DeCure for Multiple mitochondrial dysfunctions syndrome 4
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for multiple mitochondrial dysfunctions syndrome 4 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMultiple mitochondrial dysfunctions syndrome 4 maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for multiple mitochondrial dysfunctions syndrome 4 is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
NPC intracellular cholesterol transporter 2 (NPC2) — NPC2 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet c3sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5KWY · 2.405 Å · ligand CHOLEST-5-EN-3-YL HYDROGEN SULFATE (C3S). Experimental structure, not a prediction.
What the evidence adds up to
No abstract in this set reports a clinical trial or any patient outcome for multiple mitochondrial dysfunctions syndrome 4 specifically. The 2015 systematic review states that no curative therapy is available for mitochondrial diseases as a group and that previous clinical trials have been poorly designed, showing some evidence of enhanced mitochondrial function but without significant results. The 2016 letter notes that for the majority of classical mitochondrial syndromes, current therapeutic options are limited to supportive care, though a small number of defects in cofactor metabolism are amendable by specific treatment strategies; multiple mitochondrial dysfunctions syndrome 4 is not listed among those treatable defects. The 2020 review repeats that no disease-modifying therapy exists and that management relies on supportive and symptomatic care, avoidance of catabolic stressors, and careful use of drugs for comorbidities.
The 2014 and 2023 reviews discuss mitochondrial dysfunction in psychiatric disorders and in complex diseases generally, but neither addresses any drug or intervention for multiple mitochondrial dysfunctions syndrome 4. No abstract provides a sample size, survival rate, or response rate for any compound in this disease. The 2015 review mentions that several compounds under investigation have poor pharmacokinetic profiles or numerous off-target effects, and that drug development teams should continue screening compound libraries, but this remains a general statement about the field, not a finding for this specific syndrome.
What is still missing: any clinical trial data for multiple mitochondrial dysfunctions syndrome 4, any patient-stratified study, and any dedicated funding for a trial in this ultra-rare disorder. Without a specific biochemical defect that is known to be druggable in this syndrome, the path from general mitochondrial research to a treatment for this patient group remains undefined.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brazilian Journal of Psychiatry · 2014 · 82 citations · open access
Mitochondria and the central nervous system: searching for a pathophysiological basis of psychiatric disorders
AbstractINTRODUCTION: Mitochondrial dysfunction has been postulated to participate in the development of many neuropsychiatric disorders, but there is no consensus as to its role. The aim of this paper is to review recent studies and to outline the current understanding of the association between mitochondrial dysfunction and psychiatric disorders. METHODOLOGY: We reviewed articles that evaluated mitochondrial dysfunction and psychiatric disorders, with a particular focus on depression, bipolar disorder, anxiety disorders, obsessive-compulsive disorder, and autism spectrum disorder, and the association between mitochondrial dysfunction and development of these disorders. RESULTS: Evidence suggests that alterations in mitochondrial morphology, brain energy metabolism, and mitochondrial enzyme activity may be involved in the pathophysiology of different neuropsychiatric disorders, given their key role in energy metabolism in the cell. CONCLUSIONS: Understanding the interactions between mitochondrial dysfunction and development of psychiatric disorders may help establish more effective therapeutic strategies for these disorders and thus lead to better outcomes for affected subjects.
Treatable mitochondrial diseases: cofactor metabolism and beyond
AbstractSir,
In the past, numerous articles related to disorders of mitochondrial cofactor metabolism have been published in Brain (Ozand et al. , 1998; Gempel et al. , 2007; Johnson et al. , 2012; Foley et al. , 2014; Haack et al. , 2014; Ortigoza-Escobar et al. , 2016). These studies not only facilitated our understanding of the underlying biochemical defects, but also paved the way to specific treatment options. As a consequence our clinical view on mitochondrial diseases has changed substantially during the last years.
The umbrella term ‘mitochondrial disease’ comprises a large group of inherited metabolic disorders caused by dysfunction of the pyruvate oxidation route. Our common understanding of mitochondrial diseases mainly refers to classical mitochondrial syndromes such as Leigh syndrome or MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). However, the spectrum of mitochondrial diseases is much broader and the development of novel genetic tools has undeniably advanced our knowledge about this disease group. During the past 6 years more than 100 novel mitochondrial diseases have been identified via next generation sequencing (NGS) strategies leading to a total number of around 280 known disease genes, affecting diverse mitochondrial pathways. Accordingly, clinical management of affected individuals is challenging and diagnostic strategies are in flux.
Unfortunately, current therapeutic options for the majority of classical mitochondrial syndromes are limited to supportive care. Nevertheless, apart from these prognostically unfavourable diseases, there are several mitochondrial defects that are amendable by specific treatment strategies (Table 1). Among the group of these ‘treatable mitochondrial diseases’, defects of cofactor metabolism play a major role.
View this table:
Table 1
Inherited mitochondrial diseases with specific treatment options
For …
British Medical Bulletin · 2015 · 26 citations · open access
Potential compounds for the treatment of mitochondrial disease
AbstractINTRODUCTION: Mitochondrial diseases are a group of heterogeneous disorders for which no curative therapy is currently available. Several drugs are currently being pursued as candidates to correct the underlying biochemistry that causes mitochondrial dysfunction. SOURCES OF DATA: A systematic review of pharmacological therapeutics tested using in vitro, in vivo models and clinical trials. Results presented from database searches undertaken to ascertain compounds currently being pioneered to treat mitochondrial disease. AREAS OF AGREEMENT: Previous clinical research has been hindered by poorly designed trials that have shown some evidence in enhancing mitochondrial function but without significant results. AREAS OF CONTROVERSY: Several compounds under investigation display poor pharmacokinetic profiles or numerous off target effects. GROWING POINTS: Drug development teams should continue to screen existing and novel compound libraries for therapeutics that can enhance mitochondrial function. Therapies for mitochondrial disorders could hold potential cures for a myriad of other ailments associated with mitochondrial dysfunction such as neurodegenerative diseases.
Scientific Reports · 2023 · 20 citations · open access
Recent advances and new perspectives in mitochondrial dysfunction
AbstractIn the last decade, there has been an increased appreciation for mitochondria as central hubs in diverse processes, such as cellular energy, immunity, and signal transduction. As such, we have become aware that mitochondrial dysfunction underlies many diseases, including primary (mutations in genes encoding mitochondrial proteins) and secondary mitochondrial diseases (mutations in non-mitochondrial genes critical for mitochondrial biology), as well as complex diseases with mitochondrial dysfunction (chronic or degenerative diseases). Evidence suggests that mitochondrial dysfunction may often precede other pathological signs in these disorders, further modulated by genetics, environment, and lifestyle.
Journal of Clinical Medicine · 2020 · 14 citations · open access
Therapeutical Management and Drug Safety in Mitochondrial Diseases—Update 2020
AbstractMitochondrial diseases (MDs) are a group of genetic disorders that may manifest with vast clinical heterogeneity in childhood or adulthood. These diseases are characterized by dysfunctional mitochondria and oxidative phosphorylation deficiency. Patients are usually treated with supportive and symptomatic therapies due to the absence of a specific disease-modifying therapy. Management of patients with MDs is based on different therapeutical strategies, particularly the early treatment of organ-specific complications and the avoidance of catabolic stressors or toxic medication. In this review, we discuss the therapeutic management of MDs, supported by a revision of the literature, and provide an overview of the drugs that should be either avoided or carefully used both for the specific treatment of MDs and for the management of comorbidities these subjects may manifest. We finally discuss the latest therapies approved for the management of MDs and some ongoing clinical trials.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
