DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for acute intermittent porphyria — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAcute intermittent porphyria maps to a 3-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 acute intermittent 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.
Molecular view
hydroxymethylbilane synthase (HMBS) — HMBS 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 2-hydroxy-2-oxoethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7AAK · 1.7 Å · ligand 3-[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-5-[[4-(2-hydroxy-2-oxoethyl)-3-(3-hydroxy-3-oxopropyl)-5-methyl-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-3-(3-hydroxy-3-oxopropyl)-1~{H}-pyrrol-2-yl]methyl]-1~{H}-pyrrol-3-yl]propanoic acid (7J8). Experimental structure, not a prediction.
What the evidence adds up to
Acute intermittent porphyria is frequently missed or diagnosed late. Several case reports describe patients with clear neurological, gastrointestinal, and respiratory symptoms whose diagnosis was delayed for considerable periods, sometimes until respiratory failure had set in. One 2015 paper notes that delaying diagnosis and treatment can be fatal or cause permanent neurological damage. A 2006 study of five unrelated patients found that biochemical and molecular diagnostic methods corresponded well, and that asymptomatic gene carriers could be identified within families — in one family, the patient's son was a carrier but the daughter was not.
A 2023 retrospective study of 29 patients with acute intermittent porphyria examined long-term management. Patients were grouped by attack frequency in the first two years after diagnosis: 19 had fewer than four attacks per year, and 10 had four or more per year. All patients experienced fewer attacks over the treatment course, and 23 of 29 (79.3%) were attack-free in the most recent two-year period. Among the nine patients who received pharmacological prophylaxis (seven with weekly heme arginate, one with givosiran, one with heme arginate followed by givosiran), five (55.6%) were attack-free in the most recent two years, and prophylaxis was stopped in some because no attacks had occurred for over a year. Among the 20 patients who did not receive prophylaxis, 18 (90.0%) were attack-free in the most recent two years, and 15 (75.0%) had attacks only in the first two years after diagnosis. The authors concluded that prophylaxis could be considered for patients with four or more biochemically confirmed attacks per year after one to two years of routine treatment, but that more studies are needed to reach a consensus.
The evidence for pharmacological prophylaxis in acute intermittent porphyria comes from a single small retrospective study with no randomised control group. The study itself calls for more research to establish consensus. What is still missing are prospective trials large enough to stratify patients by attack frequency and biochemical profile, and to determine whether the apparent benefit of prophylaxis over time is due to the drugs, to the natural history of the disease, or to other aspects of management. Funding for such trials, and for standardised diagnostic pathways to reduce the persistent delays in recognition, remains inadequate.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Practical Neurology · 2018 · 59 citations
Porphyria: often discussed but too often missed
AbstractThe diagnosis of acute intermittent porphyria (AIP) is often overlooked. We describe a patient with this condition who had all the 'bells and whistles', in whom the diagnosis was only made after considerable delay. Far from an esoteric condition haunting examination candidates, AIP is an important cause of a broad spectrum of neurological symptoms. Its early recognition allows the astute clinician to prevent potentially devastating sequelae. We provide practical guidance on the investigation and management of this complex disorder. With a 'back to basics' approach to the underlying genetics and biochemistry, we hope to dispel some of the confusion that may obstruct a timely diagnosis.
Hepatology Communications · 2023 · 6 citations · open access
Long-term management and treatment of acute intermittent porphyria with recurring attacks using pharmacological prophylaxis
AbstractBACKGROUND: There is no definitive guidance on whether patients with acute intermittent porphyria (AIP) with recurrent attacks need pharmacological prophylactic treatment. METHODS: The management strategies for patients with frequent (defined as ≥4 annualized attack rate (AAR) and less frequent attacks (<4 AAR), including treatment for acute attacks and duration of prophylaxis (weekly heme arginate 3 mg/kg body weight and/or investigational drug, givosiran), were summarized. The AAR for the following periods were presented: the first 2 years after diagnosis, before/after prophylaxis, and the most recent 2 years. RESULTS: A total of 29 patients with AIP were included, 19 (34.5%) had <4 AAR and 10 (65.6%) had ≥4 AAR in the first 2 years after diagnosis. All patients experienced reduced attacks during the treatment course, 23 (79.3%) were attack-free during the most recent 2 years. Among the 9 patients who received prophylaxis (7 heme arginate; 1 givosiran, 1 heme arginate followed by givosiran), 5 (55.6%) were attack-free in the most recent 2-year period and prophylaxis was discontinued because there had been no attacks for >1 year. For patients without prophylaxis (n = 20), 18 (90.0%) were attack-free in the most recent 2-year period and 15 (75.0%) experienced attacks only in the first 2 years after diagnosis. CONCLUSIONS: Prophylaxis could be considered for patients with AIP with ≥4 biochemically confirmed attacks/year after routine treatment of 1-2 years, during which the severity and frequency of attacks should be closely monitored to determine the necessity of pharmacologic prophylaxis. More studies are needed to reach a consensus on the use of pharmacological prophylaxis and treatment of AIP.
