Migraine is one of the most common medical problems in the U.S. Every year, almost half a billion patients receive acute migraine treatments. Scientists estimate that about 20% to 30% of these patients fail to respond to the triptan class drug treatments. TRV250 is a potential first-in-class molecule to effectively treat acute migraine. This medicine is part of a pipeline of G protein-coupled receptor-targeting drugs.

TRV250 Overview

TRV250 is a medical development from Trevena. Trevena is a biopharmaceutical company that focuses on the development and commercialization of molecules targeting Central Nervous System medical conditions such as migraine, chronic pain, opioid use disorder and severe acute pain. Their innovative approach to pharmaceutical research and drug discovery establishes them as pioneers in acute care medicine.

TRV250 is a small molecule, a G protein-biased ligand. The development of this molecule is based on preclinical work showing that delta receptor-biased ligands may be significantly more effective than unbiased molecules in the treatment of mood disorders. Trevena scientists put this insight to good use by focusing their initial development efforts on the acute treatment of migraine headaches.

Mechanism Of Action

Unbiased G protein-coupled receptors-targeting molecules turn on or off all effects of a targeted receptor. The consequence is that the patient experiences both the benefits and the adverse reactions of the drug. As opposed to unbiased GPCR-targeting drugs, biased ligand drugs offer only the benefits, without the associated adverse reactions. This signal specificity grants improved therapeutic potential by increasing the numbers of eligible patients.

TRV250 targets the delta-receptor. This means that it may be an effective solution to prevent delta receptor-mediated seizures while still preserving all benefits of the previously discovered delta receptor agonists. The mechanism hypothesis for TRV250 assumes that the molecule acts upon the delta receptor and follows the G protein pathway, thus providing all the subsequent benefits to patients. At the same time, the medicine has nothing to do with the beta-arrestin pathway, therefore eliminating the seizure liability.

This medical development could solve one of the biggest problems of the scientific community at the moment, which is to separate the delta receptor effects, in order to effectively treat pain without increasing the risk for seizures in migraine patients.

Research done on mice show promising results. Studies done on beta-arrestin knockout mice showed a reduction of delta receptor-mediated seizures without any negative impact on the therapeutic effects of the drug. This means TRV250 could be the ideal alternative to triptan class drug treatments in patients who are prone to developing seizures as a side-effect of such treatments.

The initial profile of this medicine led the scientists to focus their research on the effective relief of acute migraine. As no selective delta receptor agonists have been FDA approved so far, this could be a breakthrough discovery, a revolutionary medicine that will change the way doctors treat acute migraine pain.

Potential Benefits To Patients

The main benefit to patients is that they can alleviate their acute migraine pains without the risk of delta receptor-mediated seizures. As delta agonist-induced convulsive activity can severely affect these patients, it goes without saying that a molecule like TRV250 would be a real lifesaver to all of these migraine sufferers.

Also, patients who don’t respond well to classic pain treatments may find relief without exposing themselves to the risk of developing an opioid addiction. As there are many patients who need to cope with the ineffectiveness of current treatments, such a solution would solve one of the biggest medical problems of the modern world. This could be a solution to treat those migraine and acute headache patients who can’t find alleviation from pain using available treatments.