Development of NaV1.7 Activity-Blocking Antibody for Analgesia
Abstract
Adequate treatment of pain represents a dire unmet need in modern medicine both in civilian and military medicine. Opioids are used as current standard treatment for both acute and chronic pain conditions, but their use is problematic due to severe side effects that include constipation and potentially fatal respiratory depression. Additional problems with opioid usage include tolerance, withdrawal symptoms, and frequent subsequent dependence leading to opioid abuse and what has been called an "opioid epidemic." To address this unmet medical need, we propose developing an antibody-based therapeutic that inhibits the function of the human sodium channel NaV1.7. NaV1.7 has a central role in human pain perception as evidenced by the fact that rare human subjects who lack this channel are unable to sense any pain. NaV1.7 is expressed in the neurons of the peripheral nervous system where it is required for transmission of pain signals to the brain. Thus, a therapeutic that blocks NaV1.7 temporarily is expected to interfere with pain perception and provide significant pain relief. Antibodies are a class of protein-based therapeutics that have demonstrated a high degree of clinical usefulness against a number of human maladies, such as cancer. The utilization of an antibody targeting approach against NaV1.7 has a number of advantages over other pain relief approaches, such as the elimination of addictive potential, high selectivity for NaV1.7 eliminating off-target toxicities, and improved half-life thereby decreasing dosing frequency. A potent NaV1.7 blocking antibody would be the first of a new class of urgently needed pain medications that has the potential to drastically reduce current use of opioids.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710054
Entities
People
- Lee Swem
Organizations
- Achaogen (United States)
- United States Army