Lakshmi
Kotra

Drug Development and Disease Diagnostics
Drug Safety
Molecular basis of drug targets and diseases

MaRS Centre
5th Floor Room 5-401,101 College Street
Toronto ON
Canada

Area of Research

Lakshmi Kotra leads a multidisciplinary research group investigating the intersection of medicinal chemistry, drug action, drug design, preformulations and pre/clinical studies. He leads research programs in neuro, inflammatory disorders and infectious diseases. Kotra’s laboratory has successfully translated or engaged in translation of basic research into advanced preclinical and clinical studies. Over the past 20 years, Kotra’s lab has maintained high standards to conduct cutting edge research, including various regulatory clearances to conduct research with controlled substances such as medical cannabis.

Current programs in Kotra’s laboratory include chemical/preclinical/clinical research on medical cannabis and cannabinoids and the effects of cannabinoids on various cellular and organ systems, antivirals in organ transplant, disease-modifying therapies targeting multiple sclerosis, discovery of small molecules targeting thrombocytopenia, and clinical development of Kopakamal as an antimalarial agent.

Research Challenge

Many common diseases still lack effective and/or curative treatments, and sometimes the only option is to “manage” the condition. 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.

Sometimes, 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.

Proposed Solution/Current projects

Located at the Krembil Research Institute, University Health Network, Kotra’s team uses target-based drug discovery and medicinal chemistry to discover novel antivirals for clinical applications. In collaboration with hepatologists at UHN, Kotra’s group is engaged in target-based drug discovery and development to address NAFLD.

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 numerous drug candidates.  They 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. They are currently the leading group in Canada working to uncover the medicinal chemistry of cannabis and lead clinical studies of its use.

The program on disease-modifying therapies has been ongoing in the Kotra lab since 2010. They are studying ways to prevent progression of MS, and repair and reverse neuronal damage, with the goal of bringing the treatment to patients. They have also collaborated with other teams to develop a groundbreaking compound to potentially cure diabetic neuropathy, now in clinical trials. 

Impact to date

Research conducted by the Kotra lab has led to the discovery of numerous technologies that have since been licensed to companies. Their ultimate goal is to bring research-backed and evidence-based solutions to patients as soon as possible.

They have discovered a potent antimalarial agent currently in advanced preclinical development, identified novel compounds targeting multiple sclerosis that are in preclinical development, successfully co-developed a cream for diabetic neuropathy that is currently undergoing phase 1 and 2 clinical trials, and worked with industry in implementing novel cannabis extraction technology for the development of medically relevant products.

Kotra has co-founded and/or licensed the technology to companies, including WinSanTor Biosciences, CannScience Innovations, Inc. (now Scientus Pharma, Inc.) and CIDAVA Innovations (2013-2017), to successfully advance the development of technologies and discoveries. These technologies are implemented in industrial production, and the discoveries are reaching the market.

Publications

PubMed


Keywords: drug discovery, medicinal chemistry, drug formulations, small molecule drugs, biologics, cancer, diabetes, neuropathy and pain, multiple sclerosis, malaria, viral infections, thrombocytopenia