DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for propionic acidemia — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePropionic acidemia maps to a 5-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 propionic acidemia 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
carbamoyl-phosphate synthase 1 (CPS1) — CPS1 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 4-fluorophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6UEL · 1.9 Å · ligand N~1~-[(4-fluorophenyl)methyl]-N~1~-methyl-N~4~-(4-methyl-1,3-thiazol-2-yl)piperidine-1,4-dicarboxamide (Q5A). Experimental structure, not a prediction.
What the evidence adds up to
In a retrospective review of 24 patients in Saudi Arabia, 92% had early-onset propionic acidaemia, with a mean age at diagnosis of 0.13 years. Among these patients, 75% had developmental delay, 50% had seizures, 83% were undernourished, and 75% had short stature. During metabolic crises, hyperammonaemia occurred in all 24 patients, metabolic acidosis in 83%, and hypoglycaemia in 25%. Cerebral oedema and pancytopenia each occurred in 17% of patients during crises. Two patients had intracranial haemorrhage, and one had paraplegia.
A US claims-based study of 191 patients with propionic acidaemia and 230 matched controls, with a median follow-up of 2.7 years, found that patients had more comorbidities across all age strata than controls, including neurologic and nervous system disorders, cytopenias, growth abnormalities, metabolic issues, and cardiac problems. The overall rate of metabolic decompensation events (hospitalisations with hyperammonaemia or metabolic acidosis) was 0.5 per patient-year. The highest rate was in children aged 3–6 years (1.4 per patient-year), the lowest in adolescents aged 13–17 (0.1 per patient-year), and the rate rose again in adults to 0.2 per patient-year. Only 31.4% of patients experienced any metabolic decompensation event, but those who did had a significantly higher burden of symptoms and comorbidities than those who did not.
A 2019 review describes propionic acidaemia as a rare autosomal recessive disorder caused by propionyl-CoA carboxylase deficiency, leading to multi-organ damage. The review states that most patients present in the neonatal period or early infancy, and that diagnosis relies on blood amino acids, acylcarnitines, urine organic acids, and gene testing. It lists treatment options as L-carnitine, dietary management, symptomatic intervention, and liver transplantation, and notes that without timely treatment the risk of death and disability is high.
What is still missing is prospective data on long-term outcomes beyond hospital claims, and any controlled trial evidence for the individual treatments mentioned. The US study relied on insurance claims, which may miss milder cases or events not requiring hospitalisation. No drug therapy has been shown in a randomised trial to reduce the rate of metabolic decompensation or improve developmental outcomes in propionic acidaemia.
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 Pediatric Endocrinology and Metabolism · 2013 · 16 citations
Propionic acidaemia: demographic characteristics and complicationsa
AbstractBACKGROUND: Propionic acidaemia is a global, metabolic disease, highly prevalent in Kingdom of Saudi Arabia. It may produce an array of complications which significantly deteriorate the patient's quality of life. OBJECTIVES: To find out the demographic characteristics and complications of patients with propionic acidemia. METHODS: The records of diagnosed cases of propionic acidaemia were reviewed, retrospectively. RESULTS: Of 24 patients, 16 (67%) were male. Consanguineous parents were 16 (67%). Ten (42%) patients had diseased siblings. Mean age at diagnosis was 0.13±0.27 year. Twenty-two (92%) patients had early onset and 2 (8%) had late onset disease. Eighteen (75%) patients had developmental delay, 11 (46%) had hypotonia, 3 (12%) had hypertonia, 13 (54%) had hyperreflexia and 12 (50%) had seizures. Two (8%) children each, had intracranial haemorrhage, spastic quadriplegia, hemiplegia and 1 (4%) had paraplegia. Cerebral atrophy and nasogastric/gastrotomy, tube feeding, each was found in 6 (25%) patients. Under nutrition was revealed in 20 (83%), short stature in 18 (75%), rickets in 1 (4%) and pancreatitis in 2 (8%) patients. During metabolic crisis, cerebral oedema and pancytopenia each were found in 4 (17%), hypoglycaemia in 6 (25%), hyperglycaemia in 2 (8%), hyperammonaemia in all 24 (100%) and metabolic acidosis in 20 (83%) cases. CONCLUSION: Propionic acidaemia is a rare hereditary disorder that has wide spectrum of neurological and other complications, which perhaps with early diagnosis and intervention may be preventable, more effectively.
