AHLi-11 is an siRNA drug that temporarily inhibits the expression of human p53 and is in development for hearing loss, initially induced by acoustic trauma or ototoxic drugs. Hearing loss is a major problem in the US and across the globe. It is an under-diagnosed and under-treated health issue. Often, extensive damage is done to the auditory system before it is noticed. The majority of hearing loss appears to be due to overexposure to environmental noise, often in the workplace. An estimated 28 million Americans have some degree of hearing loss. The most frequent reasons for acute hearing loss are acoustic trauma or patients’ treatment with ototoxic drugs, aminoglycoside antibiotics (gentamycin and others) or cancer therapeutics such as cisplatin. In all these conditions, similar molecular mechanisms, most likely associated with p53 dependent stress response, are suspected of triggering cochlear hair cell apoptosis. Both gentamycin and cisplatin display specific toxicity not only towards inner ear hairy cells but also nephrotoxicity, indicating that potential common pathways are involved. Indeed, inhibition of p53 with small molecule was protective against cisplatin-induced apoptosis of both kidney tubular cells and cochlear hair cells. Furthermore, it was also protective against ischemia/reperfusion-induced proximal tubule injury leading to acute renal failure, supporting involvement of common cytotoxicity mechanisms for cisplatin and ischemia-reperfusion.
AHLi-11 is scheduled for IND submission in 2009.