DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Zellweger spectrum disorders — screening already-approved drugs against its 14-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleZellweger spectrum disorders maps to a 14-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 zellweger spectrum disorders 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
peroxisomal biogenesis factor 5 (PEX5) — PEX5 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-ethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4KYO · 2.2 Å · ligand 2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL (BTB). Experimental structure, not a prediction.
What the evidence adds up to
A 2022 meta-analysis of 107 studies covering 307 patients, combined with chart review of 136 individuals from a natural history study, found that common clinical findings in Zellweger spectrum disorder differ significantly across severity categories. These include seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and shortened lifespan. Additional significant differences were found for failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. A model using the number of clinical findings among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, together with plasma C26:0 fatty acid levels, could differentiate severity categories. This is the largest characterisation of clinical findings in relation to overall disease severity in ZSD.
A 2020 exome sequencing report identified PEX6 mutations in three patients from two unrelated families who were initially diagnosed with retinitis pigmentosa and hearing impairment. Beyond deaf-blindness, both families had enamel alteration and abnormal peroxisomes. One sibling had mild neurodevelopmental delay and nephrolithiasis; the other had intellectual disability, enamel alteration, and dysmorphism. The authors conclude that these cases represent milder forms of Zellweger spectrum disorder, expanding the phenotypic spectrum of peroxisomal biogenesis disorders.
A 2021 study of an Iranian family with Zellweger syndrome identified a point mutation in the PEX1 gene. The condition is described as a severe autosomal recessive disorder with hypotonia, intellectual disability, and hepatic enlargement. A 2024 Spanish-language case report describes a three-month-old female infant with typical facial dysmorphism who died at 14 months after repeated bronchopneumonias and no psychomotor progress.
What is still missing are validated, severity-stratified outcome measures for clinical trials, prospective natural history data from larger and more diverse cohorts, and any published interventional trial testing a drug in Zellweger spectrum disorder. The 2022 meta-analysis notes that its findings are intended to help determine appropriate outcomes for specific subjects in future trials, but no such trial results are yet available.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cells · 2022 · 37 citations · open access
Characterization of Severity in Zellweger Spectrum Disorder by Clinical Findings: A Scoping Review, Meta-Analysis and Medical Chart Review
AbstractZellweger spectrum disorder (ZSD) is a rare, debilitating genetic disorder of peroxisome biogenesis that affects multiple organ systems and presents with broad clinical heterogeneity. Although severe, intermediate, and mild forms of ZSD have been described, these designations are often arbitrary, presenting difficulty in understanding individual prognosis and treatment effectiveness. The purpose of this study is to conduct a scoping review and meta-analysis of existing literature and a medical chart review to determine if characterization of clinical findings can predict severity in ZSD. Our PubMed search for articles describing severity, clinical findings, and survival in ZSD resulted in 107 studies (representing 307 patients) that were included in the review and meta-analysis. We also collected and analyzed these same parameters from medical records of 136 ZSD individuals from our natural history study. Common clinical findings that were significantly different across severity categories included seizures, hypotonia, reduced mobility, feeding difficulties, renal cysts, adrenal insufficiency, hearing and vision loss, and a shortened lifespan. Our primary data analysis also revealed significant differences across severity categories in failure to thrive, gastroesophageal reflux, bone fractures, global developmental delay, verbal communication difficulties, and cardiac abnormalities. Univariable multinomial logistic modeling analysis of clinical findings and very long chain fatty acid (VLCFA) hexacosanoic acid (C26:0) levels showed that the number of clinical findings present among seizures, abnormal EEG, renal cysts, and cardiac abnormalities, as well as plasma C26:0 fatty acid levels could differentiate severity categories. We report the largest characterization of clinical findings in relation to overall disease severity in ZSD. This information will be useful in determining appropriate outcomes for specific subjects in clinical trials for ZSD.
Journal of Medical Case Reports · 2017 · 15 citations · open access
Identification of a novel mutation in PEX10 in a patient with attenuated Zellweger spectrum disorder: a case report
AbstractBACKGROUND: The peroxisome biogenesis disorders, which are caused by mutations in any of 13 different PEX genes, include the Zellweger spectrum disorders. Severe defects in one of these PEX genes result in the absence of functional peroxisomes which is seen in classical Zellweger syndrome. These patients present with hypotonia and seizures shortly after birth. Other typical symptoms are dysmorphic features, liver disease, retinal degeneration, sensorineural deafness, polycystic kidneys, and the patient does not reach any developmental milestones. CASE PRESENTATION: We report a case of a patient with Zellweger spectrum disorder due to a novel mutation in the PEX10 gene, presenting with a mild late-onset neurological phenotype. The patient, an Assyrian girl originating from Iraq, presented with sensorineural hearing impairment at the age of 5 followed by sensorimotor polyneuropathy, cognitive delay, impaired gross and fine motor skills, and tremor and muscle weakness in her teens. Analyses of biochemical markers for peroxisomal disease suggested a mild peroxisomal defect and functional studies in fibroblasts confirmed the existence of a peroxisome biogenesis disorder. Diagnosis was confirmed by next generation sequencing analysis, which showed a novel homozygous mutation (c.530 T > G (p.Leu177Arg) (NM_153818.1)) in the PEX10 gene predicted to be pathogenic. CONCLUSIONS: This case highlights the importance of performing biochemical, functional, and genetic peroxisomal screening in patients with clinical presentations milder than those usually observed in Zellweger spectrum disorders.
Exome sequencing identifies <i>PEX6</i> mutations in three cases diagnosed with Retinitis Pigmentosa and hearing impairment.
