Challenges...
Many common diseases still lack effective and/or curative treatments, and sometimes the only option is to “manage” the condition. It is also common that many patients use many treatments to manage a condition to improve the quality of life, even if the treatment is not clinically-proven.
Our group undertakes challenges that are outside the box, employ outside the box thinking, many times very risky, and employ our expertise bringing together the disease and innovative solutions grounded in medicinal chemistry to improve the quality of life for the patients. More importantly, we know that it cannot be achieved without extensive collaboration with experts, and we cherish our extensive collaborative network in advancing the solutions to the clinic.
One such condition is neurodegeneration, due to multiple sclerosis (MS) or neuropathy. In MS, the immune system attacks the central nervous system, progressively disabling the patient. Neuropathy – caused by diabetes, chemotherapy or another condition – reduces sensation in the limbs, affecting a patient’s quality of life. Current treatments may slow disease progression and manage symptoms, but repairing the neuronal damage would reverse and potentially cure these conditions.
The Multi-Organ Transplant Clinic at University Health Network (UHN) undertakes the highest number of transplants in North America, and the Kotra group works closely with the clinicians tackling important transplant-related health challenges, including infections such as cytomegalovirus (CMV), hepatosteatosis and non-alcoholic fatty liver disease (NAFLD). Such clinical conditions significantly lower the quality of life for transplant recipients.
Often, a potential treatment may exist, but it’s not fully understood. For example, medical cannabis seems to be effective for certain conditions but lacks scientific evidence about the mechanisms of action, since it has not been studied as rigorously as traditional drugs. In addition, there is a large volume of anecdotal and misinformation about this substance as a medicine.
Active research projects in the group are:
-
Drugs targeting neuroinflammation and neurodegenerative conditions, such as multiple sclerosis, diabetic neuropathy
-
Inhibitors targeting thrombocytopenia (ITP and related blood disorders)
-
Cannabinoids and medical cannabis: chemistry, biology, pharmacology and clinical studies
-
Novel drug delivery platforms and drug formulations
Solutions in Our (Kotra research group) Lifetime...
Under the auspices of Krembil Research Institute, University Health Network and Leslie Dan Faculty of Pharmacy at University of Toronto, Kotra’s team uses target-based drug discovery and medicinal chemistry to discover novel antivirals for clinical applications.
Kotra’s team is working on developing effective drugs for a number of diseases, combining principles from medicinal chemistry, biochemistry, drug design, pharmacology and disease pathology to evaluate the effectiveness and investigate the molecular basis of action for several drug candidates. We are also teasing out the benefits of medical cannabis, studying the composition of various strains of medical cannabis and actively investigating its relevance to treatment of various neuro and inflammatory conditions. We are humbled to say that we are among the leading groups in Canada working to uncover the medicinal chemistry of cannabis and lead clinical studies of its use.
Our research group is studying ways to prevent progression of MS, and repair and reverse neuronal damage, with the goal of bringing the treatment to patients. With a very productive collaborative network in Toronto and in Canada, we are advancing the lead compound for potential clinical studies.
We have also collaborated with other teams to develop a groundbreaking compound to potentially cure diabetic neuropathy, now in clinical trials.
Impact and Accomplishments. Below are the accomplishments of Kotra group and the industry groups that Dr. Kotra led.
Pharmaceuticals
Multiple Sclerosis: The development of Lucid-21-302, a first-in-class, non-immunomodulatory small molecule designed to halt demyelination by inhibiting protein arginine deiminase 2. My leadership on this project since 2013—following its initiation with a clinical collaborator in 2010—has moved the molecule through rigorous EAE and cuprizone animal models into its current status as a Phase 2 clinical candidate. This technology was licensed to Lucid Psycheceuticals (now Quantum BioPharma)
Diabetic Peripheral Neuropathy: The development of WST-052 (WinSanTor). This therapeutic approach utilizes a selective muscarinic acetylcholine receptor M1 (M1R) antagonist, pirenzepine, formulated as a topical cream to maximize bioavailability at peripheral nerve endings. WST-052 is currently pre-commercial and utilized under "Right-to-Try" in the USA. This technology is licensed to WinSanTor, Inc. USA.
Malaria: The discovery and advancement of 6-iodo-uridine (Kopakamal) from discovery to preclinical toxicology stage.
Natural Health Products/Dietary Supplements
Acute Alcohol Intoxication: Discovery and the commercial launch of unbuzzd™ (USA) (unbuzzd Wellness Ltd.)
Natural Health Products: The successful Health Canada registration of Qlarity™ (NPN: 80144141). (Quantum BioPharma)