Evaluation of innovative risk mitigation services in the context of dual crises of COVID-19 and overdose among people who use opioids in Vancouver, BC

This award is co-funded by Health Research BC, through CIHR’s Operating Grant: COVID-19 Mental Health & Substance Use Service Needs and Delivery Funding Opportunity.

 

Principal Investigators Dr. Kanna Hayashi, Research Scientist at the BC Centre on Substance Use (BCCSU) and St. Paul’s Hospital Chair in Substance Use Research and Assistant professor in the Faculty of Health Science at Simon Fraser University (SFU) along with Dr. Kora DeBeck, Research Scientist at the BCCSU and Associate Professor in the SFU School of Public Policy aim to conduct preliminary evaluation of two novel measures introduced by the BC government in March 2020 to address the dual crisis of overdose and COVID-19.

 

Specifically, these measures include expanding the opioid agonist treatment (OAT) prescription guidelines and pandemic prescribing of pharmaceuticals (e.g. opioids) to people who use illicit drugs. By providing pharmaceutical alternatives to the toxic illicit drug supply, the interventions are intended to reduce physical encounters involved in obtaining illicit drugs and the use of toxic street drugs, thereby supporting both overdose and COVID-19 prevention efforts. To date, however, the impacts of these interventions have not been evaluated.

 

The proposed BC-based research aims to fill critical knowledge gaps by examining the reach and preliminary impacts of pandemic prescribing and expanded OAT prescription services among people who use opioids in urban Vancouver. Through this work, the research team, which consists of highly productive investigators and knowledge users with direct clinical and policy expertise, seeks to inform efforts to improve the delivery and effectiveness of the interventions.


End of Award Update – April 2023

Most significant outputs so far

We have successfully conducted interviews with 1,264 people who use drugs (including 911 people who use opioids) in Vancouver between July 2020 and November 2021, meeting our target sample size. We have developed multiple infographic summaries of data from the first wave of surveys (conducted in 2020), showing access to and perceived effects of the risk mitigation services among people who use drugs. These findings have been shared with and presented to a range of stakeholders, including those involved in developing and implementing the clinical guidelines for opioid agonist therapies and risk mitigation prescribing.

 

In addition, three manuscripts have been developed in collaboration with people with lived/ing experiences, addiction medicine physicians, clinician scientists and policy makers. The first manuscript demonstrated low awareness of risk mitigation prescribing among people who use drugs has been published in Harm Reduction Journal, while the second manuscript that showed the inability to contact a medication prescriber when in need among individuals accessing opioid agonist therapy has been published in Addiction Science and Clinical Practice.

 

The third manuscript that examines access to opioid agonist therapy and risk mitigation prescribing/prescribed safer supply over time is currently under review for peer-reviewed publication. Additionally, two analyses (one that examine the impacts of risk mitigation prescribing/prescribed safer supply and another that characterizes preferred pharmaceutical opioids among people who use opioids) are currently in progress for peer-reviewed publication as well.

Impacts so far

Our study findings have already been utilized to inform the implementation of the Prescribed Safer Supply initiative. Building on the risk mitigation prescribing, the BC government launched the Prescribed Safer Supply initiative in 2021 and put more emphasis on overdose prevention. At their request, we shared our study findings with the BC Ministry of Mental Health and Addictions.

Potential influence

Our research has significant potential to continue to inform policies and programs regarding safer supply and opioid agonist therapies. Of note, as safer supply initiatives are rapidly evolving, we have amended our survey questionnaire on an ongoing basis in an effort to capture the potential impacts of policy developments in a timely manner. Importantly, we have engaged a range of stakeholders (e.g. people with lived/ing experiences, addiction medicine physicians, policy makers, etc.) in developing and updating the survey questions so that the data we collect are meaningful and useful for informing further developments of these new interventions.

