This invention specifically targets nociceptor neurons for the effective inhibition and treatment of chronic pain without the off-target effects that opioids and other drugs might cause due to their action on neighboring neuron subtypes. This technology could be use in medicine for the treatment of pain in chronic disease conditions such as osteoarthritis, rheumatoid arthritis, muscle spasticity, cancer, etc.
Chronic pain is a debilitating condition that is associated with significant medical, emotional, and economic burdens for which few effective treatments are available. Current chronic pain therapies, such as opioids are mostly ineffective or have major off- target effects, such as addictiveness due to action on other neuronal subtypes. In the brain, nociceptor sensory neurons mediate the detection of harmful/injurious stimuli, and their activation produces chronic pain. Nociceptor neurons are dysregulated in muscle spasticity, which may contribute to overactive sensori-motor reflexes, and also innervate joints affected in osteoarticular conditions in order to mediate pain.
This technology is based on the discovery that pain-sensing nociceptor neurons specifically express high levels of ANTXR2 (also known as CMG2) a receptor for anthrax toxin. No other neuron subtypes express the ANTXR2 receptor. By using the endosomal delivery mechanisms inherent to anthrax toxin, it is possible to introduce molecular cargo into nociceptors neurons resulting in a pain-specific block without side effects. For example, molecular cargoes can be intracellularly acting toxins that inhibit or block cell-signaling pathways in vivo or inhibit or block the release of synaptic neurotransmitters eliminating pain.
- Cell type specific
- Pain block without neurological side effects
- Effective endosomal delivery mechanism to introduce cargo inside nocireceptors