DeCure for Mitochondrial DNA depletion syndrome 6 (hepatocerebral type)
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for mitochondrial DNA depletion syndrome 6 (hepatocerebral type) — 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 moduleMitochondrial DNA depletion syndrome 6 (hepatocerebral type) 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 mitochondrial dna depletion syndrome 6 (hepatocerebral type) 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.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Research Square · 2020 · 3 citations · open access
Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: Evaluation of outcomes after liver transplantation
AbstractAbstract Background Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate outcomes LT in MTDPS patients in Japan. Results We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 20 of 23 patients: MPV17 (n=13), DGUOK (n=4), POLG (n=1), MICOS13 (n=1), and TWNK (n=1). Eight MPV17-deficient patients harbored c.451dupC and all four DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n=13, 56.5%). The most frequent liver symptom was cholestasis (n=21, 91.3%). LT was performed on 11 patients, including eight MPV17-deficient and two DGUOK-deficient patients. Four patients, including one with mild intellectual disability, survived; seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G>A or c.293C>T. Conclusions MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, but patients who had MPV17 mutations associated with mild phenotypes such as c.149G>A or c.293C>T and no marked neurologic manifestations before LT, had moderately better outcomes.
Research Square · 2020 · 2 citations · open access
Clinical and molecular basis of hepatocerebral mitochondrial DNA depletion syndrome in Japan: Evaluation of outcomes after liver transplantation
AbstractAbstract Background Hepatocerebral mitochondrial DNA depletion syndrome (MTDPS) is a disease caused by defects in mitochondrial DNA maintenance and leads to liver failure and neurological complications during infancy. Liver transplantation (LT) remains controversial due to poor outcomes associated with extrahepatic symptoms. The purposes of this study were to clarify the current clinical and molecular features of hepatocerebral MTDPS and to evaluate the outcomes of LT in MTDPS patients in Japan. Results We retrospectively assessed the clinical and genetic findings, as well as the clinical courses, of 23 hepatocerebral MTDPS patients from a pool of 999 patients who were diagnosed with mitochondrial diseases between 2007 and 2019. Causative genes were identified in 19 of 23 patients: MPV17 (n = 13), DGUOK (n = 3), POLG (n = 1), and MICOS13 (n = 1). Eight MPV17-deficient patients harbored c.451dupC and all three DGUOK-deficient patients harbored c.143-307_170del335. The most common initial manifestation was failure to thrive (n = 13, 56.5%). The most frequent liver symptom was cholestasis (n = 21, 91.3%). LT was performed on 12 patients, including nine MPV17-deficient and two DGUOK-deficient patients. Among the 12 transplanted patients, five, including one with mild intellectual disability, survived; while seven who had remarkable neurological symptoms before LT died. Five of the MPV17-deficient survivors had either c.149G>A or c.293C>T. Conclusions MPV17 was the most common genetic cause of hepatocerebral MTDPS. The outcome of LT for MTDPS was not favorable, as previously reported, however, patients harboring MPV17 mutations associated with mild phenotypes such as c.149G>A or c.293C>T, and exhibiting no marked neurologic manifestations before LT, had a better prognosis after LT.
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.
