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T he company’s drug candidate for neuropathic pai
n, ACD440, is based on the discoveries of the TRPV1 receptor. TRPV1 has been shown to be up-regulated on neurons, to have reduced stimulation thresholds, and to cause an increased perception of pain. It has also been shown to be up-regulated in the skin of individuals with certain types of neuropathic pain. So, blocking the TRPV1 receptor would therefore be interesting when developing new analgesics (painkillers). “There are currently no TRPV1 antagonists [substances that can temporarily block TRPV1] on the market so ACD440 could be a so-called first-in-class,” says Jönsson. “In addition, we are developing a gel for local treatment of peripheral neuropathic pain in order to both be able to provide a good effect and also to avoid systemic side effects.” Neuropathic pain is primarily a chronic disease caused by dysfunction or an injury to the sensory nervous system. Patients could suffer from diabetic neuropathy, or a consequence of shingles, or nerve injury from an accident or surgery. “Nearly 80% of all patients suffering from neuropathic pain are not satisfied with their current treatment, and there are more than 600 million people living with neuropathic pain,” says Jönsson. “In addition, more than 60% of neuropathic pain patients in the USA have been prescribed opioids, which is problematic and something that healthcare and authorities want to avoid in order to overcome the existing opioid crisis in the country. So there is a great need for more effective and safer treatments.” Using opioids, i.e., substances that act on opioid receptors to produce morphine-like effects, means a significant risk of withdrawal symptoms and dependency. Each year 69,000 people worldwide die of opioid overdose, and 15 million people have an opioid addiction (Parthvi et al., American Journal of Therapeutics, 2019). In December 2020, AlzeCure initiated a phase Ib clinical trial for ACD440 to assess tolerability, safety and early signals of efficacy. “We are planning to initiate our next clinical study, a phase II study, against peripheral neuropathic pain and to actively work towards an out-licensing of the project,” says Martin Jönsson. “Moreover we are seeking to be able to conclude and report results for NeuroRestore ACD856, which has a focus on Alzheimer’s disease, as well as initiating the project’s next clinical study. We are also continuing the development of our second Alzheimer’s project, Alzstatin, as well as our TrkA-NAM project against knee-joint arthritis and other difficult pain conditions. So, I can really say that we are quite busy after completing a successful 2021.” Tackling the diabetes pandemic At Swedish company Pila Pharma, the TRPV1 receptor, or as they call it, the chili-receptor is used as the leading principle for a novel treatment of diabetes. “The Nobel Prize has given me the opportunity to share how important I think and believe TRPV1 is. In addition I have for the first time had a reason to share how grateful I am that Julius made his discovery, published his results and made his TRPV1 knock-out mice model [TRPV1 is inactivated] available to others,” says Dorte X. Gram, CEO and founder of PILA Pharma. While working at Novo Nordisk, before founding Pila Pharma in 2014, Dorte used these knock-out mice and was able to show that, after having a high-fat diet, the mice did not become insulin resistant. These mice had better insulin secretion than normal mice fed the same diet. “This data was part of my patent application on TRPV1 inhibitors as a mode of action to treat diabetes,“Inhibition of the activity of the capsaicin receptor in the treatment of obesity and obesity-related diseases and disorders” which includes diabetes, and later became the platform on which Pila Pharma was built,” she describes. H er company is today developing a TRPV1 antagonist, XEND0501, as a novel type of oral anti-diabetic agent. “Our tablet works through a completely new target within diabetes, TRPV1, which is known to have effect on the experience of pain and inflammation regulation,” says Dorte X. Gram. “I believe that diabetes type 2 is an inflammatory disease and NORDICLIFESCIENCE.ORG 67