Research in Dr. Côté’s Lab
Research in Dr. Côté’s Lab concentrates on the mitochondrial toxicity of drugs, primarily antiretroviral drugs used in HIV therapy. The use of highly active antiretroviral therapy (HAART) (triple therapy) has significantly decreased mortality in the HIV infected population. However, HIV therapy is not a cure and treatment is life-long. As HIV infected individuals survive longer, the toxicity of the drugs and their resulting side effects are becoming a significant cause of morbidity and mortality, not to mention a cause of non-adherence to prescribed therapy. The drugs can cause mitochondrial DNA (mtDNA) depletion through inhibition of the mtDNA replication by the mitochondrial polymerase gamma, as well as mtDNA damage through mutation/deletion.
Recently, drug-induced changes in mitochondrial gene expression have also been observed. All these can lead to mitochondrial dysfunction in various tissues and a myriad of toxicity symptoms including lipoatrophy, peripheral neuropathy, hyperlactatemia/lactic acidosis, liver failure, renal failure, pancreatitis, wasting, fatigue, some of which can be fatal. Some antiretroviral drugs can also inhibit telomerase, the enzyme complex that elongates telomeric DNA. The effect of antiretroviral drug exposure during early fetal development, childhood and adulthood on telomere length is also a topic of interest in this lab.
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Antiretroviral mitochondrial toxicity and telomere attrition in infants born to HIV-infected mothers.
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Antiretroviral mitochondrial toxicity and telomere attrition in HIV-infected adults and children, as well as during pregnancy.
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Mitochondrial toxicity in HIV/hepatitis C virus co-infection antiviral therapy.
These two projects study the toxicity of the drug in pregnant HIV infected women and their infants, two populations who are particularly vulnerable to drug-related toxicity. The longitudinal effect of HIV therapy on mtDNA quantity and telomere length in mother and child and the potential effect on mtDNA quality in the children are being investigated.
The HIV/HCV coinfected population is also at higher risk of drug-related adverse events as liver damage cause by both viruses and the drugs add up. We are studying the effect of antiviral drugs on the liver mitochondria in patients undergoing HCV therapy, as well as the effect of therapy on drug metabolism by the liver.
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Mitochondrial toxicity of non-HIV drugs such as statins.
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Acquired mitochondrial disease-like syndromes