BioLineRx in-licenses new compound to treat neuropathic pain

BL-1110 may also be developed for the treatment of scleroderma, an autoimmune disease characterized by a hardening and tightening of the skin and connective tissues. The compound, which had been previously developed as part of BioLineRx’s Early Development Program under the name EDP-34, was in-licensed from the University of Colorado.

Neuropathic pain is caused by damage or diseases affecting the nervous system, and usually does not respond well to regular painkillers. One of the most potent drugs for the treatment of neuropathic pain is morphine; however, its efficacy is often significantly limited due to the body’s development of tolerance to the drug, as well as its severe side effects.

Morphine can create neuroinflammation in the central nervous system, which has been linked to the suppression of morphine analgesia, as well as the enhancement of morphine-induced tolerance, dependence and reward associated with drug abuse. Recent studies show part of these neuroinflammatory effects are triggered by the interaction of morphine with glial cells, which are highly prevalent in the central nervous system.

BL-1110, which was invented by Prof. Linda R. Watkins from the Psychology and Neuroscience Department, and Prof. Hang Hubert Yin from the Chemistry and Biochemistry Department – both from the University of Colorado at Boulder, blocks the interaction of morphine with glial cells, thereby enhancing the analgesic effect of morphine, and reducing concurrent adverse effects and inflammatory processes.

BL-1110 is a small molecule that targets the critical TLR4/MD-2 complex formation, thus preventing the binding of morphine to the TLR4 receptor in glial cells. BL-1110 is administered orally, together with morphine or other opioids. In preclinical studies in rats, BL-1110 was shown to enhance the effects of morphine.

Furthermore, the studies show the drug penetrates the blood-brain barrier and reaches the central nervous system with high efficiency, that it is safe for use and that it does not induce adverse effects at doses that are much higher than the effective dose.

"BL-1110 works through a novel mechanism-of-action, based on our recent discovery that opioids, such as morphine, cause the activation of glial cells. This glial activation results in the release of pro-inflammatory factors, which suppress the desired opioid-induced neuronal analgesic effect, thereby reducing the efficacy of the opioid. Furthermore, evidence suggests that glial activation contributes to the development of opioid tolerance, dependence and abuse," explained Prof. Hang Hubert Yin.

"We therefore have high hopes that BL-1110 will be a valuable companion to opioid therapies, enhancing their efficacy and reducing their negative side effects."

"Neuropathic pain is a major health problem affecting the quality of life of millions of people around the globe on a daily basis. Despite its widespread occurrence, it is notoriously difficult to treat. Opioids, such as morphine, are a potent option for the treatment of neuropathic pain, but they are generally not used as a first-line treatment due to the considerable risk of adverse side effects, tolerance and dependence.

BL-1110 offers the possibility of mitigating morphine tolerance and side effects while enhancing the analgesic effect. This drug could offer a real breakthrough for the treatment of this challenging and persistent pathology. We are therefore very pleased to in-license this drug and continue its development," said Dr. Kinneret Savitsky, CEO of BioLineRx.