Michael Tim-Yun ONG, FRCS | Department of Orthopaedics and Trumatology, The Chinese University of Hong Kong; Mingde CAO, PhD; Yuchen LIU, MD, PhD
Competition Sponsor: Research Grants Council of the Hong Kong Special Administrative Region, China
Award Year: 2024
Osteoarthritis (OA), the most common form of arthritis, is characterized by the progressive degradation of joint cartilage, leading to pain, stiffness, and reduced mobility. Pain is the primary symptom of OA, prompting individuals to seek medical assistance as it affects their daily activities, emotional well-being, and overall functionality. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first-line treatment for OA symptom relief. However, long-term use of NSAIDs is often limited by gastrointestinal side effects and insufficient analgesic efficacy. Nav1.8, a sodium channel, has been implicated in the transmission of mechanical pain in a rodent model of OA, suggesting that targeting Nav1.8 on joint nociceptors may offer therapeutic potential for OA pain management. Small-molecule drugs targeting the NaV family have been unsuccessful due to side effects from a lack of targeting specificity and limited bioavailability through systemic administration. We hypothesize that an alternative approach involving the epigenetic modulation of NaV1.8 expression using CRISPR-dCas9 could engineer highly specific, long-lasting, and reversible treatments for OA pain. We anticipate that this study will facilitate the development of a novel therapeutic that can safely and effectively provide sustained relief of OA symptoms.