Next steps

As more recently collected data have become ready for analyses, we plan to develop more infographic summaries and analyses/manuscripts in this area. As we have done to date, we plan to continue to engage stakeholders in developing and disseminating the research outputs.

Useful links

Tracking the Prevalence and Incidence of Modifiable Suicide Risk Factors During the COVID-19 Pandemic to Inform Targeted Suicide Prevention in British Columbia

This award is co-funded by Health Research BC, through CIHR’s Operating Grant: COVID-19 Mental Health & Substance Use Service Needs and Delivery Funding Opportunity.

 

Problem: Half of Canadians report worsened mental health since the COVID-19 pandemic began disrupting our lives this Spring. These impacts, combined with rising prevalence of known suicide risk factors such as unemployment and financial hardship, social isolation, alcohol and substance use, relationship strain and domestic violence, have raised concerns that of rising suicide risk in the Canadian population. Canada loses 3,800 to 4,500 lives to suicide each year. Suicide death and bereavement confer long-term psychological and social risk to families and communities. A small increase in suicide rate can thus result not only in excess loss of life, above and beyond the direct impacts of the pandemic, but also confer long-term vulnerability in our communities.

 

Research: In collaboration with an international team of researchers led by investigators Shanaya Rathod and Peter Phiri in the UK, our Canadian team aims to characterize the specific mental health and related cognitive impacts of the COVID-19 pandemic to inform evidence-based policy that can mitigate secondary mental health and suicide risk. We will conduct three pan-Canadian general population surveys, in September 2020, December 2020, and March 2021. For each survey, we will recruit at least 5,000 community adults, balanced by sex, age, and geographic region. Surveys will focus on Canadians’ emotional, physical, and cognitive wellbeing across distinct phases of the pandemic. In addition, we will work with mental health service leaders, providers and users to co-create supplemental surveys to assess the mental health experiences and needs of three potentially vulnerable groups: frontline health workers, Indigenous peoples, and people living in rural or remote areas. Our results can inform mental health strategies by identifying where, with whom, and what kind of intervention is needed to effectively reduce suicide risk in the population. Support from MSFHR and the BC Ministry of Health will enable us to over-sample British Columbians so that we can understand mental health needs within this province and identify sectors or populations with mental health needs.

 

Research Team: Our interdisciplinary research team, led by Co-PIs Brianna Turner, Theone Paterson, and Chris Lalonde, includes psychology, social work, and sociology researchers, as well as community knowledge users representing the United Way of the Lower Mainland, the Ontario Association of Social Workers, and the Canadian Mental Health Association.

 

Website: https://onlineacademiccommunity.uvic.ca/covidmentalhealth

 

Keywords: Suicide Prevention, Mental Health, Sleep, Depression, Substance Use, Social Connectedness, Public Health, Survey

 


End of Award Update – June 2023

Most significant outputs so far

This study examined mental health impacts of the COVID-19 pandemic across adults in three large samples of Canadians (Ns=5000-7000). We learned that older adults reported better mental health and more social connectedness relative to younger adults during the pandemic. Loneliness predicted negative mental health across all ages, while social support buffered the effect of loneliness in older adults.

We also observed slight increases in rates of suicidal ideation (SI) across the three surveys, from 4.1% in the first survey (Fall 2020) to 5.8% in the final survey (Fall/Winter 2021). Odds of reporting SI were higher for survey respondents who were under 35 years old, had pre-existing mental health concerns, had quarantined due to suspected or confirmed COVID-19 exposure, encountered potential exposure to COVID-19 at work, were medically vulnerable toward COVID-19 infection, and were insecurely employed or unemployed. These associations, in turn, were mediated by psychological experiences, particularly depression and thwarted belongingness. We are working to further understand vulnerability to suicidal thinking in our data, and to identify possible policy targets to bolster mental health.

 

Impacts so far

We have shared our results with the CanCOVID network, at a BC Ministry of Health Knowledge Translation event, and the Canadian Psychological Association and American Association of Suicidology.

