DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for hepatic porphyria — 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 moduleHepatic porphyria 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 hepatic porphyria 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
Acute hepatic porphyria (AHP) is a group of metabolic disorders caused by altered activity of enzymes in the heme biosynthesis pathway. In AHP, the liver overproduces the porphyrin precursors delta-aminolevulinic acid and porphobilinogen, and symptoms are probably caused primarily by injury to the nervous system, though abdominal pain and nausea can occur. One case report describes metastases-like liver lesions in both porphyria cutanea tarda and AHP, noting the role of contrast-enhanced ultrasound in their evaluation.
A phase 1/2 open-label extension study (NCT02949830) followed 16 adults with acute intermittent porphyria, the most common subtype of AHP, for up to 48 months on givosiran, a subcutaneously administered RNA interference therapeutic that targets liver ALAS mRNA. The median age was 39.5 years. Common adverse events included abdominal pain, nasopharyngitis, and nausea, each occurring in 50% of patients. Injection-site erythema (38%) and injection-site pruritus (25%) were frequent treatment-related reactions. Givosiran reduced the annualised rate of porphyria attacks by 97% and annualised hemin use by 96%. From months 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. Median urinary delta-aminolevulinic acid fell by 95% and porphobilinogen by 98%. A clinically meaningful improvement in quality of life was observed on the EQ-5D-5L instrument.
The study is the longest follow-up of givosiran treatment reported to date, but it included only 16 patients and was open-label, with no control group. What remains missing is evidence from larger, randomised, controlled trials with longer follow-up, and data on whether the drug works equally well in patients with different subtypes of AHP or with varying baseline attack rates. The cost of givosiran and the need for chronic subcutaneous administration are not addressed in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Ultraschall in der Medizin - European Journal of Ultrasound · 2021 · 1 citations
Metastases-Like Liver Lesions in Two Different Types of Porphyria – Porphyria Cutanea Tarda (PCT) and Acute Hepatic Porphyria (AHP) – and the Role of CEUS
AbstractPorphyria are a group of metabolic disorders caused by altered activity of enzymes in the heme biosynthesis pathway. Acute hepatic porphyria (AHP) are due to hepatic overproduction of the porphyrin precursors, delta aminolevulinic acid, and porphobilinogen, and the symptoms are probably caused primarily by injury to the nervous system. However, abdominal pain and nausea can be observed.
Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study
AbstractAbstract Background Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18–65 years who completed part C of the Phase 1 givosiran study (NCT2452372). Methods Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. Results Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed. Conclusions In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria.
Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study
AbstractAbstract Background Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18–65 years who completed part C of the Phase 1 givosiran study (NCT2452372). Methods Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. Results Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed. Conclusions In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria.
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.
