Xalud’s lead product, XT-101, treats pain in a manner that is fundamentally different from drugs currently on the market or in development. Rather than attempting to directly block pain signaling, XT-101 treats the inflammation that is responsible for the persistent, amplified pain signaling that typifies chronic pain states. A compelling overview of the science underlying Xalud’s approach can be seen in this presentation by Dr. Elliot Krane at the 2011 TED conference.
“The Mystery of Chronic Pain,” by Dr. Elliott Crane (TED 2011)
Xalud’s technology was developed by Dr. Linda Watkins at the University of Colorado, Boulder. It is based on her pioneering insight that the basis for the strength and persistence of neuropathic pain is inflammation caused by activated glial cells. Neuropathic pain begins when an injury or other stimulus causes pain signals to be transmitted by the neuronal cells in the central nervous system (CNS). Transmission of these pain signals activates the glial cells that surround the neurons and causes the glial cells to generate oxygen radicals and pro-inflammatory cytokines. These radicals and cytokines then support and amplify continued transmission of pain signals by the neurons.
Normally, this cycle eventually subsides, but in neuropathic pain the cycle continues and is reinforced, resulting in persistent, pathological pain. All approved drugs and most drugs in development attempt to treat neuropathic pain by reducing the signaling activity of the neurons. XT-101 uniquely treats pain by modulating the activity of glial cells and reducing inflammation in the CNS.
By treating inflammation rather than blocking neuronal signaling, XT-101 avoids the side effects such as sedation and dizziness that are associated with all leading prescription pain drugs. Furthermore, XT-101 may be synergistic with opioids and prevent the development of opioid tolerance. Opioids are effective at blocking pain signaling, but they also activate glia cells. In essence they work against themselves by amplifying the same pain signaling they are attempting to block. This counter-productive effect may be responsible for the tolerance (and need for increasing dosages of opioids) often seen in chronic pain patients. By de-activating glia cells, XT-101 should prevent the development of tolerance in patients taking opioids and enable the same degree of pain relief to be obtained with lower dosages.
XT-101’s efficacy is derived from its use of the potent, broad spectrum, anti-inflammatory protein interleukin-10 (IL-10). Existing anti-inflammatory products typically act through one or two pathways. IL-10 acts through multiple pathways including:
- suppressing TNF-α, IL-1β, IL-6 transcription, translation, processing, and release;
- down-regulating cytokine receptors and up-regulating antagonists; and
- inhibiting H2O2 and nitric oxide production.
This broad range of activity enables it to normalize glia cell activity and restore homeostasis. XT-101 uses proprietary variant of IL-10 that has demonstrated increased efficacy and duration of action as compared to wild type IL-10.
Inflammatory Joint Disease
Inflammatory joint diseases, including osteoarthritis and rheumatoid arthritis, are marked by patterns of inflammation, macrophage and glial cell activation, and immune system involvement that are similar to the patterns seen in the neuro-inflammatory diseases that were Xalud’s initial focus. IL-10 based therapies may be effective in treating these diseases.