We published several open access, peer-reviewed papers, including reports on predictors of suicidal ideation, social connectedness in older adults, and vaccine hesitancy during the pandemic.

We will share additional publications and reports on our study website.

Potential Influence

We are working on developing a set of videos this summer to summarize main study results, which we hope will increase uptake and impact among the general public as well as policy makers and health professionals.

 

Next Steps

We are currently analyzing the data gathered through two specialized surveys that we conducted, focused on mental health among healthcare workers and people living in rural and remote communities in BC.

 

Addressing the dual public health crises of COVID-19 and overdose

This award is co-funded by Health Research BC, through CIHR’s Operating Grant: COVID-19 Rapid Research Funding Opportunity – Social Policy and Public Health Responses. 

 

A team led by Dr. Amanda Slaunwhite, Senior Scientist with the BC Centre for Disease Control and an adjunct professor in the School of Population and Public Health will assess the impact of the new risk-mitigation guidance that permits prescribing of pharmaceutical alternatives to the toxic drug supply. Researchers will determine the effects of the pandemic and risk mitigation measures on COVID-19 infection, continuity of care for treatment of substance use disorders and non-fatal and fatal overdose in BC. The researchers will also identify barriers and facilitators to implementation from the perspectives of people who use substances, prescribers, harm reduction workers, and other providers and community members.

 

The team is led by principal investigators at UBC, the Canadian Institute for Substance Use Research (CISUR) at the University of Victoria (Dr. Bernie Pauly and Dr. Karen Urbanoski) and Simon Fraser University (Dr. Bohdan Nosyk and Dr. Natt Hongdilokkul). The team includes co-investigators and collaborators from the First Nations Health Authority, Ministry of Mental Health and Addictions, BC Centre on Substance Use, the BCCDC-based Compassion Inclusion and Engagement (CIE) (PEEP) peer network, Provincial Health Services Authority, BC-Yukon Association of Drug War Survivors and Public Health Agency of Canada.


End of Award Update – August 2023

 

Most exciting outputs so far

Briefly, our research activities to date suggest that prescribed safer supply has many benefits to persons who receive medications, however implementation and access was uneven across the province. Prescribed safer supply opioids have reached approximately 7,000 persons since March 2020 and indications from preliminary administrative health data suggest that the intervention may protect against mortality. Participants who received safer supply reported many positive benefits, however access to these medications is very limited due to limited prescribers.

The project is concluding over the next few months as we transition into a new CIHR-funded longer-term evaluation project. As of June 2022, we have pivoted from data collection and analysis to knowledge translation activities including the development of peer reviewed manuscripts. There are over 10 manuscripts under development.

We have published the study protocol in BMJ Open. We have also publicly posted Knowledge Updates and Infographics about emerging results on the BCCDC website. These results have also been disseminated through the BC Overdose Emergency Response Centre list-serv. Some examples are:

Knowledge translation has been ongoing since the project began. Our knowledge translation efforts are co-led by persons with lived experience who have been heavily engaged in the project. There has been international and national interest in this project and we have been invited to present to many audiences including the New Zealand Drug Foundation:

Impacts so far

This project has had a direct impact on the Province of BC’s prescribed safer supply policy directive and program implementation strategies. The results of this project are cited in several policy and clinical guidance documents including: 

Potential Influence

This project has had a significance influence on our future research activities by providing an opportunity for researchers from UVic, SFU and UBC to partner with persons with lived experience, the First Nations Health Authority and other health system partners to work together to better understand prescribed safer supply in BC. These partnerships have led to many new successful grants from CIHR, Providence Health Care, Health Canada and the Office of the Representative for Children and Youth.

