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RARE DISEASE

MELAS

Synonyms: Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes, Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes, Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

Drug discovery

drugs

With orphan designations

Overview

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like Episodes) is a maternally inherited mitochondrial disorder characterized by progressive encephalomyopathy, stroke-like episodes (e.g., hemiparesis, cortical blindness), lactic acidosis, and multiorgan involvement. It arises from mitochondrial DNA mutations, most commonly MT-TL1 (80% of cases). Diagnosis relies on clinical features, neuroimaging showing non-vascular infarcts, elevated lactate, and genetic testing. Management is supportive, focusing on symptom control and preventing metabolic crises [1][5][7].

Population

Affects 1–16/100,000 adults, with typical onset before age 20 (65–76% of cases) [2][5][7].
Represents one of the most common mitochondrial diseases, with equal sex distribution [5][7].

Burden

Progressive neurologic decline, with 40–90% developing dementia and 71–96% epilepsy [2][5].
Median survival ~17 years post-symptom onset; mortality linked to stroke-like events or multisystem failure [7][12].
High healthcare utilization due to recurrent hospitalizations and lifelong multidisciplinary care needs [5][12].

Therapies

Acute care: IV L-arginine for stroke-like episodes; seizure management avoiding valproate [3][7].
Chronic management: Coenzyme Q10, antioxidants, and cochlear implants for hearing loss [7][12].
Multidisciplinary support: Diabetes management, cardiac surveillance, and neurologic rehabilitation [3][7].

Categories: rare cardiac diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare ophthalmic disorders, rare otorhinolaryngological diseases, rare transplant-related disorders

Research Papers

508 drug discovery papers related to MELAS, with 5 first-in-class and 8 next-in-class early-stage therapies forecasted to outperform the average preclinical success rate. Recent publications:

2026-07-02 | Analysis of acute stroke-like lesions in MELAS: Distribution, potential boundaries and spreading pattern.

Imaging during acute episodes of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) primarily shows reversible cortical edema. However, the mechanisms underlying such cortical lesions in MELAS remain unclear. Analyzing MRI findings of MELAS could provide clues to these mechanisms. We reviewed the medical records and imaging data of MELAS patients treated at Peking University First Hospital from 2013 to 2024. 61 MRI scans from 55 patients were included in this study. The spatial distribution of SLLs was analyzed based on high-resolution cortical segmentation. Next, we established a non-negative independent component analysis (nnICA) model to separate independent SLL components. Then we assessed correlation of synaptic density and lesion load using Spearman's rho test. Finally, a simple diffusion model was used to fit the spreading behavior of SLLs. The cortical probability map shows a peak involvement frequency of 0.46 observed in the left temporo-occipital lobe. Distribution of SLLs showed no bias between left and right hemisphere. Then we identified 8 independent cortical components of SLLs. The Probability Map showed a positive correlation with synaptic density map (Spearman's rho = 0.32, p < 0.001). Additionally, the Directed-Effect Coefficient exhibited a good proportional relationship with the Dilation Coefficient (y = 0.50x+0.00, r = 0.76). Analysis of structural MRI data suggests that MELAS SLLs exhibit a pattern of free spreading within regions and restricted spreading between regions on the cortex. The identified components indicate the presence of potential boundaries. We also showed that lesion spreading was often hindered in areas with sparse synaptic density.

Open article ↗

2026-06-20 | Generation of a patient-derived iPSC line from a clinically diagnosed MELAS case carrying the mtDNA m.3243A > G variant.

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes) represents a multisystemic mitochondrial disease mainly triggered by heteroplasmic m.3243A > G mutation in mtDNA MT-TL1, the gene for tRNA^Leu(UUR). Here we report the successful reprogramming of peripheral blood mononuclear cells (PBMCs) from a female MELAS patient into induced pluripotent stem cells (iPSCs). This patient-specific iPSC line provides a valuable platform to investigate MELAS pathophysiology and screen therapeutic interventions targeting mitochondrial dysfunction in a genetically relevant context.

Open article ↗

2026-07-02 | Analysis of acute stroke-like lesions in MELAS: Distribution, potential boundaries and spreading pattern.

Open article ↗

2026-06-20 | Generation of a patient-derived iPSC line from a clinically diagnosed MELAS case carrying the mtDNA m.3243A > G variant.

Open article ↗

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Drug Discovery Landscape

7 orphan drug designations for MELAS.

Drug	Therapy type	Regulator	Orphan designation	Approval	Sponsor
Vatiquinone	small molecules	EMA	2022-02-24	—	PTC Therapeutics International Limited
Mavodelpar sodium	small molecules	EMA	2020-08-21	—	Scendea (NL) B.V.
2-isopropyl-3H-naphtho[1,2-d]imidazole-4,5-dione	small molecules	EMA	2017-12-12	—	Pharming Technologies B.V.
nicotinamide riboside	small molecules	FDA	2017-01-25	—	Rejuvenation Therapeutics
Sonlicromanol hydrochloride [KH176]	small molecules	EMA	2015-08-10	—	Khondrion B.V.
idebenone	small molecules	FDA	2009-05-22	—	Santhera Pharmaceuticals (Switzerland) Ltd.
5-[(E)-2-(4-hydroxyphenyl)-ethenyl] benzene-1,3 diol	small molecules	FDA	2008-03-13	—	Sirtris Pharmaceuticals, Inc.

MELAS

MELAS

MELAS

Overview

Population

Burden

Therapies

Categories: rare cardiac diseases, rare developmental anomalies during embryogenesis, rare genetic diseases, rare inborn errors of metabolism, rare neurological diseases, rare ophthalmic disorders, rare otorhinolaryngological diseases, rare transplant-related disorders

Research Papers

2026-07-02 | Analysis of acute stroke-like lesions in MELAS: Distribution, potential boundaries and spreading pattern.

2026-06-20 | Generation of a patient-derived iPSC line from a clinically diagnosed MELAS case carrying the mtDNA m.3243A > G variant.

2026-07-02 | Analysis of acute stroke-like lesions in MELAS: Distribution, potential boundaries and spreading pattern.

2026-06-20 | Generation of a patient-derived iPSC line from a clinically diagnosed MELAS case carrying the mtDNA m.3243A > G variant.

Drug Discovery Landscape

Updated: Jul 29, 2026