|
Quark’s current AHL drug candidate is a siRNA using proprietary novel structure and is administered non-invasively into the inner ear. Advanced preclinical studies are ongoing for acute hearing loss indications such as ototoxicity- and acoustic trauma-induced hearing loss.
We have previously shown effectiveness of the siRNA approach to treat hearing loss. Specifically an siRNA temporarily inhibiting p53 (previous candidate AHLi-11) applied to the round window membrane of inner earsrescued cochlear hair cells from carboplatin-induced apoptosis in a chinchilla model. In the chinchilla study, AHLi-11 also protected cochlear hair cells from acoustic trauma induced apoptosis and attenuated hearing loss. Pharmacodynamic effect transtympanic of siRNA was also shown in non-human primates following transtympanic delivery. However, since clinical applicability of transtympanic siRNA administration was proven to be problematic, for further clinical development non-invasive siRNA administration using eardrops was developed. siRNA delivered by ear drops was shown to inhibit target gene expression in rat cochlea. Imaging studies have confirmed that eardrop siRNA can be also effectively delivered to the inner cells in non-human primates. The drug candidate is in preclinical studies in otoprotective indications (i.e., acoustic trauma and drug-induced ototoxicity). In addition, we have started programs aimed at promoting hearing cell regeneration.
Hearing loss is a major problem in the US and across the globe. It is an under-diagnosed and under-treated health issue. An estimated 28 million Americans have some degree of hearing loss resulting in a significant negative impact on the quality of life. Both genetic and environmental causes can lead to hearing loss. Damage to the inner ear (cochlea) or to the nerve cells pathways from the inner ear to the brain sensorineural results in hearing loss that cannot be medically or surgically corrected. Hearing loss such as noise induced and age induced hearing loss, are permanent due to the lack of spontaneous regeneration in the sensory hearing cells. Acute sensorineural hearing loss is caused most often by acoustic trauma or patients’ treatment with ototoxic drugs, including aminoglycoside antibiotics (gentamycin and others) or cancer therapeutics such as cisplatin. In all these conditions, a similar molecular mechanism is suspected of triggering cochlear hair cell apoptosis.
|