Neuropathic pain is usually accompanied by tissue injury and many a times could be due to damaged nerve fibers which maybe dysfunctional, or injured. These damaged nerve fibers send incorrect signals to other pain centers and the impact of which is a change in nerve function both at the site of injury and areas around the injury.
The treatment of neuropathic pain commonly involves the prescription of opioids, anti-depressants or anti-convulsants, but today analgesics have not progressed far beyond its main active ingredient, morphine, despite severe side effects such as tolerance, addiction and abuse.
Paris-based Pharmaleads, an emerging pharmaceutical company developing innovative products for the management of acute and chronic severe pain, has announced that it has successfully completed Phase I single ascending dose (SAD) trial in France with its oral drug candidate for Neuropathic pain- DENKI candidate PL265.
The mechanism of the drug hinges on its ability to boost the concentration of endogenous agonists that act on the delta opioid receptor, which is a key player in the development and expression of neuropathic pain.
The peptide candidate is proven to be safe and well-tolerated. Pharmacokinetic and pharmacodynamic studies showed that PL265, was slowly transformed in plasma into its active metabolite (PL254). This transformed compound was found to inhibit both of its target enzymes, aminopeptidase N (APN
) and neprilysin (NEP), which are responsible for the physiological degradation of enkephalins. This inhibition was effective for more than 24 hours after single doses of 400 and 800mg of PL265, making it an ideal oral candidate for the treatment of the chronic pain. The biotech will now move its candidate into a Phase I MAD study in the UK and expects to have result data by 2018.“DENKIs don’t cross the blood-brain barrier, and they don’t lead to physical dependence or show abuse potential. Results from this study show that PL265, via its active metabolite PL254, is able to inhibit its two key targets and provide strong evidence supporting our hypothesis that DENKIs are the only drug candidates in development that harbor the analgesic properties of opiates without their side-effects,” says Michel Wurm, Director of Corporate Development.
PL265 is also a promising candidate for local administration such as eye-drops, for which the Pharma is currently completing evaluation for the treatment of ocular pain and dry eye syndrome in animal models.
