DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for histidinemia — 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 moduleHistidinemia 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 histidinemia 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.
What the evidence adds up to
Histidinemia is a disorder of histidine metabolism characterised by elevated plasma histidine and absent or decreased skin histidase activity. In one family, nine new cases were found across four sibships and two successive generations, with a normal father and no consanguinity; the inheritance pattern was described as autosomal dominant, and the affected individuals were considered an intermediate genotype between typical histidinemics and normal subjects because they excreted decreased amounts of N-formiminoglutamic acid after histidine loading (1970). In another report, two brothers aged 6 and 13 both had histidinemia, but the younger was judged to have the classical type while the older had an atypical form with partial skin histidase impairment and a moderately prolonged half-life of blood histidine; the mother was a heterozygous carrier, the father and sister normal (1975).
The relationship between the biochemical defect and clinical findings remains unclear. In two families studied over five years, one 13-year-old girl had only slight mental retardation but a severe emotional problem, with a fasting blood histidine of 10.4 mg/100 ml; her younger sister had near normal intelligence, repeated kindergarten, and a marked speech defect (1967). The authors noted that the mental retardation observed in some children might be familial rather than caused by the histidinemia itself (1967). Speech defects were found in most cases, but no consistent pattern of intellectual impairment emerged from these small samples.
Histamine metabolism is elevated in histidinemic patients. Urinary excretions of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugates were higher than in controls, and these levels correlated with plasma histidine concentration (2005). Patients with eczema-like dermatitis had urinary histamine levels twice those without dermatitis, and urinary 3-methylhistidine excretion correlated closely with urinary histidine excretion (2005). These findings suggest a link between histidine load and histamine production, but the clinical significance for speech or cognition is not established.
What is missing is any large, systematic study that separates the biochemical effects of histidinemia from familial intellectual disability, and no controlled trial of any dietary or pharmacological intervention has been reported. The natural history of the condition across a broad, unselected population remains unknown, and no validated biomarker predicts which individuals will develop speech defects or dermatitis. Patient stratification by genotype, residual enzyme activity, and histamine metabolite profile has not been attempted in a prospective cohort.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Pediatrics and Adolescent Medicine · 1970 · 28 citations
Histidinemia in Two Successive Generations
AbstractNine new cases of histidinemia have been found in four different sibships and in two successive generations in the same family. No history of consanguinity is present. The father of the propositus is normal. The pattern of inheritance appears to be autosomal dominant. Since these patients have absent or decreased skin histidase activity and they excrete decreased amounts of N-formiminoglutamic acid following histidine loading, they probably represent an intermediate genotype between the typical histidinemics and individuals with normal skin histidase.
Archives of Pediatrics and Adolescent Medicine · 1967 · 16 citations
Variations in Clinical and Laboratory Findings in Histidinemia
AbstractIT HAS BEEN more than five years since Ghadimi first described histidinemia; while the disease is apparently caused by an enzymatic defect, absence of histidase, there is no ready explanation of the relationship between the increased level of this plasma amino acid and the speech defects found in most cases. What has not been appreciated, perhaps, is the fact that the mental retardation observed in some of these children may be familial rather than due to the histidinemia. Two families which have come to our attention within the past five years varied considerably in both the biochemical characteristics and clinical findings. In the first family, a girl 13 years of age, is only slightly mentally retarded, but has a severe emotional problem. Her fasting blood histidine level was 10.4 mg/100 ml. Her younger sister has near normal intelligence, repeated kindergarten, has a marked speech defect, but has a fasting histidine
American journal of diseases of children · 1975 · 7 citations
Histidinemia
AbstractTwo brothers, 6 and 13 years old, had histidinemia. On the basis of clinical and biochemical observations, the younger boy was considered to have a classical type of the disease, while the older boy had an atypical form characterized by partial impairment of the skin histidase activity and a moderately prolonged half-life of blood histidine. The mother is a heterozygous carrier, while the father and sister seem to be normal.
AbstractHistamine metabolism in histidinemic patients was studied by measuring the urinary levels of histamine and its metabolites. The urinary excretions of histamine, N tau-methylhistamine, imidazole acetic acid, and its conjugate(s) were higher in patients with histidinemia than in controls, and these levels of excretion were correlated with the plasma histidine level. The urinary histamine levels of patients with eczema-like dermatitis were twice that of those without dermatitis. The urinary excretion of 3-methylhistidine showed a close correlation with the urinary histidine excretion. Thus, it was concluded that histamine metabolism is higher in histidinemic patients than in normal controls.
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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