Date: 2013-10-03
Type of
information: Results
phase: preclinical
Announcement: results
Company: Addex Therapeutics (Switzerland)
Product: ADX71441
Action
mechanism:
Disease: anxiety, pain, overactive bladder, alcohol addiction, Charcot-Marie-Tooth 1A disease
Therapeutic
area: CNS diseases - Rare diseases - Neurodegenerative diseases
Country:
Trial
details:
Latest
news:
- • On October 3, 2013, Addex Therapeutics, a company pioneering allosteric modulation-based drug discovery and development announced 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."
- • On May 21, 2013, Addex Therapeutics has announced that its gamma-aminobutyric acid B (GABA-B) receptor positive allosteric modulator, ADX71441, caused dose dependent changes in growth hormone (GH) plasma concentrations compared to vehicle control in a rodent preclinical model. These data are consistent with published scientific literature demonstrating that GABA, the endogenous neurotransmitter for GABA-B receptors, plays both a stimulatory and inhibitory role in modulating the neuro-endocrine regulation of GH secretion in both animals and humans. GH plasma concentration changes occurred at doses and plasma concentrations of ADX71441 which have been demonstrated to induce pharmacological and efficacious effects in preclinical models of CMT1A, anxiety, pain, overactive bladder and alcohol addiction. "The data obtained with ADX71441 demonstrate that growth hormone can be used as a potential biomarker for an efficacy signal and fully supports its inclusion in our first-in-man program," stated Graham Dixon, Ph.D., CSO at Addex. "The use of growth hormone as a biomarker in the Phase 1 will allow us to obtain early information about target engagement, guide dose selection for further clinical development and possibly provide us an understanding of the therapeutic potential of ADX71441."
-
The study was performed on samples from single oral treatment studies where ADX71441 was given at doses of 5, 20 and 80 mg/kg. Assessment of GH and ADX71441 plasma concentrations were performed at 4 and 24 hours post-treatment. The results demonstrate a direct relationship between plasma concentrations of ADX71441 and effect on GH levels.
Is
general: Yes
