions, or by express or implied discussions
regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its
business, the potential approval of its products by regulatory authorities, or
regarding potential future revenues from such products. Such forward-looking
statements reflect the current views of Addex Therapeutics regarding future
events, future economic performance or prospects, and, by their very nature,
involve inherent risks and uncertainties, both general and specific, whether
known or unknown, or any other factor that may materially differ from the plans,
objectives, expectations, estimates and intentions expressed or implied in such
forward-looking statements. Such factors may in particular cause actual results
with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-B or other therapeutic
targets to be materially different from any future results, performance or
achievements expressed or implied by such statements. There can be no guarantee
that Addex Therapeutics will complete the restructuring and reduction of its
liabilities or any financing nor that allosteric modulators of mGlu2, mGlu4,
mGlu5, GABA-B or other therapeutics targets will be approved for sale in any
market or by any regulatory authority. Nor can there be any guarantee that
allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-B or other therapeutic
targets will achieve any particular levels of revenue (if any) in the future. In
particular, management's expectations regarding allosteric modulators of mGlu2,
mGlu4, mGlu5, GABA-B or other therapeutic targets could be affected by, among
other things, unexpected actions by our partners, unexpected regulatory actions
or delays or government regulation generally; unexpected clinical trial results,
including unexpected new clinical data and unexpected additional analysis of
existing clinical data; competition in general; government, industry and general
public pricing pressures; the company's ability to obtain or maintain patent or
other proprietary intellectual property protection. Should one or more of these
risks or uncertainties materialize, or should underlying assumptions prove
incorrect, actual results may vary materially from those anticipated, believed,
estimated or expected. Addex Therapeutics is providing the information in this
press release as of this date and does not undertake any obligation to update
any forward-looking statements contained in this press release as a result of
new information, future events or otherwise, except as may be required by
applicable laws.
This announcement is distributed by Thomson Reuters on behalf of
Thomson Reuters clients. The owner of this announcement warrants that:
(i) the releases contained herein are protected by copyright and
other applicable laws; and
(ii) they are solely responsible for the content, accuracy and
originality of the information contained therein.
Source: Addex Therapeutics via Thomson Reuters ONE
[HUG#1733348]
Unternehmensinformation / Kurzprofil:
Datum: 03.10.2013 - 07:00 Uhr
Sprache: Deutsch
News-ID 302438
Anzahl Zeichen: 10161
contact information:
Town:
Plan-les-Ouates, Geneva
Kategorie:
Business News
Diese Pressemitteilung wurde bisher 206 mal aufgerufen.
Die Pressemitteilung mit dem Titel:
"Addex ADX71441 Dose Dependently Reduced PMP22 Expression Comparable to Baclofen in a Pre-Clinical Transgenic Model of Charcot-Marie-Tooth 1A Disease"
steht unter der journalistisch-redaktionellen Verantwortung von
Addex Therapeutics (Nachricht senden)
Beachten Sie bitte die weiteren Informationen zum Haftungsauschluß (gemäß TMG - TeleMedianGesetz) und dem Datenschutz (gemäß der DSGVO).
