Development of a Novel, Nonaddictive Analgesic for Postsurgical Pain
Abstract
Rationale: Opioid medications such as morphine, hydrocodone, and oxycodone are considered the most effective painkillers available. However, these medications come with serious side effects, including high addictive potential. This has led to a widespread opioid epidemic across the nation. With high rates of chronic pain, post-traumatic stress disorder, and other risk factors for opioid use, Veterans are especially vulnerable to addiction and overdose, which is estimated at double the general population. These risk factors are compounded and amplified by surgical procedures, where opioids are commonly prescribed post-operatively. Continued exposure of Veterans to opioids in a surgical setting, against the backdrop of these converging risk factors, results in much higher rates of long-term opioid use and addiction, even after relatively low-risk surgeries. The need to reduce the use of opioids in surgical settings is thus critical. We believe the best solution to arrest the cycle of chronic pain and opioid abuse is by developing a painkiller that is potent but lacks the addictive side effects. Objectives: Blue Therapeutics is developing a new type of small molecule painkiller called NNTA. This molecule specifically targets a recently discovered receptor in the central nervous system. Because of its target, NNTA produces excellent analgesia (50X that of morphine) but does not show reward behavior or physical dependence. We are currently advancing NNTA through toxicology and safety studies through the support of the National Institute on Drug Abuse. The objective of this proposal is to test this molecule in a setting that would be relevant for Veterans undergoing common surgical procedures. This will include testing the molecule in a standard rodent model of post-operative pain, investigating the abuse liability potential of this molecule when it is made freely available, and determining its relevance for human use by showing that the target is present in human spinal cord tissue. Focus Area: Rehabilitation: Post-Operative Pain Management. This proposal directly addresses the focus area by testing a novel, non-addictive analgesic in a post-operative pain setting suitable for Veterans. Impact: If successful, this project would lead to a viable alternative to opioid painkillers for post-operative pain. Given the frequency of surgeries such as total hip or knee replacement, this would displace a large quantity of opioids from the Veteran and civilian populations and cut down on a key risk amplifier for long-term opioid use and dependence. Thus, the potential impact of this proposal is the ability to more effectively treat pain, reduce opioid prescriptions, and blunt the cycle of opioid addiction and death. Clinical Applications: The initial clinical indication will be for post-operative pain. This application will be for short-term (less than one week) use. The treatment would be useful for common musculoskeletal surgical procedures that include total hip or total knee replacement, pain due to severe battlefield injuries, or other general uses for moderate to severe pain. Ultimately, if NNTA retains its potency in human use while lacking abuse potential, it would have a broad range of clinical applications for the treatment of pain wherever standard opioids are currently used. Timeline: The timeline for this project is 1.5 years. We expect to file for Investigational New Drug (IND) status with the FDA, enabling us to begin human clinical trials, within 2 years. The initial indication will be for post-operative pain. This accelerated timeline is due in part to the fact that IND-studies are ongoing with support from the National Institutes of Health. Military Relevance/Community: Orthopedic injuries are the most common medical complaint of military personnel and account for 50% of disease and non-battle related injuries (Cowen, et al., 2003; Belmont, et al. 2010). These injuries are typical
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710548
Entities
People
- Ajay Yekkirala
Organizations
- Blue Therapeutics (United States)
- United States Army