Date: 2017-03-01
Type of
information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the Association for Research in Otolaryngology Conference (ARO)
Company: Strekin (Switzerland)
Product: STR001 (pioglitazone)
Action
mechanism: PPAR agonist. The active principle of STR001 is pioglitazone. In preclinical studies, STR001 provided significant protection of auditory hair cells of the inner ear in models of hearing loss. Hair cells are responsible for converting airborne sound to electrical signals to the brain and are commonly lost or dysfunctional in many types of hearing loss. Strekin has obtained exclusive worldwide rights to a patent covering the use and route of administration of STR001 as a treatment for hearing loss.
Disease: hearing loss, preservation of residual hearing in patients undergoing cochlear implantation surgery
Therapeutic
area: Otorhinolaryngology
Country:
Trial
details:
Latest
news:
- • On March 1, 2017, Strekin announced the presentation of new preclinical dat on STR001 at the Association for Research in Otolaryngology Conference (ARO), Baltimore, USA. In a poster presentation (#PS792) entitled "Peroxisome proliferator activated receptor-gamma and alpha agonists protect auditory hair cells from gentamicin?induced oxidative stress and apoptosis”, researchers observed that the PPAR agonist pioglitazone, the active ingredient in STR001, was highly effective in preventing damage to the sensory hair cells of the inner ear. The research was led by Daniel Bodmer, MD, PhD, and Chairman of the Department of Otolaryngology Head & Neck Surgery at the University Hospital of Basel. Dr. Bodmer’s analysis was performed in a model in hearing research in which the organ of Corti, the structure containing auditory hair and sensory cells, is studied in tissue culture. Treatment of cultures with gentamicin, an antibiotic that often leads to hearing loss in humans, caused destruction of 50% of hair cells which was almost completely prevented by STR001. Further analysis showed that gentamicin induced the production of oxygen free radicals, promoted lipid oxidation, and activated the cell death pathway (apoptosis) in hair cells, all of which were prevented by STR001. In a second presentation (#PS159) entitled “Intra-tympanic Administration of Pioglitazone, a Peroxisome Proliferator-Activated Receptor Gamma Agonist, Protects from Noise-Induced Hearing Loss” Dr. Anna-Rita Fetoni and her colleagues from the Catholic University of Rome, showed that a single intratympanic injection of STR001-IT was highly protective in a rodent model of noise-induced hearing loss. The protection afforded by STR001 was accompanied by a strong reduction in markers of oxidative stress in auditory hair cells and neural elements in the cochlea. This protection was even partially maintained when injecting STR001IT 48 hours after the noise challenge which based on our knowledge was never achieved up to now. These data, together with the data from Dr. Bodmer’s group, suggest that STR001 has the potential to be a new and differentiated therapy for many types of hearing loss through favorable effects on multiple pathways.
- On June 30, 2016, Strekin announced oral and poster presentations of preclinical data on the efficacy and
mechanism of STR001 in the treatment of hearing loss at the Molecular Biology of Hearing and Deafness Conference, Cambridge, UK. The presentation (#S79), was titled "Agonists of the peroxisome proliferator activated receptors-gamma
and -alpha afford significant protection of auditory hair cells from gentamicin-induced ototoxicity". Researchers observed that the PPAR agonist pioglitazone was highly effective in preventing damage to the sensory hair cells of the inner ear. The research was led by Daniel Bodmer, co-founder of Strekin.
Dr. Bodmer’s analysis was based on studies in a model in hearing research in which the organ of Corti, the structure which contains auditory hair and sensory cells, is studied in tissue culture. Treatment of these cultures with gentamicin, a widely used antibiotic that often leads to hearing loss, caused destruction of 50% of the hair cells. STR001 provided significant protection, allowing survival of more than 90% of the hair cells in the presence of this agent. Further analysis showed that gentamicin induced the production of oxygen free radicals leading to oxidative stress, known to cause modification and damage to cellular proteins, lipids, and DNA. STR001 prevented oxygen free radical formation by regulating the expression of proteins in several pathways of the cellular defense from oxidative stress. This is just one of many potential protective mechanisms for STR001, as its cellular receptor has been shown to play additional roles in diverse cellular processes such as metabolism, inflammation, and cell survival.
The medical implications of STR001 are presently investigated in a large Phase 2 clinical trial in patients,testing the effect of the drug to preserve residual hearing in patients receiving a cochlear implant.
Is
general: Yes