Next Steps

We have several new grants, including awards from CIHR and Health Canada, that have been funded in the past six months to continue our work in this area. This includes three projects:

  • Mathematical Modeling Prescribed Safer Supply (NPI: Nosyk) – Funded by CIHR, 2021-2024
  • Evaluating prescribed safer supply among formerly incarcerated persons during an overdose public health emergency (NPI: Slaunwhite)- Funded by SUAP Health Canada, 2022-2023
  • A mixed methods evaluation of safer supply initiatives to reduce illicit drug overdose in BC (NPI: Urbanoski) – Funded by CIHR, 2022-2026

Extracellular vesicle associated glycans as a novel platform for breast cancer detection

Health Research BC is providing match funds for this research project, which is funded by GlycoNet’s Collaborative Team Grant. 

 

Breast cancer is the most common cancer amongst women in Canada. Breast cancer cells shed tiny pieces of themselves into the blood stream called extracellular vesicles. These tiny pieces, or cell fragments, are different from those of a healthy breast cell and we think they could be used to detect a breast cancer at its earliest stage. Importantly, we can isolate and study these fragments from the blood of healthy females and breast cancer patients. We think that by looking at the sugars and proteins they contain we will find markers that could help in the detection of breast cancer. We are also going to look at tumor cell fragments from patients whose cancer came back years after treatment, a process known as metastasis, and find unique markers that could predict this outcome. By identifying breast cancer early and figuring out whose at risk for a having their cancer come back we can improve how women are treated and reduce the chances of the cancer coming back.

 

This Pan-Canadian project involves research teams in British Columbia and Alberta. Dr. Williams, lead PI, is an assistant professor at UBC’s Faculty of Pharmaceutical Sciences and her team includes clinical pathologist Dr. Peter Watson (BC Cancer) and Professor of Chemistry Dr. Lara Mahal (University of Alberta).


End of award update: November 2021

 

Most exciting outputs

Our project successfully isolated small cell fragments, termed extracellular vesicles, from blood plasma of hundreds of breast cancer patients and healthy females. From this, we were able to look at the sugars and proteins on these fragments to identify ones unique to breast cancer patients. This has allowed us to find a couple unique markers that we think can be used to identify breast cancer at its earliest stage of development.

 

Impact so far

Detecting cancer at the earliest stage will support the best outcome for patients. This is particularly relevant in breast cancer as it is well established that a disease diagnosis at an early stage, Stage I, is associated with the highest rates of patient survival. Our project has identified novel sugar and protein based biomarkers with utility in identifying breast cancer. Validation of newly identified biomarkers could lead to the development of a blood-based test for breast cancer screening.

 

Potential future influence

Our project aims to reduce the mortality associated with a breast cancer diagnosis. To do this we are aiming to develop a non-invasive test that will support the detection of breast cancer at its earliest stage.

 

Next steps

We plan to validate our newly discovered breast cancer biomarkers and work towards translating our results into a product that could be used as a simple point-of-care test by a family doctor.

Please visit GlycoNet to learn more about this project.

Ventilation heterogeneity in asthma, COPD and asthma-COPD overlap: oscillometry and pulmonary MRI

Airways disease is a hallmark finding in both asthma and chronic obstructive pulmonary disease (COPD). Although tobacco cigarette smoking is the largest known cause of COPD, recent studies have revealed that 10% of patients with life-long asthma may develop COPD later in life without ever smoking. The mechanisms underlying asthma transition to COPD are unknown. To better understand this transition, this proposal will use 129Xe magnetic resonance imaging (MRI), computed tomography (CT) imaging and oscillometry to measure airway abnormalities in patients with asthma, COPD, and asthma-COPD overlap. These measurements will provide a better understanding of airway abnormalities that contribute to development of COPD in these patients with asthma. COPD is the most common cause of hospital admission in Canada and treatment costs in BC alone are estimated to be over $600M/year. The results generated from this proposal may identify new ways to treat COPD or halt its development in patient with asthma, contributing to reduced hospital admissions and costs related to COPD.


