Theralase Technologies Inc. has announced a significant breakthrough in cancer research with the discovery of a new mechanism of action for its lead drug Ruvidar™. Preclinical studies have demonstrated that Ruvidar effectively inhibits DeUbiquitinating Enzymes (DUBs), a class of enzymes linked to numerous cancers and neurodegenerative diseases.
The Toronto-based clinical stage pharmaceutical company revealed that Ruvidar's ability to inhibit DUBs represents a promising new approach in overcoming drug resistance in cancer treatment. DUBs play a critical role in cellular processes by removing ubiquitin molecules from target proteins, which can lead to cellular damage when dysregulated.
Understanding the Mechanism of Action
Ubiquitin, a small protein found in all eukaryotic cells, regulates various cellular processes including gene expression, DNA repair, cell metabolism, and cell death. It functions primarily through ubiquitination, a process where ubiquitin attaches to target proteins, marking them for degradation or altering their activity.
Altered DUBs activity has been associated with multiple pathologies, particularly cancer. Recent research suggests that dysregulation of DUBs plays a significant role in the development of drug resistance, enabling cancer cells to escape cell death when exposed to anti-cancer drugs.
The company's latest research demonstrates that Ruvidar inhibits DUBs activity in a dose-dependent manner. Laboratory tests showed that increasing concentrations of Ruvidar directly correlate with reduced DUBs activity, with 100 μM of Ruvidar resulting in almost complete inhibition of DUBs activity.
"Our latest research provides compelling evidence that Ruvidar not only induces oxidative stress through the production of Reactive Oxygen Species to destroy cancer cells, but also directly inhibits DUBs activity—a key host mechanism exploited by the cancer cell to evade immune defenses," said Dr. Mark Roufaiel, Research Scientist at Theralase.
Dual Mechanism Enhances Therapeutic Potential
This newly discovered mechanism adds to Ruvidar's previously known ability to induce oxidative stress in cells through the production of Reactive Oxygen Species (ROS). The combination of these two mechanisms—DUBs inhibition and ROS production—creates a powerful approach to cancer cell destruction.
The dual mechanism positions Ruvidar as a promising therapeutic candidate, particularly against cancers where traditional chemotherapeutics show limited effectiveness. According to company researchers, this approach could be especially valuable in addressing the growing challenge of chemotherapy and radiation resistance in cancer treatment.
Dr. Arkady Mandel, Chief Scientific Officer at Theralase, emphasized the broader implications of this discovery: "With the increasing prevalence of chemoradiotherapy resistant cancers, Ruvidar, as an effective DUBs inhibitor, may be indispensable clinically to be used as a combinational therapy with various chemotherapy drugs and/or radiotherapy."
Potential Applications Beyond Cancer
While the primary focus remains on cancer treatment, Theralase executives suggest that Ruvidar's effectiveness against DUBs could potentially extend to other medical conditions. These include age-associated conditions, neurodegenerative diseases such as Alzheimer's, Parkinson's, and Multiple Sclerosis, as well as various infectious diseases.
"The discovery of Ruvidar's effectiveness against DUBs is a notable milestone in the development of Theralase's small molecule program," added Dr. Mandel.
Clinical Development Pipeline
Theralase is currently pursuing clinical development of Ruvidar for numerous cancers, including brain and lung cancer. Roger DuMoulin-White, President and Chief Executive Officer of Theralase, expressed optimism about the drug's potential.
"According to recent peer-reviewed research, reducing DUBs plays a very important role in the war against cancer and its innate ability to build up drug resistance," said DuMoulin-White. "This latest research reinforces an additional mechanism of action beyond direct cancer destruction and indirect immune stimulation, stripping away one of cancer's final defense mechanisms."
Market and Development Outlook
Theralase Technologies Inc. (TSXV: TLT) (OTCQB: TLTFF) is focused on the research and development of light, radiation, sound and/or drug-activated small molecules and their formulations. The company's primary objective is efficacy in the destruction of various cancers, bacteria, and viruses, with safety as a secondary objective.
As with many pharmaceutical developments, the company notes that there are risks and uncertainties associated with the clinical development process. These include securing regulatory approvals, completing clinical studies in a timely fashion, and successfully commercializing the drug formulations.
The company plans to report on the clinical safety and efficacy of Ruvidar as development progresses through various cancer indications, potentially opening new avenues for treatment in areas of significant unmet medical need.
