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MitoCanada partners with MITO2i to fund mitochondrial research that could introduce new therapies for Alzheimer’s disease

Alzheimer’s disease is one of hundreds of illnesses that Canadians suffer from. The disease stems from mitochondrial dysfunction, however, the underlying molecular mechanism and how it contributes to the development of disease remains poorly understood. 

Alzheimer’s disease in patients and mouse models exhibits an imbalance between mitochondrial fission and fusion. This change in dynamics within the mitochondria has significant consequences on how electrical signals move from one nerve cell to another as well as how the nerve cells themselves function.

Re-establishing an equilibrium within mitochondrial dynamics and structure may be a potential therapeutic target for recovering mitochondrial function and neuronal homeostasis which is the process by which organisms react to specific conditions while trying to maintain their stability and survival.

Dr. Royeais investigating the significance of Sigma-1-receptors medicines and their impact on mitochondrial function. She hopes her future research will identify whether the FDA approved, pain relieving drug, Pentazocine, can be repurposed for the treatment of Alzheimer’s disease as well as other mitochondrial-specific diseases.

Jessika Royea, PhD| Postdoctoral Researcher, University of Ottawa

Principle Investigator Mireille Khacho, PhD | Assistant Professor and Canada Research Chair, Department ofBiochemistry, Microbiology & Immunology, Ottawa Institute for Systems Biology, Faculty of Medicine

MitoCanada funds research to advance Rapid Diagnosis of Mitochondrial Disease: Reducing diagnostic timing from years to days through generation sequencing

Research Project: MITO-FIND 

Mitochondrial Functional and Integrative Next generation Diagnostics

Individuals with mitochondrial disease will see, on average, eight doctors before receiving a diagnosis. Traditional methods of diagnosis include painful and invasive muscle biopsies, the results of which can take months to come back to the clinician. 

At the University of Calgary, Dr. Aneal Khan conducts leading edge mitochondrial research focused on rare and inherited metabolic and genetic disorders. 

MitoCanada granted $75,000 to Dr. Khan for the MITO-FIND project. These funds were also matched This innovative research study was designed  to implement a rapid process to diagnose mitochondrial disease using next generation sequencing. The funding was applied to perform gene sequencing on patients presenting either in hospital or in clinic with a suspected mitochondrial disease.  This included mostly reagent costs but also labour to run the gene sequencing.

Dr. Khan developed sequencing methods to provide next-day diagnostic results from gene sequencing for patients suspected of a mitochondrial disease. His methods eliminate the need for a muscle biopsy in the majority of patients and, in some cases, shorten the time to diagnosis from two years to two days.

These mitochondrial-targeted rapid sequencing methods can be applied to any sample from a simple cheek swab and provide results to anyone in the world.

Mitochondrial diseases have high morbidity and mortality rates. While the diagnostic task was made easier by the MITO-FIND project which sets a new standard for diagnosing mitochondrial disease, it is important to note that until a cure is found, we need to continue efforts to find effective treatments, improve access to diagnosis across Canada and help families living with mitochondrial disease. We need to understand how to improve lives of patients using existing drugs as well as developing new drugs.

Dr. Aneal Khan | Professor of Medical Genetics and Pediatrics, University of Calgary Cumming School of Medicine 

MitoCanada Has been instrumental in proving an opportunity to advance the art of diagnosis of mitochondrial diseases in Canada. –Dr. Aneal Khan

MitoCanada funds research to support the development of novel therapies to treat mitochondrial diseases

Exerkines™are a recently discovered class of biologically active compounds, such as peptidesandRNA, that are released into the circulatory system when we exercise. These compounds, which were discovered and named by Dr. Mark Tarnopolsky, have beneficial effects on various tissues and organs. 

While exercise has been associated with numerous health benefits for decades, there may be additional advantages we had not considered.  In 2016, MitoCanada supplemented a research grant from the Canadian Institutes of Health Research (CIHR) provided to Dr. Tarnopolsky and his then Ph.Dstudent, Dr. Justin Crane. The purpose of the research was to look at the effects of exercise on the release of exerkine™proteins into the circulation. 

Through their research, they discovered that Interleukin-15(IL-15)went up in response to acute exercise. IL-15 plays a majorrolein the development of inflammatory and protective immune responses. 

Perhaps more important to our community, they also found that very tiny pulses of IL-15 released in response to acute exercise led to the production of mitochondria in skin and muscleof mice.

Applying this new knowledge that exercise can impact mitochondrial function, this discovery could be used in future therapies for treating mitochondrial disease.Specifically, IL-15 could potentially be part of an injectable therapy (like an insulin pen) that delivers some of the mitochondrial benefits of exercise in those who cannot perform exercise. 

Discoveries like this offer hope to our mitochondrial community.

Dr. Mark Tarnopolsky | Professor of Pediatrics and Medicine McMaster University

MitoCanada partners with MITO2i to fund mitochondrial research that could introduce new therapies for breast cancer 

Breast cancer is the number one cancer killer of women. 

Improving survival and quality of life for patients with breast cancer is essential. We are however,  limited by our ability to offer personalized therapies that reduce the risk of treatment-resistance and disease recurrence while minimizing the risks of toxicity associated with ineffective chemotherapeutic agents. 

Therapy for patients with locally advanced breast cancer typically involves treatment with chemotherapy prior to surgery. Selecting the appropriate therapy often involves significant trial-and-error. Most patients receive a standard cocktail of drugs, but only about one-third have a positive and complete response. This highlights the need for personalized treatment. 

Dr. Screaton and his team propose to identify genes in the mitochondria of cancer cells that maycontribute to their growth, survival and ability to develop resistance to chemotherapy. 

It is known that cancer cells can use nutrients differently than normal cells. This raises the possibility of new strategies to kill them. These are called ‘mitochondrial metabolism vulnerabilities’. 

This novel approach will be able to silence mitochondrial genes in locally advanced breast cancer cells taken directly from patients to identify tumour-specific vulnerabilities. These vulnerabilities can then be targeted alone, or in conjunction with lower doses of established therapies, to kill tumours more effectively and reduce side effects. 

An exciting outcome of this work is the development of patient-specific therapies based on the patient’s tumour’s demonstrated drug sensitivities.

Robert Screaton, PhD | Senior Scientist at Sunnybrook Research Institute