 

End of Award Update – March 2024

 

Results

With the emergence of long COVID, we pivoted our novel lung imaging methods to investigate the lungs of people who experienced COVID-19 infection with persisting, long term symptoms over 1-year after infection. In collaboration with colleagues at the University of Kansas Medical Center and Duke University, we created a multi-centre dataset of patients with long COVID to better understand how long COVID may differ across different patients. We used xenon gas magnetic resonance imaging (MRI) to measure how effectively the lungs of patients with long COVID were performing gas exchange (the main function of the lungs). Our results showed that there are 4 different sub-types of long COVID that have different lung abnormalities. We anticipate that the xenon MRI results can be used to help determine appropriate treatment for patients experiencing long COVID.

 

Impact

In our centre, the xenon MRI results have been used to help determine appropriate for different patients with long COVID. Our results uncover the lung-specific abnormalities that are related to long COVID.

 

Potential Influence

We anticipate these results will help to better understand and classify patients with long COVID, towards appropriate treatment and alleviating patient symptoms.

 

Next Steps

We are using similar xenon MRI methods to investigate other forms of lung exposures including cigarette smoking, cannabis smoking, and vaping.

 

Useful Links

https://erj.ersjournals.com/content/early/2024/02/02/13993003.02301-2023

Vitamin C-induced epigenomic remodeling as a preventive therapy for leukemic transformation

Despite the overall improved diagnostics, standard of care and therapeutic options, most acute myeloid leukemia (AML) patients suffer from severe therapy-related side effects and still only 28% of them reach 5-year overall survival. The hypothesis that drives my project is that mutations which affect DNA-modifying enzymes disrupt a methylation-based control mechanism that regulates gene expression in a way that halts the normal cellular differentiation process. The discovery that vitamin C acts as an enzymatic co-factor that is able to revert this methylation defect in affected cells, provides a unique opportunity to transfer this knowledge to the development of novel, less toxic treatment strategies for patients that harbour these mutations. Within the scope of this project, I plan to explore whether and to which extent I can restore the normal DNA methylation signature in patient-derived leukemic cells in mice, either through vitamin C treatment alone or in addition to Health-Canada approved AML drugs. Further, I will explore the potential of vitamin C treatment to delay or prevent the transformation of not yet leukemic cellular states towards myeloid malignancy.

 


 

End of Award Update – August 2023

Most significant outputs

The most exciting results are yet to come: two manuscripts are currently in preparation to be submitted to Genome Biology and Leukemia within the year.

 

Impact

Despite the overall improved diagnostics, standard of care, and therapeutic options, most acute myeloid leukemia (AML) patients suffer from severe therapy-related side effects and only every third patient reaches 5-year overall survival. An observation that formed the foundation for this project is the frequent occurrence of mutations in AML cells which affect enzymes that contribute to a special control mechanism that regulates if and how much of a gene is read from our DNA to produce functional proteins. This control mechanism involves the precise placement and removal of “methylation marks” – either directly on top of the DNA strands or at proteins that help to organize the DNA into the three-dimensional structure we call chromosomes. If the placement or removal of these methylation marks is altered, protein production and cell survival mechanisms are disturbed as a consequence – a characteristic which we often observe in cancer cells. In the past, our lab contributed to the discovery that vitamin C acts as a co-factor that helps to re-activate the enzymes that deposit and remove methylation marks, even despite their mutations. Thus, treating affected AML cells with vitamin C can help to revert their methylation defect, which directs their gene expression to a healthier state and causes cancer cells to die under controlled laboratory conditions. As vitamin C is a non-toxic, well-tolerated, widely available, and cost-effective substance, its potential anti-cancer effect provided us with a unique opportunity to test whether this knowledge could be translated into effective but less toxic alternative treatment strategies for AML patients who harbour these mutations.

