C4*
Novel Treatment of Diseases Associated with or Caused by Mitochondrial Dysfunction
Dr Jaya Krishnan, Goethe University Frankfurt; Dr Arka Provo Das, Goethe University Frankfurt
Innovectis
Challenge
Mitochondrial dysfunction is one of the most pervasive and least tractable drivers of human disease. It underlies a vast spectrum of conditions, from rare genetic mitochondrial syndromes to common disorders of aging, cardiomyopathy, neurodegeneration, and metabolic decline. Yet despite decades of research, mitochondrial medicine remains largely symptomatic: most interventions fail to address the core biological problem — the progressive accumulation of dysfunctional mitochondria in post-mitotic tissues such as the heart, brain, and skeletal muscle. A central barrier has been the lack of predictive human models capable of capturing mitochondrial disease in a physiologically relevant, multicellular tissue context. Kearns–Sayre syndrome (KSS) exemplifies this challenge. It is a devastating mitochondrial disorder caused by large-scale mtDNA deletions, with cardiac dysfunction as the primary cause of mortality. Disease progression is driven not only by genetic lesions, but by the expansion of mutant mitochondrial populations over time — a dynamic process that conventional approaches cannot effectively reverse.
Technology
We are developing a first-in-class mitochondrial therapeutic platform based on a dual-action principle: selective elimination of dysfunctional mitochondria coupled with regeneration of healthy mitochondrial populations. Our approach integrates two core mechanisms: a) Mitophagy enhancement and b) Metabolic and mitochondrial reprogramming. This dual-action strategy enables mitochondrial “population correction”: rather than attempting to repair individual mutations. Using this approach, we identified Betaxolol, an FDA-approved β1-selective antagonist, as a potent modulator of mitochondrial quality control. Mechanistically, Betaxolol increases intracellular oxygenation, selectively triggers mitophagy of dysfunctional mitochondria, and promotes biogenesis of functional organelles — restoring contractility in diseased cardiac tissue. This represents a new therapeutic paradigm: mutation-agnostic mitochondrial regeneration through organelle-level competition, with broad relevance across mitochondrial disorders, cardiac disease, and age-associated decline.
Commercial Opportunity
Mitochondrial dysfunction represents one of the largest untapped therapeutic markets in modern medicine, spanning both rare genetic syndromes and high-prevalence chronic diseases. We are initially focused on Kearns–Sayre syndrome, a severe rare disorder with clear genetic causality, high cardiac mortality, and no disease-modifying therapies. This provides an accelerated regulatory and clinical entry point with strong unmet need and orphan-drug potential. However, the commercial horizon extends far beyond KSS. The same mitochondrial quality-control failure drives pathology across: • cardiomyopathies and heart failure • neurodegenerative diseases (Parkinson’s, Alzheimer’s) • metabolic syndromes • inflammatory aging and frailty • longevity-associated organ decline.
Development Status
We have established a robust scientific and translational foundation, supported by both platform validation and therapeutic proof-of-concept:
1. Human organoid (cardiomorph) platform and first human 3D cardiac model of KSS established
2. Therapeutic discovery and validation of Betaxolol and Nadolol as model and lead modulators showing
3. Pipeline and expansion strategy toward broader mitochondrial and age-related indications.
4. Financing and next milestones with the aim of preparing a $10-15M Series A.
Patent Situation
EP priority patent application no. EP25176527, filed in Oct. 2025
Further Reading
doi.org/10.64898/2025.12.18.695153
