DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for triple-A syndrome — 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 moduleTriple-A syndrome 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 triple-a syndrome 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
GDP-mannose pyrophosphorylase A (GMPPA) — GMPPA 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 gdddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7D73 · 3.0 Å · ligand GUANOSINE-5'-DIPHOSPHATE-ALPHA-D-MANNOSE (GDD). Experimental structure, not a prediction.
What the evidence adds up to
No drug treatment for triple-A syndrome itself is described in these abstracts. Two case reports and one case series detail the clinical presentation and management of symptoms. In one 2017 report, two sisters with confirmed Allgrove syndrome received pneumatic balloon dilatation for achalasia and cortisone therapy for adrenal insufficiency, which resolved dysphagia and other symptoms. A 2018 report describes two unrelated patients: a 3.5-year-old girl with adrenal insufficiency and alacrima, and an 8-month-old boy with achalasia, alacrima, and neurological abnormalities. Both were diagnosed clinically; the girl had a confirmed AAAS gene mutation, the boy did not. No drug was given to either patient in that report.
The remaining three abstracts are irrelevant to triple-A syndrome. One reviews investigational drugs for hepatitis C, one compares triple versus quadruple therapy for Helicobacter pylori eradication, and one reports a case of oesophageal small cell carcinoma treated with chemotherapy, radiation, and surgery. None of these papers test a drug for triple-A syndrome, and no drug from them is proposed for repurposing in that disease.
What is missing is any clinical trial of a drug intended to modify the course of triple-A syndrome. The literature provides only symptomatic management—corticosteroids for adrenal failure and mechanical dilatation for achalasia. No molecular target has been tested in patients, no repurposing screen has been published, and no funding for such a trial is described. Patient stratification by AAAS mutation type and neurological phenotype would be needed before any experimental therapy could be evaluated.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Expert Opinion on Investigational Drugs · 2009 · 42 citations
Investigational drugs for hepatitis C
AbstractIMPORTANCE OF THE FIELD: Hepatitis C virus (HCV) infection affects 180 million people worldwide. Standard anti-HCV therapy combines effect of pegylated IFN-alpha on immune response and antiviral activity of ribavirin. Sustained virological response rate achieved with this standard of care medication is around 50% for HCV genotype 1, the most prevalent worldwide genotype. So there is an obvious need to enhance efficacy of treatment. AREAS COVERED IN THIS REVIEW: We describe novel treatment options studied within the recent few years, which are focused on inhibitors of HCV-specific enzymes such as NS3/4 protease and NS5B polymerase or influence host-virus interactions. WHAT THE READER WILL GAIN: According to the most recent data, triple therapies consisted of pegylated interferons, ribavirin and protease inhibitors demonstrate significant improvement of treatment efficacy in comparison to current standard of care medication. Moreover, new forms of interferons and ribavirin, more effective, less toxic, and more convenient, become probably a fundamental component of anti-HCV therapy in the near future. TAKE HOME MESSAGE: In coming years, we can expect that triple therapy becomes a standard medication, and treatment without interferon and/or ribavirin becomes a new studied therapeutic scenario.
BMC Pediatrics · 2018 · 23 citations · open access
“Crying without tears” as an early diagnostic sign-post of triple A (Allgrove) syndrome: two case reports
AbstractBACKGROUND: Triple A syndrome (or Allgrove syndrome) is a rare autosomal recessive disorder characterized by alacrima, achalasia, adrenal insufficiency and autonomic/neurological abnormalities. The majority of cases are caused by mutations in the AAAS gene located on chromosome 12q13. However, the clinical picture as well as genetic testing may be complex since symptomatology is variable and mutations cannot be identified in all clinically diagnosed patients. We present two unrelated patients with triple-A syndrome illustrating the importance of alacrima as an early clinical sign. CASE PRESENTATION: A 3.5 year old girl presented with repeated hypoglycaemic myoclonic events. Adrenal insufficiency was diagnosed. In addition, alacrima, obvious since early infancy, was incidentally reported by the mother and finally lead to the clinical diagnosis of triple A syndrome. This was confirmed by positive mutation analysis of the AAAS gene. The second patient, an 8 months old boy was presented because of anisocoria and unilateral optic atrophy. MRI revealed cerebellar vermis hypotrophy. Psychomotor retardation, failure to thrive, and frequent vomiting lead to further diagnostic work-up. Achalasia was diagnosed radiologically. In addition, the mother mentioned absence of tears since birth leading to the clinical diagnosis of triple A syndrome. In contrast to the first cases genetic testing was negative. CONCLUSION: These two patients illustrate the heterogeneity of triple A syndrome in both terms, clinical expression and genetic testing. We particularly aim to stress the importance of alacrima, which should be considered as a red flag symptom. Further differential diagnosis is required in every child affected by alacrima.