 

Within the scope of this Health Research BC and Lotte and John Hecht Foundation co-funded project, we have created murine leukemia model systems that allowed us to confirm the vitamin C anti-leukemic effect in living organisms. Interestingly, while studying these models more deeply, we observed that not all cells within a pool of leukemia cells responded equally to vitamin C – whereas most cells matured and died, there seemed to be some cells that were able to survive the treatment despite carrying the same disease-initiating mutations. This observation directly impacts the potential to utilize vitamin C in a therapeutic setting, arguing that even among AML cases that display the same disease-driving genetic abnormalities, not all patients will respond to vitamin C. Also, these findings are consistent with clinical observations, where historically, vitamin C was reported to be both highly effective and not effective at all in a series of trials in the 1970’s and 80’s that assessed the activity of vitamin C against terminal stage solid cancers.

 

Potential Influence

In the remaining months of finalizing this project, we are focusing on identifying what makes some cells sensitive and others tolerant to vitamin C, despite the presence of the same disease-driving mutations. Therefore, we have selected individual cells from a pool of mutation-positive AML cells which display the ability to produce a leukemia-like myeloid cell hierarchy in a culture dish. Through repeated treatment and testing, we could identify both model hierarchies that repeatedly tolerated or succumbed to the presence of vitamin C. As each cell within a model hierarchy stem from a single ancestor cell, we hypothesize that it is the maturation state of the ancestor cell – in combination with the present mutations – that mediates the observed differential vitamin C responsiveness. Further, we argue that we will be able to observe this difference in maturation state in a cell or a hierarchy’s DNA methylation patterns. We are working to confirm this hypothesis to define a diagnostic molecular signature (a so-called biomarker) that might help decide which AML patients can benefit from vitamin C in a clinical setting.

 

Next Steps

This research will be continued in the Hirst lab; however, I will move on to a new position soon as the time I am allowed to work as a postdoctoral fellow in Canada is coming to an end

Resisting Vascular Cognitive Impairment: The Effects of Resistance Training on Myelin and Blood-based Biomarkers of Neuroplasticity in Older Adults

We are studying if strength training exercises can reduce myelin loss and preserve cognitive abilities in adults with cognitive impairment due to vascular risk factors (e.g., high blood pressure), also known as vascular cognitive impairment (VCI).

Worldwide, VCI is the second most common cause of dementia and it is associated with myelin loss. Myelin is a component of neurons critical for transmission of brain signals. Thus, myelin is important for the maintenance of cognitive (i.e., thinking) abilities. Animal studies suggest myelin loss may be minimized with physical exercise. The objective is to determine whether strength training (e.g., lifting weights) is an effective strategy for slowing down myelin loss in persons with VCI.

We will conduct a 12-month study with 88 adults with VCI; half will receive strength training and half will receive balance and stretching exercises. At the end of study, the two groups will be compared on myelin content and cognitive function. Reducing myelin loss could preserve cognitive abilities in adults with VCI and reduce their risk of dementia. Our proposal is also timely as the prevalence and burden of VCI will only increase with the world’s aging population.

Promoting mental health in immigrant, refugee, and non-immigrant children: A British Columbia intergenerational population cohort study

Mental health problems are estimated to be the most common disabling condition among adolescents worldwide, with children growing up in socially disadvantaged homes having up to three times the risk of mental health problems compared to children without such disadvantage. Studies show a high degree of intergenerational stability in these patterns, with social stressors putting particular subgroups of children at higher risk from the earliest stages of development. Immigrant and refugee children make up a significant proportion of the BC child population, and have a unique set of circumstances that may increase or decrease their risk of mental health problems as they reach adolescence. In BC, an established system of child development monitoring paired with new data linkages to provincial health, immigration, and Statistics Canada records create a globally unique opportunity to investigate continuities from maternal mental health problems to childhood emotional symptoms and adolescent mental health problems, for immigrant, refugee, and non-immigrant children. The purpose is to identify opportunities to break these continuities, informing the timing and design of preventative interventions to promote population mental health.


