DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for hereditary coproporphyria — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary coproporphyria maps to a 4-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 hereditary coproporphyria 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
galactosidase alpha (GLA) — GLA 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 2pedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3HG3 · 1.9 Å · ligand NONAETHYLENE GLYCOL (2PE). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary coproporphyria (HCP) is the rarest of the autosomal dominant acute porphyrias, with an estimated incidence of 0.02 per 10 million per year. It is often misdiagnosed, most commonly presenting as atypical neuropsychiatric symptoms or acute abdominal pain. One case report describes a 22-year-old male with a history of six recurrent intestinal obstructions who presented with reduced upper limb strength, photosensitive rash, and abdominal pain. Laboratory tests showed increased levels of coproporphyrin, uroporphyrinogen, and porphyrin in stool, with porphobilinogen deaminase activity within the normal range, leading to the diagnosis. Single intravenous glucose therapy improved his condition, and no relapse was observed during a 3-month follow-up.
A family series of seven members with a novel mutation reports penetrance confirmed at 57% and suspected to be 71%, which is high compared to the general estimate that 90% of patients with a mutation never exhibit symptoms. Four of the seven had recurrent attacks, and the first patient experienced life-threatening complications. The development of opioid dependence complicated management. The series also documents a high rate of veno-thromboembolism. The use of the mRNA interference molecule givosiran is noted in this family, as is the use of ketamine for acute attacks, reported for the first time in the porphyria literature. A plan for embryo selection was also used, which is not common in porphyria.
A case report from 2011 illustrates the broad manifestations, unsuspected diagnosis, and difficulties in management of HCP, emphasising that proper identification can lead to less iatrogenicity from porphyrinogenic agents. The authors note that clinicians should suspect acute porphyrias in patients with variable neuropsychiatric symptoms and unexplained pain.
What is still missing are large, systematic data. The disease is so rare that characterisation and management depend on international registries, which are not yet established. No controlled trial data exist for any intervention in HCP specifically. The evidence for glucose therapy, givosiran, or ketamine comes from single cases or one family series, with no randomised comparisons. Patient stratification by mutation type, attack severity, or thrombotic risk remains unstudied. Funding for a registry or a dedicated trial in this ultra-rare condition has not been secured.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
QJM · 1977 · 84 citations
Hereditary Coproporphyria
AbstractHereditary coproporphyria is biochemically distinct from the other porphyrias and is characterized by excessive excretion of coproporphyrin in faeces and usually in urine. The laboratory findings in 28 patients with this disease are presented and the clinical details of eight patients who have been in attack summarised. The remaining 20 patients were latent for the disease. In all patients studied the activity of delta-aminolaevulinic acid synthase was raised and coproporphyrinogen oxidase depressed in the leucocyte. This indicates the partial enzyme block in the haem biosynthetic pathway in this disease. The activities of the other enzymes in the pathway, leucocyte ferrochelatase and erythrocyte delta-aminolaevulinic acid dehydratase, porphobilinogen deaminase and uroporphyrinogen decarboxylase showed no consistent change. On review of 111 cases, 35 per cent presented in acute attack: 80 per cent had abdominal pain, 34 per cent vomiting, 29 per cent solar sensitivity, 23 per cent neurological involvement, 23 per cent psychiatric symptoms and 20 per cent severe constipation. Only two fatalities have been published, both from respiratory failure. There was a female preponderance of cases in attack of 2-5:1 and in the latent cases of 1-5:1 suggesting hormonal provocation in the uncovering of the disease. Drugs were implicated as precipitating 54 per cent of acute attacks and in 34 per cent of cases, these were barbiturates. This study demonstrates the reduction in activity of coproporphyrinogen oxidase in the haem biosynthetic pathway and the elevation of delta-aminolaevulinic acid synthase in the peripheral blood. These features, together with the typical abnormal porphyrin excretion pattern, appear to be diagnostic of hereditary coproporphyria whether in attack, remission, or in the latent form.
The Primary Care Companion For CNS Disorders · 2011 · 10 citations
Schizoaffective Disorder With Missed Diagnosis of Acute Porphyria: A Case Report and Overview
AbstractAcute porphyrias are often misdiagnosed and most commonly present as atypical neuropsychiatric symptoms or acute abdominal pain. Clinicians should suspect acute porphyrias in patients presenting with variable neuropsychiatric symptoms and unexplained pain. Proper identification can lead to less iatrogenicity associated with porphyrinogenic agents, appropriate management, and a better patient outcome. The case of a patient with hereditary coproporphyria, one of the acute porphyrias, is presented to illustrate the broad manifestations, unsuspected diagnosis, and difficulties in management.
High penetrance, recurrent attacks and thrombus formation in a family with hereditary coproporphyria
AbstractHereditary coproporphyria (HCP) is the rarest of the autosomal dominant acute porphyrias with an estimated incidence of 0.02 per 10 million per year. HCP has been considered to be mild in presentation compared with the more common acute intermittent porphyria although there is limited information comparing the subtypes. Penetrance in the acute porphyrias is low with 90% of patients with a mutation never exhibiting symptoms. We present seven members from a family with HCP with a novel mutation in whom penetrance and severity are high. In addition, they appear to have a high rate of veno-thromboembolism. Penetrance is confirmed at 57% but is suspected to be 71%. The first patient experienced life-threatening complications, four of the seven have had recurrent attacks and the development of opioid dependence has complicated management. The case series documents the impact of a new mRNA interference molecule givosiran as well as a plan for embryo selection which is not commonly used in porphyria. The use of ketamine for the treatment of acute attacks is also documented for the first time in the porphyria literature. The use of international registries would aid the characterisation and management of this very rare disease.
Hereditary Coproporphyria Presenting with Weakness and Photosensitive Rash: A case Report and Literature Review
AbstractHereditary coproporphyria (HCP) is a form of porphyria arising from a deficiency of the enzyme, coproporphyrinogen oxidase, which results in the accumulation of coproporphyrin in the heme biosynthetic pathway. In the current study, we report a case of a 22-year-old male with a history of six recurrent intestinal obstructions, mainly presenting with reduced upper limb strength, photosensitive rash, and abdominal pain this admission. The laboratory tests revealed increased levels of coproporphyrin, uroporphyrinogen and porphyrin in stool sample and porphobilinogen deaminase activity was within the normal range. All these led to the diagnosis for HCP. Single intravenous glucose therapy improved the patient’s condition and no relapse was observed during the 3-month follow-up period. Since then, no other pathological or genomic manifestations were observed.
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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