DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for methylmalonic aciduria, cblB 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 moduleMethylmalonic aciduria, cblB 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 methylmalonic aciduria, cblb 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.
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
The abstracts provided do not address methylmalonic aciduria, cblB type. The 2006 study of 77 Chinese patients with methylmalonic aciduria found that 40.3% had isolated methylmalonic aciduria and 59.7% had the combined form with homocystinemia. Neonatal and infantile onset was associated with greater severity. Among 17 patients with onset after 3 years, 16 had the combined form; 9 of those with combined disease completely recovered with normal intelligence, and 7 improved with a mild handicap. No specific drug treatment is reported in that study.
The 2022 study on late-onset cblC deficiency (the most common type of methylmalonic aciduria in China) included 56 patients aged 10 to 20 years. After metabolic treatment with cobalamin, l-carnitine, and betaine, all patients showed improvement, and 30 school-aged patients returned to school. Two female patients had healthy babies. Neuropsychiatric disease occurred in 82.1% of patients, cardiovascular disease in 19.6%, pulmonary hypertension in 10.7%, and renal damage in 10.7%. The study does not report survival rates or response rates as concrete numbers beyond stating all patients improved.
No abstract in the set provides data on cblB type specifically. The 2022 study concerns cblC deficiency, a different genetic subtype. The 2006 study does not specify cblB type among its patients. There are no controlled trials, no randomised comparisons, and no long-term outcome data beyond the reported improvements. What is missing is any direct evidence for cblB type, any randomised trial design, any stratification by genetic subtype, and any funding for dedicated studies of cblB patients.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Child Neurology · 2006 · 18 citations
Clinical and Biochemical Studies on Chinese Patients With Methylmalonic Aciduria
AbstractMethylmalonic aciduria is a common organic aciduria disease. Recently, gas chromatography-mass spectrometry has been used to diagnose methylmalonic aciduria in China. Often, however, the diagnosis of methylmalonic aciduria is delayed because of a lack of technical expertise and the limited experience of general clinicians in China. In this study, the natural history, clinical features, and outcome of 77 Chinese patients with methylmalonic aciduria were investigated. Of the 77 patients, 31 (40.3%) had isolated methylmalonic aciduria and 46 (59.7%) had methylmalonic aciduria combined with homocystinemia. Thus, we observed a higher rate of the combined disease than studies conducted in other countries, suggesting that it might be more common in China. Total plasma homocysteine measurement might enable differential diagnoses of methylmalonic aciduria to be distinguished. The clinical spectrum of these 77 patients with methylmalonic aciduria ranged from neonatal death and severe symptoms to benign asymptomatic organic aciduria. Neonatal and infantile onset, which was a characteristic of the majority of cases, was associated with a greater severity relative to later-onset cases. Among the 17 cases who had onset after 3 years of age, only 1 patient had isolated methylmalonic aciduria and 16 had combined methylmalonic aciduria and homocystinemia. Nine of the patients with combined methylmalonic aciduria and homocystinemia completely recovered and exhibited normal intelligence, whereas seven improved, with a mild handicap.
Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment
AbstractAbstract Background cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty. Results This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, l-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies. Conclusions Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, l-carnitine, and betaine appears to be beneficial.
Late-onset cblC deficiency around puberty: a retrospective study of the clinical characteristics, diagnosis, and treatment
AbstractAbstract Background cblC deficiency is the most common type of methylmalonic aciduria in China. Late-onset patients present with various non-specific symptoms and are usually misdiagnosed. The purpose of this study is to investigate the clinical features of patients with late-onset cblC deficiency and explore diagnosis and management strategies around puberty. Results This study included 56 patients (35 males and 21 females) with late-onset cblC deficiency who were admitted to our clinic between 2002 and September 2021. The diagnosis was confirmed by metabolic and genetic tests. The clinical and biochemical features, disease triggers, outcome, and associated genetic variants were examined. The onset age ranged from 10 to 20 years (median age, 12 years). Fifteen patients (26.8%) presented with symptoms after infection or sports training. Further, 46 patients (82.1%) had neuropsychiatric diseases; 11 patients (19.6%), cardiovascular diseases; and 6 patients (10.7%), pulmonary hypertension. Renal damage was observed in 6 cases (10.7%). Genetic analysis revealed 21 variants of the MMACHC gene in the 56 patients. The top five common variants detected in 112 alleles were c.482G > A (36.6%), c.609G > A (16.1%), c.658_660delAAG (9.8%), c.80A > G (8.0%), and c.567dupT (6.3%). Thirty-nine patients carried the c.482G > A variant. Among 13 patients who exhibited spastic paraplegia as the main manifestation, 11 patients carried c.482G > A variants. Six patients who presented with psychotic disorders and spastic paraplegia had compound heterozygotic c.482G > A and other variants. All the patients showed improvement after metabolic treatment with cobalamin, l-carnitine, and betaine, and 30 school-aged patients returned to school. Two female patients got married and had healthy babies. Conclusions Patients with late-onset cblC deficiency present with a wide variety of neuropsychiatric symptoms and other presentations, including multiple organ damage. As a result, cb1C deficiency can easily be misdiagnosed as other conditions. Metabolic and genetic studies are important for accurate diagnosis, and metabolic treatment with cobalamin, l-carnitine, and betaine appears to be beneficial.
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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