End of Award Update: December 2022

 

Most exciting outputs

This project opened a door for me to contribute to two integrated knowledge translation studies monitoring family, child, and youth
mental health during the COVID-19 pandemic. Working together with researchers and stakeholders from public mental health and
government, we brought urgent attention to pandemic-related population mental health trends among BC families and young people
through research reports, a policy brief, an op-ed, media interviews, and eight published articles. I was excited to at the same time
complete my original study on mental health among immigrant, refugee, and non-immigrant children and present these results at the
International Population Data Linkage Network Conference in 2022. Findings from this study suggested that BC children with
immigration backgrounds enter school with lower emotional health than children with non-immigration backgrounds and are likely to
benefit from increased social supports.

Impacts so far

Our research on child and youth mental health during the pandemic was referred to during a Debate of the BC Legislative Assembly
and referenced in a BC Ministry of Education report on Key Principles and Strategies for K-12 Mental Health Promotion in Schools. I
also had the opportunity to present this research to over 100 health professionals through the Centre for Health Evaluation and
Outcome Sciences Work in Progress seminar series, drawing attention and inviting conversation around the pandemic recovery
response for supporting the mental health of families and young people in BC.

Potential future influence

The connections I have made with researchers and stakeholders through this award have initiated a pathway for what I hope will be
many future opportunities to synergize between research, health services, and policy to make collective population health impacts at a
systems level.

Next steps

I will continue collaborating with colleagues and bridging connections between research and practice in my new role in a health
services research and evaluation position. Results from the immigration mental health study have been selected for submission to a
journal special issue and will hopefully become available in 2023!

Useful links

Related videos

Watch this presentation on the mental health impacts of the COVID-19 pandemic on students, parents, and teachers, produced for the Centre for Health Evaluation and Outcome Sciences (CHÉOS) Work in Progress Seminar Series, featuring Anne Gadermann, Kimberly Thomson, and Monique GagnĂ© Petteni.

 

Development of Novel Alpha-amanitin Analogs for Targeted Cancer Chemotherapy

New toxins for incorporation into treatments known as antibody-drug conjugates are urgently needed to ensure therapeutic action. These antibody-drug conjugates consist of an antibody, designed to target a specific group of cells, attached to an active drug that elicits a desired cell response. While most emergent payloads for clinical application target tubulin, making them redundant, the death cap mushroom contains a toxic peptide called alpha-amanitin with unique biological activity. Amanitin presents its toxicity by preventing the conversion of DNA to RNA, a process required for protein synthesis. This inhibition ultimately leads to cell death.  Amanitin’s high toxicity provides potential for a low dose cancer therapeutic if general toxicity to non-cancerous cells can be avoided. I seek to investigate the feasibility to harness amanitin’s bioactivity while delivering the toxin specifically to cancer cells by attaching a targeting agent. In order to facilitate these investigations, I will develop a scalable method to generate substantial amounts of the toxin. By utilizing this targeted approach, we anticipate a cancer cell-specific delivery of the toxin, which in turn would attenuate the off-target effects and general toxicity.

Modulating microRNA-193a expression levels as a treatment for acute myeloid leukemia (AML)

Acute myeloid leukemia (AML) has a dismal prognosis in Canada with only every 5th patient surviving 5 years. To find novel treatment options, we explore the therapeutic potential of the tumor suppressor microRNA (miR)-193a in AML patients together with InteRNA, a company that developed a novel drug based on the liposomal encapsulation of miR-193a (1B3), which showed very promising preclinical results in solid tumors and provided the rational for a phase I trial starting in spring 2020. We and others have previously shown that miRNAs are small RNAs that impact leukemia cells and are an emerging class of drugs. Recent data from our group showed a strong leukemia inhibition via miR-193a in animal AML models, highlighting the tumor suppressive effect of this miRNA. In addition, we are studying the regulation of miR-193a in AML cells to develop strategies to reinstate miR-193a expression and thus enhance its tumor suppressor function. This innovative study pioneers a novel class of RNA-based drugs in the treatment of AML and the groundwork for future clinical trials.