Reducing NADH-related stress in mitochondrial disease

Targeting NADH-Reductive Stress in Mitochondrial Disease

NIH-funded research Emory University · NIH-11332292

An injected engineered enzyme called LOXCAT aims to lower a harmful NADH-related imbalance in people with inherited mitochondrial disorders like Leigh syndrome.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionEmory University NIH-funded
Lab location1 site (Atlanta, United States)
Project IDNIH-11332292 on NIH RePORTER

What this research studies

Mitochondrial diseases can raise the NADH/NAD+ ratio and block many vital biochemical reactions, causing muscle and brain problems. Researchers engineered a fusion enzyme, LOXCAT, that converts lactate into pyruvate to lower NADH-driven stress across tissues. They have given LOXCAT by IV in mice and are using animal models, biochemical measurements, and blood lactate/pyruvate testing to refine the approach and track effects on organs. The work is focused on creating a therapy that could reach multiple affected tissues in people with electron transport chain defects.

Who could benefit from this research

Good fit: People with diagnosed inherited mitochondrial ETC disorders (for example Leigh syndrome) and evidence of elevated lactate/pyruvate or related metabolic imbalance.

Not a fit: People whose symptoms come from non-ETC causes or whose disease has progressed to irreversible organ failure are less likely to benefit.

Why it matters

Potential benefit: If successful, this approach could reduce tissue damage and symptoms and offer a novel therapy for some inherited mitochondrial electron transport chain disorders.

How similar studies have performed: This LOXCAT approach is novel: early animal studies have shown it can lower blood lactate/pyruvate and NADH, but it has not yet been tested in people.

Where this research is happening

Atlanta, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.