ReviewTherapeutic advances in rare disease
2000-2025: Emerging therapies in primary mitochondrial disease: A structured review, horizon scan, and roadmap for the future.
Review in Therapeutic advances in rare disease. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
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Authors and funding
9 authors.
Funding
Abstract
Primary mitochondrial diseases (PMD) are ultra-rare, genetically diverse disorders that impair cellular energy metabolism and typically present with multisystemic symptoms. Over the past decades, the therapeutic landscape of PMD has evolved substantially. Early trials of non-specific antioxidant and metabolic therapies produced largely negative or mixed results, providing important methodological lessons for the field. More recent studies have adopted improved outcome measures, natural history-informed designs, and precision therapeutic approaches, including gene therapy and nucleoside therapy, which have shown encouraging clinical and regulatory progress. Regulatory agencies have only recently begun approving disease-modifying therapies for selected mitochondrial disorders. The European Medicines Agency (EMA) approved idebenone for Leber Hereditary Optic Neuropathy (LHON) in 2015 but only recently, in 2025 did the Food and Drug Administration (FDA) in the US approve a treatment for Barth syndrome and thymidine kinase 2 deficiency (TK2d). Friedreich's ataxia received regulatory approval in 2023 from both the EMA and FDA, marking another milestone in mitochondria-related disorders. To comprehensively review clinical and regulatory developments in PMD over the past two decades, we conducted a structured scoping review and horizon scan of published clinical trials and regulatory approvals in PMD from January 2000 to November 2025. Data sources included PubMed, Embase, https://ClinicalTrials.gov, and regulatory agency websites. Recent accelerated and full FDA approvals validate the feasibility of tailored evidence packages, but sustaining this momentum will require more rigorous alignment of trial design with molecular biology, strengthening of natural history infrastructure, deployment of sensitive biomarkers, and adoption of innovative statistical approaches. Early regulatory engagement and robust patient-community partnerships will be key.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.