Mitochondria at the center.

The Problem

Mitochondrial failure is a primary driver of muscle degeneration in chronic disease and aging, and contributes more broadly to age-related muscle loss and systemic decline. When energy production falters, muscle tissue weakens, regeneration slows, and functional capacity deteriorates. There are limited therapies that directly restore cellular energy in compromised muscle.

Approach

This project advances mitochondrial transplantation — a pioneering therapeutic strategy that restores cellular energy by delivering healthy mitochondria directly into damaged muscle tissue. Isolated healthy mitochondria are injected into compromised muscle, where they integrate into host cells and reestablish energy production, metabolic signaling, and cellular resilience. Dr. McCully’s laboratory has demonstrated safety and functional benefit in both cardiac and skeletal muscle, including clinical application in pediatric cardiac patients. Countdown funding now extends this work into a validated Duchenne Muscular Dystrophy (DMD) genetic mouse model, with potential to improve muscle cell survival, reduce inflammation, strengthen cardiac performance, and slow disease progression.

Progress

Newly awarded in February 2026, this project builds on established safety data and translational groundwork. The current phase evaluates therapeutic impact in a muscular disease model, positioning the approach for broader clinical development.

Strategic Relevance

Mitochondrial transplantation represents direct restoration of cellular energy at its source. Anchored in muscular disease, this strategy also carries significant translational potential for aging-related muscle decline and other chronic conditions characterized by mitochondrial failure — including cardiomyopathies, age-related sarcopenia, cachexia, and neuromuscular disorders — reinforcing Countdown’s commitment to frontier therapies with broad-reaching impact.

The Problem

Damaged mitochondria accumulate in neurodegeneration, primary mitochondrial disorders, and aging. When cellular clearance pathways fail, dysfunctional mitochondria persist, contributing to neuronal injury and progressive decline. For years, scientists have known something remarkable: when the body is deprived of oxygen, cells activate a powerful self-repair program. In people with Parkinson’s, rare mitochondrial diseases, and a wide range of chronic conditions, this kind of cellular renewal could be transformative — the problem is getting there safely.

Approach

Dr. Adriaenssens works on a molecular complex that acts as a brake on one of the cell’s mitochondrial clearance pathways — one that is activated by hypoxia. By studying this complex, the team aims to identify the precise molecular targets needed to release that brake selectively, activating mitochondrial renewal without any systemic oxygen deprivation. Because sustained low oxygen is not a safe or practical therapy, the objective is to isolate the precise mitochondrial pathways responsible for these benefits and define their molecular ‘on-off’ mechanisms — therapeutically mimicking the protective effects of hypoxia without reducing oxygen levels.

Progress

Newly awarded in February 2026. Updates will be shared as the research progresses.

Strategic Relevance

By identifying molecular switches that safely activate beneficial stress-response pathways, this work could enable therapies that restore mitochondrial health across primary mitochondrial disease, neurodegeneration, cancer, and aging — without the systemic risks of hypoxia itself.

The Problem

Despite mitochondria serving as the cell’s primary energy system, mitochondrial performance is rarely quantified in routine clinical care. There are no standardized, widely accepted tools to measure mitochondrial function, quality, or content in blood — limiting early diagnosis, disease tracking, and therapeutic evaluation.

Approach

This project is developing standardized, blood-based mitochondrial scoring tools capable of measuring mitochondrial function, quality, and content. Using a defined biomarker panel, the team generates ‘MitoScores’ designed to distinguish health from disease and establish reference ranges that can support clinical decision-making. The long-term vision is to integrate mitochondrial assessment into routine checkups — transforming mitochondrial health into a measurable, actionable diagnostic category.

Progress

Minovia has opened its mitochondrial biomarker clinical trial at Sheba Medical Center. The study is enrolling patients with primary mitochondrial disease alongside healthy volunteers, and blood samples are actively being processed in Haifa laboratories. MitoScores are being generated to define reference ranges that distinguish dysfunction from health. In parallel, Minovia’s lead investigational therapy, MNV-201, received FDA Fast Track and Orphan Drug Designations in myelodysplastic syndrome, reinforcing regulatory momentum around its mitochondrial platform. The company has also secured two new U.S. patents supporting its Mitochondrial Augmentation Therapy (MAT) platform.

Strategic Relevance

Measurement infrastructure is foundational to therapeutic progress. By standardizing mitochondrial biomarkers, this project provides the diagnostic backbone for the broader mitochondrial ecosystem — enabling earlier detection, better patient stratification, and more precise evaluation of emerging therapies. It positions mitochondrial scoring to evolve from a research tool into a routine clinical diagnostic with potential to become a household measure of cellular health.

The Problem

The electron transport chain (ETC) produces most of the cell’s ATP. In mitochondrial disease, inherited ETC mutations disrupt electron flow, causing toxic electron accumulation (NADH-reductive stress) and energy failure in high-demand organs such as the brain and heart. There are currently no FDA-approved therapies that broadly address this core biochemical dysfunction. Similar electron transport disruptions are also implicated in cancer metabolism and neurodegenerative diseases such as Parkinson’s.

Approach

Dr. Patgiri’s team engineered a first-in-class therapeutic protein called LOXCAT, designed to safely reroute excess electrons when mitochondrial energy production is impaired. When administered into the bloodstream, LOXCAT transfers excess electrons from circulating metabolites to oxygen, reducing toxic buildup across multiple organs. In effect, it functions as an artificial electron transport pathway in the blood — restoring redox balance and supporting cellular metabolism systemically. While strategically positioned to address primary mitochondrial disease, LOXCAT has also been tested in models relevant to cancer and Parkinson’s, demonstrating broader translational potential.

Progress

In preclinical studies, LOXCAT reduced toxic electron accumulation in the brain and heart of mitochondrial disease models. The team is now improving the protein’s durability in circulation and developing a gene-therapy version that could enable long-term therapeutic benefit from a single treatment.

Strategic Relevance

LOXCAT targets a shared biochemical consequence across multiple mitochondrial mutations: excess electron buildup. By anchoring in rare mitochondrial disease while addressing a mechanism relevant to cancer, neurodegeneration, and aging, this project reflects Countdown’s two-lens strategy — funding rare disease breakthroughs with broad systemic impact.

The Problem

Inherited mitochondrial disorders caused by single-gene mutations require highly precise gene correction strategies. In MEPAN syndrome, mutations in the MECR gene disrupt mitochondrial lipid metabolism, leading to progressive neurological impairment. There are currently no approved disease-modifying therapies for this condition.

Approach

This project advances a viral gene replacement strategy designed to restore functional MECR expression in validated disease models. Using an optimized viral vector platform, the therapy delivers a healthy copy of the MECR gene to affected tissues, with a focus on targeting neurological involvement.

Progress

Phase I development has been completed. The team achieved robust gene expression in the brain and has advanced into efficacy studies to evaluate functional and clinical impact in disease models. Emerging findings reveal that mitochondrial lipid pathways disrupted in this rare disorder are also altered in Alzheimer’s disease — suggesting a shared mitochondrial mechanism that extends beyond rare disease.

Strategic Relevance

Anchored in a rare single-gene disorder, this work establishes a precision gene-replacement template for primary mitochondrial disease while opening new translational pathways into Alzheimer’s and other conditions shaped by mitochondrial lipid metabolism.