Mitochondria-targeted peptides in bioenergetic disorders
What randomised evidence supports mitochondria-targeted peptides in primary mitochondrial disease and in age-related functional decline?
§1Abstract
§1.1Review question
What randomised evidence supports mitochondria-targeted peptides in primary mitochondrial disease and in age-related functional decline?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adults with genetically confirmed primary mitochondrial myopathy, and separately, older adults without such a diagnosis. |
| Intervention | Elamipretide or a related mitochondria-targeted tetrapeptide. |
| Comparator | Placebo. |
| Outcomes | Six-minute walk distance; a validated symptom instrument; muscle phosphocreatine recovery kinetics. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 25 August 2024 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.
§1.4Conclusion
Low certainty evidence describes this field. A crossover phase 2 trial in a small sample reported an increase in six-minute walk distance; the subsequent adequately powered phase 3 trial did not meet either of its primary endpoints. The Institute reports the phase 3 result as the more informative of the two and records the sequence as a clear illustration of why a phase 2 estimate in a small crossover sample should not be treated as a confirmatory result. For the second population, no randomised human evidence was identified for any compound in this group.
The conclusion rests on 2 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: Mitochondria-targeted peptides in bioenergetic disorders received 12 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.