|This month we hear from Manuela Neuman, who joins Maria Shipkova as co-editor of our E-News. Manuela shares about her extensive experience, and her special contribution to understanding and diagnosing drug reactions of various types. Among her contributions is the Lymphocyte Toxicity Assay, an innovative diagnostic test that helps predict the drugs patients will react to, allowing the safe selection of therapy.
Associate Professor, Faculty of Medicine, University of Toronto
CEO & CSO, In Vitro Drug Safety and Biotechnology,
Banting Institute, Toronto, CA
Can you tell us a little bit about your respective roles? What is a typical day like for you?
I am the founder and Chief Scientific and Executive Officer of In Vitro Drug Safety and Biotechnology at the Banting Institute in Toronto. In this position, I consult clinicians from all around the world regarding their patients that have a hypersensitivity reaction to therapeutics, complementary and alternative medicine, herbal remedies or interaction between the disease and drugs of use and misuse. I design the experimental and clinical studies for drug discovery and therapies for several Pharmaceutical companies. In addition, I ensure that the analytical laboratory is operating according to guidelines for clinical testing. I certify that the reports for patient results are correct and I provide the needed interpretation. Moreover, I implement, develop and validate drug tests by immunoassay. I also interact with laboratory technicians and hospitals to monitor information.
My responsibilities include making recommendations for new tests to develop, as well as validating drug tests by immunoassay instrumentation or specific kits. I interact with external customers of several organization to facilitate and foster the transfer of clinical information to help support patient care and patient education. In addition, I organize international conferences, symposia and workshops for IATDMCT, as well as various clinical chemistry associations. Finally, I collaborate with other specialists to promote pharmaco-vigilance and pharmaco-justice.
I specialize in Clinical Chemistry, Pharmacology and Toxicology. I am appointed as Associate Professor in the Department of Pharmacology and Toxicology, Associated Global Health at the Faculty of Medicine, University of Toronto, Canada. In this position, I teach Pharmacology as well as Clinical and Experimental Toxicology and Pathology. I am experienced in scoring liver pathology, especially drug-induced liver injury, herbal induced liver injury, patients with alcoholic, non-alcoholic and viral hepatitis. I performed this function for many hepatitis clinical trials. I also conduct many studies using immunohistochemical and electron microscopy on liver biopsies from patients with autoimmune diseases. I continue to author papers on therapeutic and drug monitoring in patients with drug induced idiosyncratic reactions in the gastro-intestinal system. I have patents on biomarkers that can be used in studying the efficacy of therapeutic intervention in reducing liver fibrosis, inflammation and repair in gastro-intestinal system.
For years, I have hosted graduate students of all levels, as well as international researchers in my laboratory. Clinical Chemists, Researchers and Clinicians spend time in my lab learning new techniques in order to be able to adapt these to their needs back home. Other important research outcomes include efficacy of therapies, expression of pathogen recognition receptors, and signalling pathways involved in liver injury. Using personalized medicine approaches, targets are reached more quickly and regularly, which improves clinical outcomes.
Is there anything that your laboratory does, or that is done at your hospital, that you would consider innovative?
Certainly, our proprietary Lymphocyte Toxicity Assay is an innovative diagnostic test. This innovation in diagnostic testing leads to focused and efficient therapeutic interventions, which reduces unwanted adverse events and health care costs. We have been able to apply the test successfully in clinics. The patients that need a certain medication to maintain their health may be sensitive to a certain drug. Using the Lymphocyte Toxicity Assay we can determine which medication might produce an unwanted adverse event and which medication can be administered safely. Our task is to transform health care through the promotion of specific biomarkers and implementation of personalized medicine. The laboratory is expanding its conventional biochemical non-invasive biomarker services to include new cutting-edge procedures. These services are intended to lead to novel therapeutic targets which will serve the clinical and scientific community.
In Vitro Drug Safety and Biotechnology provides unique services involving the isolation of different cell types. The most powerful outcome ensues when our services are applied to the in vitro models of liver fibrosis, allowing direct analysis of specific cellular changes in the evolution of diseases. The laboratory has tests for anatomic pathology, pharmacogenetics, immunology, infectious disease, dermatology, gastroenterology and neurology. This involves clinical trials, pharmaco-vigilance, as well as commercial testing for the pharmaceutical and biotechnology companies. In Vitro Drug Safety and Biotechnology amasses the expertise of clinical biochemists, pharmacologists and toxicologists that are involved in the discovery of specific disease ‘signatures’ and the development of cell-based technology. Our network is linked to clinicians in a variety of public health associated areas.
What technological innovations have entered into use during your career that have permitted a change, or evolution, in practice?
The instrumentation leading to technical possibilities of the technicians; the capture of the data changed and the amount of data published has significantly augmented. Advanced technological communication between clinical chemists around the world has permitted speedy knowledge exchange.
How did you become interested in your area of expertise?
I began my career as a researcher in the drug discovery field. However, diagnostic and precision medicine attracted me. I completed my PhD in Physiology and Pharmacology in parallel to my work in clinical chemistry. The subject of my doctoral thesis was “The hepatotoxicity of Hornet venom”. This was the first zoological product that was demonstrated to produce liver injury in humans. I was fortunate to work with the late Professor H. Zimmerman, who initiated the study of hepatocytotoxicity. This was the beginning of my work on drug and natural products inducing adverse effects.
Working at The Hospital for Sick Children in Toronto, I saw that many therapeutic medications could produce liver injury and severe cutaneous adverse reactions that can provoke irreversible damage, leading to death. The need for personalized therapy lead me to discover the Lymphocyte Toxicity Assay which is able to distinguish between a drug that produces hypersensitivity reactions and another drug that does not produce harm. Our proprietary test from 2000 can predict the drug that can be administered safely to the individual.
Is there anything that you’ve seen or heard about recently and thought “I’d like to incorporate that idea at my center”?
Biological therapies, such as Remicade (infliximab, anti-tumor necrosis factor), tofacitinib, (small-molecule Janus kinase inhibitor), Prolia (denosumab, anti-RANKL) are successfully used in clinics to induce and prevent inflammation in several diseases. However, there is a possible adverse event which occurs regularly in patients during the therapeutic intervention. I would like to identify specific cytokines as biomarkers for the prognosis and diagnosis of drug-induced toxicity caused by new biological therapeutics. Additionally, I would like to continue looking at the possible role of viruses in drug-induced hypersensitivity reaction.
What sort of research do you have on the horizon that you think might influence clinical practice in the future?
In many countries, Cannabis sativa is considered ‘the medicine of the future.’ Although targeted therapies to treat specific diseases, such as pain and opioid addiction, are published, there is an urgent need to research its role in personalized medicine, to identify the clinical toxicological aspects of misuse and interaction with other medications and herbs. The use and misuse of Cannabis can influence clinical practice. Additionally, the use of herbal remedies can interfere with analytical methods.
What do you consider is the future for TDM and CT? What are you excited about? What are the challenges we face?
In my opinion the future of TDM and CT will expand to include environmental sciences. I am excited about new technology that will permit translational research in Clinical Toxicology to be extended to environmental studies, drug testing in several industries, and immuno-pharmaco-genetics and pharmaco-justice. We face many challenges, such as efficient and effective international collaborations, interdisciplinary teams that would include computational sciences, as well as new technologies.
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