Clinical burden of propionic acidemia in the United States: a claims-based study by age stratum
AbstractAbstract Background Patients with propionic acidemia (PA) may face recurrent metabolic decompensation events (MDEs) and multisystemic complications. This study compared characteristics and clinical outcomes of patients with PA and matched non-PA controls by age stratum. Methods Patients with PA from the US IQVIA PharMetrics Plus claims database (10/2015‒6/2022) had their follow-up time partitioned into age strata (0‒2, 3‒6, 7‒12, 13‒17, ≥ 18 years) and were matched 1:1 to randomly selected non-PA controls within each stratum. MDEs were identified as hospitalizations with claims for hyperammonemia and/or metabolic acidosis. Hospitalizations with claims for PA signs and symptoms were evaluated. Results Among 191 patients with PA and 230 matched non-PA controls (median follow-up: 2.7 years), patients with PA had more comorbidities (neurologic/nervous system, cytopenias, growth, metabolism, cardiac system; listed in order of frequency) across all age strata. The overall MDE rate for patients with PA was 0.5 per patient-year (PPY) while hospitalizations with various PA signs and symptoms ranged from 0.3 to 0.6 PPY. MDE rates were highest in those aged 3‒6 years (1.4 PPY), lowest in the 13‒17 years stratum (0.1 PPY), and rose again in adults (0.2 PPY). Patients with MDEs (31.4%) had a significantly higher burden of PA-related symptoms and comorbidities than those without; both groups showed even greater differences when compared to controls. Conclusions Patients with PA across all age strata, with and without MDEs, experience a substantial burden of disease-related comorbidities, complications, and healthcare visits compared with matched non-PA controls, which highlights the need for improved clinical outcomes in these patients.
Orphanet Journal of Rare Diseases · 2025 · 0 citations · open access
Clinical burden of propionic acidemia in the United States: a claims-based study by age stratum
AbstractBACKGROUND: Patients with propionic acidemia (PA) may face recurrent metabolic decompensation events (MDEs) and multisystemic complications. This study compared characteristics and clinical outcomes of patients with PA and matched non-PA controls by age stratum. METHODS: Patients with PA from the US IQVIA PharMetrics Plus claims database (10/2015‒6/2022) had their follow-up time partitioned into age strata (0‒2, 3‒6, 7‒12, 13‒17, ≥ 18 years) and were matched 1:1 to randomly selected non-PA controls within each stratum. MDEs were identified as hospitalizations with claims for hyperammonemia and/or metabolic acidosis. Hospitalizations with claims for PA signs and symptoms were evaluated. RESULTS: Among 191 patients with PA and 230 matched non-PA controls (median follow-up: 2.7 years), patients with PA had more comorbidities (neurologic/nervous system, cytopenias, growth, metabolism, cardiac system; listed in order of frequency) across all age strata. The overall MDE rate for patients with PA was 0.5 per patient-year (PPY) while hospitalizations with various PA signs and symptoms ranged from 0.3 to 0.6 PPY. MDE rates were highest in those aged 3‒6 years (1.4 PPY), lowest in the 13‒17 years stratum (0.1 PPY), and rose again in adults (0.2 PPY). Patients with MDEs (31.4%) had a significantly higher burden of PA-related symptoms and comorbidities than those without; both groups showed even greater differences when compared to controls. CONCLUSIONS: Patients with PA across all age strata, with and without MDEs, experience a substantial burden of disease-related comorbidities, complications, and healthcare visits compared with matched non-PA controls, which highlights the need for improved clinical outcomes in these patients.
Screening, diagnosis and treatment of propionic academia
AbstractPropionic acidemia or propionic aciduria, is a rare autosomal recessive inherited metabolic disease.It is a metabolic disorder of branched amino acids and odd-chain fatty acids caused by propionyl-CoA carboxylase deficiency, resulting in brain, heart, liver, bone marrow or multi-organ damages leading to disabilities even death.Patients with propionic acidemia have various clinical manifestations.Most patients presented in the neonatal period or early infancy.Nonspecific clinical presentations of the patients make the clinical diagnosis difficult, a definite diagnosis relies on the blood amino acids and acylcarnitines determination, urine organic acids analysis, and gene testing.The treatment for the patients in acute and stable phase should be individualized, including L-carnitine, dietary management, symptomatic intervention and liver transplantation.If not treated timely, patients have a high risk of death and disability.Early screening, diagnosis and treatment can greatly improve the patients′ clinical outcomes.
Key words:
Propionic acidemia; Inherited metabolic disease; Diagnosis; Treatment
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.
