Biopharmaceutical Company Announces Preclinical Data For Chronic Neuropathic Epilepsy
Trevena's Preclinical Findings: TRV045 in Neuropathic Pain and Epilepsy Models.
Disclaimer: This article is for informational purposes only and should not be construed as professional medical advice. The content is based on preclinical data and ongoing research, and its conclusions are subject to further validation through clinical trials. Consult healthcare professionals for any medical concerns or questions.
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Trevena, Inc., a biopharmaceutical company listed on the Nasdaq under the ticker symbol TRVN, has announced compelling preclinical data from two collaborative research efforts aimed at understanding the efficacy of their novel therapeutic candidate, TRV045. These studies focus on chronic neuropathic pain and epilepsy, two complex central nervous system (CNS) disorders that significantly affect patients' quality of life.
Research Collaborations and Objectives
The first set of findings stem from experiments conducted in collaboration with scientists at Virginia Commonwealth University (VCU). These studies were presented at the annual meeting of the American Society for Pharmacology and Experimental Therapeutics in May 2024. The primary objective was to investigate the cellular mechanisms underlying the analgesic effects of TRV045, a novel S1P1 receptor modulator, using a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). The second set of studies involved a separate collaboration with the National Institutes of Health (NIH)-supported Epilepsy Therapy Screening Program (ETSP). This research explored the potential effects of TRV045 on acute seizure protection and its capacity to alter seizure development, or epileptogenesis, across three different preclinical models.
Dr. Dana Selley, PhD, Professor of Pharmacology and Toxicology at VCU, highlighted the importance of the preclinical data, emphasizing that TRV045 exhibited consistent and sustained analgesic properties in animal models of neuropathic pain without showing peripheral lymphopenia. Unlike other S1P modulators such as fingolimod, TRV045 did not lead to desensitization of receptor function or downregulation of receptor protein within CNS pain processing centers.
The study revealed that TRV045 operates through agonist signaling at the S1P1 receptor, maintaining its functionality over extended periods. In contrast, fingolimod, an approved S1PR modulator, demonstrated both receptor functional desensitization and protein reduction under similar conditions. This suggests that TRV045 may offer a long-term therapeutic benefit for neuropathic pain without the drawbacks associated with receptor desensitization and protein downregulation.
Mechanistic Insights and Data Presentation
The detailed findings were presented as a poster during the recent pharmacology meeting. The study carefully analyzed whether TRV045 caused S1P1 receptor functional desensitization or protein reduction, even with repeated doses over 14 days. The results were compared to those of fingolimod, which showed substantial receptor desensitization and protein reduction. To measure receptor functional desensitization, the research team used S1P1 receptor-stimulated [35S]GTPγS binding assays in spinal cord membrane homogenates prepared from drug-treated mice. Repeated fingolimod administration (1 mg/kg once daily for 14 days) led to a 70% decrease in [35S]GTPγS binding compared to vehicle-treated controls. In contrast, TRV045 administered orally at 10 mg/kg once daily for the same period did not affect [35S]GTPγS binding.
Additionally, Western immunoblotting was employed to assess S1P1 receptor protein expression in the spinal cord. Fingolimod treatment resulted in a 30% reduction in S1P1 receptor protein levels, whereas TRV045 treatment had no impact. These findings indicate that TRV045 retains receptor functionality and protein expression, potentially offering a more sustainable therapeutic option for patients suffering from neuropathic pain. The second study focused on TRV045's potential anti-seizure effects, conducted in partnership with the NIH’s Epilepsy Therapy Screening Program. The goal was to evaluate TRV045's efficacy in providing acute seizure protection and its ability to influence the course of seizure development, known as epileptogenesis, in various preclinical models.
The data from these models suggested that TRV045 demonstrates statistically meaningful anti-seizure activity. It effectively reduced the incidence and severity of seizures in multiple experimental settings, presenting a strong case for its potential use as a novel anti-epileptic therapy. Additionally, the ability of TRV045 to modify the development of seizures suggests it could play a role in altering disease progression in epilepsy, a feature that distinguishes it from many current treatments that primarily target symptom management.
Potential Clinical Implications
If these preclinical results translate successfully into human studies, TRV045 could offer a new avenue for treating chronic neuropathic pain and epilepsy. Its unique mechanism, which avoids receptor desensitization and protein reduction, might result in fewer side effects and improved long-term outcomes for patients. Chronic neuropathic pain, often resulting from chemotherapy, diabetes, or other conditions, can be challenging to manage with existing therapies, which frequently lose effectiveness over time due to receptor desensitization.
In epilepsy, the ability to provide acute seizure protection and modify the progression of the disorder could significantly impact patient care. Current anti-epileptic drugs (AEDs) often come with limitations, including adverse side effects and the inability to alter the disease's natural course. TRV045's novel mechanism offers hope for a more effective and sustainable treatment option. Trevena plans to further explore TRV045's therapeutic potential through clinical trials. These studies will be crucial for validating the preclinical findings and determining the safety and efficacy of TRV045 in humans. Given the promising preclinical data, there is anticipation within the scientific and medical communities regarding its potential to address unmet needs in CNS disorders.
Trevena's commitment to developing novel CNS therapies underscores the broader effort within the pharmaceutical industry to advance treatments that offer better outcomes for patients with challenging conditions. As research progresses, stakeholders including researchers, clinicians, and patients will be keenly observing the developments related to TRV045 and its potential to transform the treatment landscape for neuropathic pain and epilepsy.
Disclaimer: This article is based on preclinical data and ongoing research. It is intended for informational purposes and should not replace professional medical advice. For any health-related concerns, always consult a qualified healthcare provider.
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