Mitochonic Acid 5

MA-5 was identified by screening indole-3-acetic-acid derivatives for increased cellular ATP. Its 2015 discovery paper tested cells from patients with Leigh syndrome, MELAS, Leber hereditary optic neuropathy and Kearns–Sayre syndrome [3].

A 2017 study found protection against experimentally induced oxidative stress in fibroblasts from 24 of 25 patients. The remaining cell line resisted the stressor itself, so the rescue assay could not assess benefit there. These were cultured cells, not 25 people treated with MA-5 [4].

Animal and disease-model findings

• In a 2026 mitochondrial DNA deletion study, seven symptomatic mice received MA-5 and seven received vehicle. Kidney findings included lower creatinine and improved tissue structure. Resting lactate did not differ significantly between disease groups; the lactate benefit appeared after glucose loading. Cardiac respiratory histochemistry also showed no significant between-group difference [5].
• A 2025 Barth syndrome study found improved ATP production and mitochondrial morphology in patient-derived cells, and improved movement and heart rate in flies. The abnormal monolysocardiolipin/cardiolipin ratio was unchanged [6].
• A September 2026 ALS study reported improved movement and survival in flies and ATP production in patient-derived motor neurons. Its exploratory mouse comparison had only one animal per group and could not support statistical inference [7].

Clinical development

The evidence tier reflects completed phase I testing, not demonstrated treatment efficacy [2]. As checked on 1 October 2026, phase II trial jRCT2031250505 is listed as recruiting 15 people with mitochondrial disease and hearing loss. The blinded, placebo-controlled protocol lasts 12 weeks and measures hearing, disease markers and safety; it has no posted efficacy results [8].

Mitofilin/MIC60 helps organise cristae, the folds of the inner mitochondrial membrane. MA-5 binding was supported by affinity purification and binding assays, with assay-dependent affinity estimates. These experiments support a target hypothesis rather than demonstrating human target engagement [1].

MA-5 promoted ATP synthase oligomerisation and larger protein complexes in the 2017 experiments. The proposed mechanism is more efficient ATP production through local membrane organisation. In the tested fibroblasts, ATP increased without a corresponding rise in oxygen consumption or a change in whole-mitochondrial membrane potential [4].

Reduced oxidative stress in some models should not be interpreted as universal direct radical scavenging. The discovery study found no reduction in cellular ROS in its peroxide-stress experiment and no replenishment of glutathione [3].

A 2026 biochemical study also found reversible, non-competitive inhibition of the carnitine/acylcarnitine carrier. Reported IC50 values were approximately 73 µM for native rat protein and 58 µM for recombinant protein. These are isolated transport assays, not evidence of clinical fat loss or a demonstrated drug interaction [9].

Among 58 healthy men, including placebo recipients, phase I reported seven with grade 1 adverse events, no drug-attributed reactions, serious events or discontinuations. Event types are undisclosed. These registry results do not establish long-term safety [2].

The 2025 hearing-loss experiment found a dose-dependent adverse signal. At 2 mg/kg/day, several hearing measures improved. At 4 mg/kg/day, outer hair-cell loss increased and otoacoustic emissions worsened at some frequencies. This small mouse study does not define a human toxicity threshold [10].

The 2026 ALS paper likewise reported a limited concentration window: 100 nM improved ATP in motor neurons, while 10 µM or more appeared ineffective or potentially harmful. Sporadic-ALS fibroblasts also showed less benefit or possible harm at 30 µM [7].

Clinical combination safety has not been established by the cited MA-5 studies. The carrier inhibition result is a biochemical finding and does not demonstrate an interaction with carnitine supplements [9].