Spider approach: arthropod venom helped create a promising painkiller
An analgesic based on substances derived from crab spider venom has passed a full range of preclinical tests in the Russian Federation. It will be effective for people with neuropathic pain and can improve the condition of osteoarthritis, cystitis, trigeminal neuralgia and migraines, as well as chronic cough. Clinical trials may begin as early as 2025, and the expected market launch date is 2029, the developers told Izvestia. Experts note the prospects for the creation of new painkillers, but emphasize that it is necessary to wait for the results of all studies.
A cure for spider venom
A Russian company has completed preclinical trials of an innovative painkiller based on a substance derived from the venom of the spider Thomisus onustus. It is a crab spider that is found in Europe, North Africa, as well as parts of the Middle East and Asia.
The new drug was named Purotoxin-6. The estimated market launch date is 2029, with potential coverage of more than 8 million patients with neuropathic pain, the developers said. The principle of action of the substance is to inhibit special pain receptors (P2X3). They play a key role in causing pain in conditions such as osteoarthritis, cystitis, trigeminal neuralgia and migraines, as well as in chronic coughing.
According to the developers, currently there is only one drug that affects P2X3 receptors, which is registered in the EU, Switzerland and Japan. However, this drug has a side effect, which is expressed in a disorder of taste sensations (dysgeusia).
— Natural poisons are unique combinatorial libraries of pharmacologically active substances targeting neuroreceptors. They resemble the artificial libraries that pharmaceutical companies use when searching for new drugs. Our peptide exhibits exceptional selectivity for P2X3 receptors and acts effectively on them," said Alexander Vasilevsky, founder of the Skolkovo resident company Analgesics of the Future, head of the laboratory at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, head of research.
The effectiveness of the drug has been tested in numerous trials — on isolated sensory neurons in the laboratory, on recombinant receptors, as well as using genetically modified, or knockout, mice.
— It is very important that FA006 does not cause dysgeusia (a form of taste disorder. — Izvestia), which means it can serve as a unique class of analgesics without side effects, — said Alexander Vasilevsky.
T. onustus spiders live in the flowers of lowland vegetation. Females are larger in size and are able to vary their color, choosing from white, yellow and pink, which is most suitable for the pigment of the flower. This mimicry of color allows them to hide from predators and increases their chances of insect prey. Males are smaller than females and have a dull color, usually green or brown.
In what form will the medicine be released?
In addition to selectivity, Purotoxin-6 demonstrates other properties, such as the duration of effect in animal experiments and stability, for example, in blood plasma, which is unusual for most peptide compounds. Its use may turn out to be more effective, convenient and safe than using the existing arsenal of medicines for pain syndromes, said Dmitry Poteryaev, CEO of the development company.
The resulting product is a solution for subcutaneous injection, available as a pen for multiple dosing.
— The development of innovative technologies in medicine plays a key role in transforming treatment approaches and improving the quality of life of patients. In particular, the development of a new class of analgesics will improve the effectiveness of treatment, while minimizing side effects. On the part of the foundation, we are ready to provide comprehensive support in the development of our projects and the Russian pharmaceutical industry as a whole," Alexey Pleskov, director of the Center for Technology Development in Biology, Medicine and Agriculture at the Skolkovo Foundation, told Izvestia.
According to Rustem Gayfutdinov, associate professor of the Department of Neurology and Neurosurgery at Kazan State Medical University, the search for alternatives to traditional painkillers is extremely relevant now, since existing drugs, although they have an effect, have a side effect that negatively affects patients with concomitant diseases.
— Traditional pain medications can provoke hypertensive crises or gastric ulcer, so it is necessary to search for new treatment approaches that, on the one hand, relieve pain and, on the other, do not cause complications. And they can be borrowed from the animal kingdom. This is a justified path for science. We need to try and conduct a wide range of experimental studies," said Rustem Gayfutdinov.
The development of a new analgesic looks interesting and promising, but in order to talk about the features of the new drug, it is necessary to wait for the results of a full range of clinical trials, Mikhail Bolkov, a researcher at the Institute for the Study of Aging at the Russian State Scientific and Clinical Center of the Pirogov Russian National Research Medical University, told Izvestia.
The results of a full range of preclinical studies are published in the journal Molecular Therapy. The company plans to start clinical trials in 2025. If they are successful, an analgesic agent will appear on the market that does not exhibit undesirable side effects, as well as a structure and mechanism of action that differs from all existing ones.
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