World Journal of Gastroenterology · 2008 · 21 citations · open access
Treatment of Helicobacter pylori in surgical practice: A randomised trial of triple versus quadruple therapy in a rural district general hospital
AbstractAIM: To compare a lansoprazole-based triple versus quadruple therapy for Helicobacter pylori (H pylori) eradication with emphasis on side effect profile, patient compliance and eradication rate at a rural district general hospital in Wales, United Kingdom. METHODS: One hundred one patients with H pylori infection were included in the study. Patients were randomised to receive triple therapy comprising of lansoprazole 30 mg, amoxycillin 1 g, clarithromycin 500 mg, all b.d. (LAC), or quadruple therapy comprising of lansoprazole 30 mg b.d., metronidazole 500 mg t.d.s., bismuth subcitrate 240 mg b.d., and tetracycline chloride 500 mg q.d.s. (LMBT). Cure was defined as a negative (13)C urea breath test 2 mo after treatment. RESULTS: Seven patients were withdrawn after randomisation. Fifty patients were assigned to LAC group and 44 to LMBT group. The intention-to-treat cure rates were 92% and 91%, whereas the per-protocol cure rates were 92% and 97%, respectively. Side effects were common, with 56% experiencing moderate to severe symptoms in the LAC group and 59% in the LMBT group. Symptoms of vomiting, diarrhoea and black stools were significantly more common in the LMBT group. Patient compliance was 100% for triple therapy and 86% for quadruple therapy (P < 0.01). One-third of patients in both groups were still taking acid-reducing medications at six-month follow-up. CONCLUSION: One-week triple and quadruple therapies have similar intention-to-treat eradication rates. Certain side effects are more common with quadruple therapy, which can compromise patient compliance. Patient education or modifications to the regimen are alternative options to improve compliance of the quadruple regimen.
Pakistan Journal of Medical Sciences · 2017 · 10 citations · open access
AAA Syndrome, Case Report of a Rare Disease
AbstractTriple A (Allgrove) syndrome, an autosomal recessive disease is characterized by achalasia, alacrimia and ACTH-resistant adrenal failure with progressive neurological syndrome including central, peripheral and autonomic nervous system impairment, and mild mental retardation. The triple A syndrome gene, designated AAAS, localized on chromosome 12q 13 encodes for a 546 amino acid protein called ALADIN (Alacrimia-Achlasia-Adrenal Insufficiency and Neurologic disorder). This report relates to two sisters, aged 8 and 12 years, who had vomiting, muscle weakness, alacrimia, excessive fatigue and dysphagia. Abdominal sonography, esophago-gastroduodenoscopy, barium swallow, esophageal manometry, CT scan abdomen and brain, biochemical profiles, as well as neurologic and ophthalmic evaluations were consistent with Allgrove's syndrome. Management consisted of pneumatic balloon dilatation for achalasia and initiation of cortisone therapy with successful resolution of dysphagia and other symptoms.
Anticancer Research · 2020 · 2 citations · open access
First Reported Case of Localized Extra-pulmonary Small Cell Carcinoma (EPSC) of the Esophagus Treated With Triple Therapy
AbstractBACKGROUND/AIM: Early stage extra-pulmonary small cell carcinoma (EPSC) of the esophagus is very rare and is usually treated with chemo-radiation or surgical resection. CASE REPORT: A case of early stage small cell carcinoma of the esophagus that was treated with all three current modalities of chemotherapy, radiation, and surgery. To our best knowledge this is the first case treated with triple therapy. The patient is a 64-year-old male with increasing gastroesophageal reflux disease (GERD) symptoms. EGD biopsy of the mass showed small cell carcinoma. Metastatic work up was negative. Patient was treated with 6 cycles of a platinum-based agents and Etoposide along with radiation. Patient underwent distal esophagectomy. Patient is alive without evidence of recurrent disease at 20 months follow up. CONCLUSION: Currently there are no definite treatment recommendations, but we present a possible future option with good outcomes in patients who can tolerate triple therapy.
Indian Journal of Genetics and Molecular Research · 2020 · 0 citations · open access
Triple X Syndrome: An Appraisal Under Review Study
AbstractThe Triple X syndrome is an anomalous genetic condition distinguished by an extra X chromosome in each cell of the female body. This manuscript is prepared with the objectives of giving a better understanding and summarizing the current status of the Triple X syndrome cases and to be used by individuals to understand best about this abnormality. This syndrome was first identified in 1959. The Triple X females are usually with normal fertility and sexual development, so able to conceive children and lead productive lives. Mostly there are no any obvious physical differences other than often taller stature than average in these cases. In some cases the symptoms may be more apparent including developmental, psychological and behavioral problems and may lead to a number of other ill health including work, school, social and relationship problems like learning difficulties and delayed development of speech and language skills; decreased muscle tone / weakness / hypotonia and delayed development of motor skills such as sitting and walking; behavioral and emotional difficulties; seizures and kidney problems. For these problems they need additional support and assistance. The cause of this syndrome is an accidental event during cell division and resulted either during the division of the mother's reproductive cells or during the division of cells at the beginning of development of zygote. The Triple X syndrome is not typically inherited or run from one generation to the next. A form where only a percentage of the body cells contain XXX can also occur. Diagnosis is by the karyotyping or chromosomal analysis. The treatment may include the speech and physical therapy and the counseling. The prevalence rate of the Triple X syndrome is around 1 in 1,000 girls. It is estimated that 90% of those affected are not diagnosed as they either have no or only few symptoms. The parents should talk with a doctor about disquiets with the development of their daughters which will help girls receive an early diagnosis and interventions. The researches have shown that early treatments at younger age are more effective towards normalcy of life in the Triple X cases. Adolescents and adult women presenting with late menarche, menstrual irregularities, or fertility problems should be evaluated first for the premature ovarian failure and Triple X syndrome.
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.
