Richard Festenstein explored the intersection of genetics, clinical innovation, and technology in the context of rare neurological diseases. He began by recounting the journey that led to the use of motion capture suits, originally developed for the film industry, to study patient behaviour in clinical settings. Festenstein highlighted Friedreich’s ataxia, the most common inherited ataxia, which typically results in wheelchair use by the age of 35 and premature death due to cardiomyopathy. He explained that the severity of the disease is linked to the number of triplet repeat expansions in the affected gene.
Festenstein traced the origins of epigenetic inheritance to early experiments with fruit flies, where chromosomal changes led to gene silencing and the concept of the histone code. He drew parallels between these foundational discoveries and the mechanism of gene silencing in Friedreich’s ataxia, where triplet repeats induce a heterochromatin state that silences the gene. This understanding has opened avenues for therapeutic intervention, with epigenetic modifiers now being investigated as potential treatments to reactivate the silenced gene.
The presentation described a pilot clinical trial using nicotinamide, which demonstrated persistent upregulation of the repressed protein in patients. Festenstein emphasised the limitations of traditional clinical scales, which often fail to capture the full spectrum of patient experience. To address this, he and his collaborators introduced motion capture technology, enabling objective measurement of movement and progression. This innovation has led to the development of predictive algorithms that can accurately assess disease severity and even predict biomarker levels from movement data.
Festenstein’s ongoing work extends beyond Friedreich’s ataxia to other conditions such as Duchenne muscular dystrophy. The team has patented key features derived from motion data, which allow for smaller and shorter clinical trials – an especially important advancement for rare diseases. The concept of “ethomics”, or the measurement of behaviour, is now being applied to a range of movement disorders, including arthritis, dementia, and Parkinson’s disease. By integrating real-world data and machine learning, Festenstein’s research is accelerating clinical trials and enhancing the precision of outcome measurement, promising significant improvements in patient care and drug development.
