Project overview

Primary mitochondrial diseases impact lifespan and quality of life and are multisystem disorders that typically manifest in childhood. These are mostly a result of maternally inherited mitochondrial DNA (mtDNA), which often coexist with healthy mtDNA within cells (heteroplasmy). Defective mtDNA and energy production impairment determines the clinical manifestations, which in these cases are highly variable.

There is currently no cure for these diseases, and treatment focuses only on easing symptoms. Getting an early and accurate diagnosis is crucial, but it remains difficult to achieve. Traditional methods, such as muscle biopsies, are invasive, provide only a localised snapshot of disease, and are unsuitable for repeated monitoring. Moreover, assessing mtDNA mutations in blood cells often underestimates the mutant load in highly energy-demanding tissues, such as the heart, which frequently harbour higher levels of pathogenic variants.

MITEST proposes the development of a point-of-care (PoC) diagnostic test based on circulating cell-free mitochondrial DNA (ccf-mtDNA). ccf-mtDNA reflects mitochondrial dysfunction and cellular stress, offering a dynamic measure of disease progression and treatment response. Importantly, quantifying mtDNA levels and heteroplasmy in small volumes of body fluids offers a minimally invasive approach to enable early diagnosis, refine patient stratification, and facilitate longitudinal monitoring of disease dynamics.

This project brings together ICN2’s expertise in point-of-care diagnostic test development and IRB’s knowledge in mitochondrial DNA. The development of a PoC ccf-mtDNA test is a significant step toward precision medicine in mitochondrial disease, bringing accurate diagnosis and monitoring to the point of need.