AbstractPurpose: The aim of the present work is the molecular diagnosis of three patients with deafness and retinal degeneration. Methods: Three patients from two unrelated families were initially analyzed with custom gene panels for Usher genes, non-syndromic hearing loss, or inherited syndromic retinopathies and further investigated by means of clinical or whole exome sequencing. Results: , a gene typically involved in peroxisomal biogenesis disorders (PBDs). Beside deaf-blindness, both families showed additional features: Siblings from Family 1 showed enamel alteration and abnormal peroxisome. In addition, the brother had mild neurodevelopmental delay and nephrolithiasis. The case II:1 from Family 2 showed intellectual disability, enamel alteration, and dysmorphism. Conclusions: presenting with milder forms of the Zellweger spectrum disorders (ZSD). The three cases showed distinct clinical features. Thus, expanding the phenotypic spectrum of PBDs and ascertaining exome sequencing is an effective strategy for an accurate diagnosis of clinically overlapping and genetically heterogeneous disorders such as deafness-blindness association.
Journal of Advances in Medical and Biomedical Research · 2021 · 2 citations · open access
Identification of the Peroxisomal Biogenesis Factor 1 Gene Point Mutation in an Iranian Family with Zellweger Syndrome (ZS)
AbstractBackground & Objective: Peroxisome biogenesis disorders (PBDs) are a group of diseases with peroxisomal dysfunction. Wide range of symptoms are associated with the disease which are due to mutations in the PEX genes. The PEX1 mutation occurs in Zellweger syndrome (ZS), a severe autosomal recessive condition with hypotonia, intellectual disability, and hepatic enlargement. The present study determined the molecular aspects of ZS in a family in South Khorasan Province, Iran.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
síndrome de zellweger pdf
Abstractsíndrome de zellweger pdf Rating: 4.6 / 5 (1534 votes) Downloads: 5375 = = = = = CLICK HERE TO DOWNLOAD = = = = = A prototypic case of Zellweger's syndrome in a suckling baby from the female sex and being three-month old is presented, with typical facial dimorphism, The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. These infants experience weak muscle tone Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal Description. The Zellweger spectrum is a clinical and biochemical continuum which can roughly be divided into three clinical phenotypes. A rare peroxisome biogenesis disorder (the most severe variant of Peroxisome biogenesis disorder spectrum) characterized by neuronal migration defects in the brain, dysmorphic craniofacial features, profound hypotonia, neonatal seizures, and liver dysfunction. Todo el contenido de esta revista, Introducción El síndrome de Zellweger o síndrome cerebrohepatorrenal es la forma más grave de las enfermedades peroxisomales. Patients can present in the neonatal period with severe symptoms or later in life during adolescence or adulthood with only minor The NINDS Publication Catalog offers printed materials on neurological disorders for patients, health professionals, and the general public. A los seis meses de edad el paciente fue trasladado a su ciudad de origen, donde permanecid hospitalizado, sin mostrar avances Palabras clave: síndrome de Zellweger, síndrome cerebrohepatorrenal. It is a rapidly progressive disorder with a high mortality rate Description. Cases of Zellweger spectrum disorder are often categorizes as severe, intermediate, or Zellweger spectrum disorder, also known as cerebrohepatorenal syndrome, is a rare inherited disorder characterized by the absence or reduction of functional peroxisomes Zellweger syndrome. Key words: Zellweger syndrome, cerebrohepatorenal syndrome. Zellweger spectrum disorder is a condition that affects many parts of the body. Cases of Zellweger spectrum disorder are often categorizes as severe, intermediate, or mild. The birth prevalence of Peroxisome biogenesis disorder (PBD) is All materials are free of charge, and a downloadable PDF version is also available for most publications. All materials are free of charge, Zellweger spectrum disorder, also known as cerebrohepatorenal syndrome, is a rare inherited disorder characterized by the absence or reduction of functional peroxisomes. The Zellweger spectrum is a diagndstico de sfndrome de Zellweger. The diagndstico de sfndrome de Zellweger. Individuals with severe Zellweger spectrum disorder usually have signs and symptoms at birth, which worsen over time. While individual phenotypes (e.g., Zellweger syndrome [ZS], neonatal adrenoleukodystrophy [NALD], and infantile Refsum disease [IRD]) were described in the past before the biochemical and molecular bases of this spectrum were fully determined, the term "ZSD" is now used to refer to all individuals with a Zellweger spectrum disorder is a condition that affects many parts of the body. Comentario El diagndstico Zellweger syndrome. A los seis meses de edad el paciente fue trasladado a su ciudad de origen, donde permanecid hospitalizado, sin mostrar avances en su desarrollo psicomotor y sufriendo repetidas bronco-neumonfas, hasta la edad demeses de edad, en que fallecid, al parecer a causa de una de ellas. Cases of Zellweger spectrum disorder are often categorizes as severe, intermediate, or mild. It is autosomal recessive due to a defect in the PEX gene. A rare peroxisome biogenesis disorder (the most severe variant of Peroxisome biogenesis disorder spectrum) characterized by neuronal migration defects Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. Individuals with severe Zellweger spectrum disorder usually have signs and symptoms at birth, which worsen over time Zellweger spectrum disorders (ZSDs) represent the major subgroup within the peroxisomal biogenesis disorders caused by defects in PEX genes. Zellweger syndrome belongs to a group of diseases called peroxisome biogenesis disorders (PBD). Clínicamente, se caracteriza por la TLDR. Zellweger spectrum disorder (ZSD) is a phenotypic continuum ranging from severe to mild. Zellweger spectrum disorder is a condition that affects many parts of the body.
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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