Acute Intermittent Porphyria in a Child with a Note on the Glycine Loading Test
AbstractA case of acute intermittent porphyria in a 6-year-old boy is described. Screening of urine specimens from his family showed elevated ALA and PBG levels in a 12-year-old brother. Administration of glycine (0.4 gm/kg) to the patient resulted in increased urinary output of ALA and PBG. Coproporphyrin appeared in the urine of the patient and one brother after glycine. Normal results were obtained in another brother and two control children.
Journal of Inherited Metabolic Disease · 2006 · 4 citations
Biochemical compared to molecular diagnosis in acute intermittent porphyria
AbstractThe biochemical and the molecular diagnoses of an inherited porphyria require experience. False positive or negative screening tests and the low penetrance of the disease make a correct diagnosis difficult.The biochemical and the molecular procedures for the diagnosis of acute intermittent porphyria were applied to five unrelated patients suffering from acute intermittent porphyria. All patients were shown to be gene carriers of acute intermittent porphyria by both methods. The two different possibilities of the diagnosis corresponded well. In a family definitively identified by molecular diagnosis of one of the patients and his relatives, the patient's two children were asymptomatic. His son was shown to be a gene carrier of the father's deficiency by biochemical as well as molecular analysis, whereas his daughter was not affected by acute intermittent porphyria.
Respiratory Insufficiency Associated With Acute Intermittent Porphyria
AbstractAcute intermittent porphyria (AIP) is a disease that may present with gastrointestinal, psychiatric, or neurologic symptoms. We describe two patients in whom AIP was first diagnosed during episodes of acute respiratory insufficiency. The biochemical defects, clinical presentations, pathophysiology, diagnostic criteria, and treatment of AIP are reviewed. We emphasize that AIP should be considered in the differential diagnosis of every patient with unexplained respiratory failure. Once considered, AIP is relatively simple to diagnose and specific therapeutic measures can be instituted.
Journal of Anaesthesiology Clinical Pharmacology · 2015 · 2 citations · open access
Acute intermittent porphyria: Diagnostic dilemma and treatment options
AbstractAcute intermittent porphyria (AIP) presents with diverse group of symptoms making its early diagnosis difficult. Delaying diagnosis and treatment of AIP can be fatal or can cause long term or permanent neurological damage. We present here a case report of AIP where the diagnosis was missed. The diversity of symptoms and details concerning the treatment options for AIP are discussed.
AACN Clinical Issues Advanced Practice in Acute & Critical Care · 1994 · 0 citations
Caring for Patients With Acute Intermittent Porphyria
AbstractThe porphyrias are a group of metabolic disorders of heme biosynthesis genetically determined defects. Acute intermittent porphyria is the most common form of porphyria found in the United States. It is caused by a genetic defect in chromosome 11, where one of two genes for porphobilinogen deaminase is defective. Acute intermittent porphyria is characterized by intermittent, acute, occasionally fatal attacks of abdominal, neurologic, psychiatric, and renal symptoms. Attacks are often confused with acute abdomen or bowel obstruction. A variety of drug, hormonal, nutritional, and infectious factors can precipitate clinical symptoms. Managing patients with acute intermittent porphyria involves removing the precipitating factors, increasing carbohydrate intake, controlling pain, and administering medications. A case study is provided.
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.
