Longitudinal Evaluation of Brain and Cardiac Mitochondrial Complex 1 Expression in Patients with Friedreich’s Ataxia

Exploring PET and MRI biomarkers to assess mitochondrial dysfunction and inform CNS clinical trial development.

The development of disease-modifying therapies for Friedreich’s Ataxia (FA) is challenged by the limited availability of objective biomarkers capable of measuring disease progression and treatment response. Advanced molecular imaging offers an opportunity to better characterize mitochondrial dysfunction and generate quantitative evidence to inform clinical development.

In this study, researchers from Perceptive Discovery, Imperial College London and Takeda Pharmaceuticals evaluated longitudinal changes in mitochondrial complex I (MC1) expression in the brain and heart of patients with Friedreich’s Ataxia. Using [¹⁸F]BCPP-EF PET imaging alongside advanced MRI techniques, the study assessed changes in mitochondrial function and brain microstructure over approximately 12 months.

The findings confirmed significantly reduced cardiac MC1 expression in patients compared with healthy volunteers, alongside differences in regional brain microstructure. Although no significant longitudinal changes were observed over the study period, the results provide valuable insights into imaging biomarker sensitivity, disease characterization and sample size considerations for future clinical trials.

What You’ll Learn:

• Quantifying mitochondrial dysfunction: How [¹⁸F]BCPP-EF PET imaging can assess MC1 expression in the brain and heart of patients with Friedreich’s Ataxia.
• Evaluating imaging biomarkers: Key findings from longitudinal PET and MRI assessments, including differences in cardiac MC1 expression and brain microstructure.
• Informing CNS clinical trial design: How quantitative imaging data can support biomarker selection, sample size estimation and the development of future disease-modifying therapy trials.