DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for methylmalonic acidemia — 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 moduleMethylmalonic acidemia 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 methylmalonic acidemia 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
mevalonate kinase (MVK) — MVK 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2R3V · 2.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2022 Italian case report describes one patient with methylmalonic acidemia who was in a cycle of decompensation and hospitalisation before treatment with carglumic acid (N-carbamylglutamate) was started. Using the lowest effective therapeutic dose of carglumic acid, together with adjustments to the patient’s diet for caloric and protein intake, the authors report that ammonium levels were kept within the normal range and that a normal growth pattern was maintained. The report notes a long follow-up duration and the use of a lower dose in a real-life setting, but it is a single case with no control group.
A 2004 case report from Turkey states that methylmalonic acidemia is a frequent autosomal recessive disorder of organic acid metabolism, and that patients are treated with a diet low in isoleucine, valine, methionine, and threonine, plus supplementation with biotin, cobalamin, and L-carnitine. The same report notes that survival and neurologic outcome are determined by the biochemical response to pharmacological doses of cobalamin and the age of onset of symptoms. It describes a single newborn who presented with poor sucking, vomiting, ketoacidosis, and profound hypotonia from the first day of life.
A 1983 German review describes methylmalonic acidemia as a recessively inherited inborn error of metabolism presenting with metabolic acidosis, vomiting, lethargy, anorexia, and hypotonia. It states that the disease may begin in the neonatal period with acute, life-threatening episodes, or manifest with a milder course and more favourable outcome depending on the location and severity of the enzyme block. The review discusses enzymatic abnormalities, clinical features, diagnostic approach, and possible treatment, and stresses genetic counselling and prenatal diagnosis.
No controlled trials are available. What is missing is any randomised or even systematically controlled evidence for carglumic acid in long-term management of methylmalonic acidemia, as well as any data on patient stratification by enzyme subtype or age of onset that might predict response. Funding for multi-centre trials and standardised outcome measures remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Molecular Genetics & Genomic Medicine · 2022 · 4 citations · open access
Management of methylmalonic acidemia (MMA) with <i>N</i>‐carbamylglutamate: A case report from Italy
AbstractBACKGROUND: Methylmalonic acidemia (MMA) is an inborn error of metabolism whose optimal management, especially in the long-term remains to be established. METHODS: who was in a cycle of episodes of decompensation and hospitalization when we started to use carglumic acid (CA), a well-known adjunctive therapy to standard care for the treatment of acute hyperammonemia due to MMA. RESULTS: Using the lowest effective therapeutic dose of CA and adjusting the patient's diet with caloric and protein intake adequate for her age and pathology, we managed to keep ammonium levels within the normal range, and to ensure a normal growth pattern. CONCLUSION: The present case adds further confirmation of the long-term management of MMA using CA, focusing on the long duration of follow up and on the use of a lower dose of CA in real life settings.
AbstractMethylmalonic acidemia is a recessively inherited inborn error of metabolism presenting with metabolic acidosis, vomiting, lethargy, anorexia, and hypotonia. The disease may either begin in the neonatal period with acute, life-threatening episodes, or manifest itself with a milder clinical course and a more favorable outcome depending on the location and the severity of enzyme block. Enzymatic abnormalities, clinical features, diagnostic approach with regard to differential diagnosis and the possible treatment are discussed. Genetic counseling and prenatal diagnosis are also stressed.
AbstractMethylmalonic acidemia is a frequent, otosomal resessive inherited disorder of organic acid metabolism. In this disorder, the accumulation and excretion of methylmalonic acid and its metabolites are increased. The patients are treated with a diet, low in isoleucin, valin, methionin and treonin and with supplementation of biotin, kobalamine and L-carnitene. The survival and neurologic outcome in methylmalonic acidemia is determined by the biochemical response to pharmacological doses of cobalamine and the age of onset of symptoms. We report a case with methylmalonic acidemia presented with poor sucking, vomitting, ketoacidosis, profound hypotonia beginning from the first day of life with the data from the literature.
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.
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