DeCure for Peroxisome biogenesis disorder 7A (Zellweger)
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for peroxisome biogenesis disorder 7A (Zellweger) — 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 modulePeroxisome biogenesis disorder 7A (Zellweger) 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 peroxisome biogenesis disorder 7a (zellweger) 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
Peroxisome biogenesis disorders are autosomal recessive conditions in which peroxisome assembly is impaired, leading to deficiencies of peroxisomal enzymes, complex developmental sequelae and progressive disabilities. The cellular hallmark of Zellweger syndrome is failure to assemble normal peroxisomes. Mutations in 13 PEX genes encoding peroxins have been identified in patients with peroxisomal biogenesis disorders. For most patients there is a correlation between clinical severity and the effect of the mutation on PEX protein function. Mutations in PEX13 are among the least common causes, with only three mutations reported before 2009. Two infants with classical Zellweger syndrome were assigned to complementation group H and found to harbour two novel PEX13 mutations: one patient had a genomic rearrangement resulting in a 147 kb deletion spanning the whole of PEX13, the other had an out-of-frame deletion of 14 bp. That was the first report of a PEX13 deletion.
The peroxisome biogenesis disorders are divided into two main groups: Zellweger spectrum disorder, due to defects in any one of 13 PEX genes, and Rhizomelic Chondrodysplasia Punctata spectrum, mainly due to defects in PEX7. Zellweger syndrome, neonatal adrenoleukodystrophy, and infantile Refsum disease form a spectrum of diseases with overlapping features. Diagnosis relies on biochemical measurements of peroxisome metabolites and enzymatic functions, PEX gene sequencing, and in some cases analysis of peroxisome morphology. Recent advancements in diagnosis have expanded the observed phenotypes, indicating that the full spectrum of these disorders remains to be identified.
There are no targeted therapies. The ultimate goals of research are to identify all genes required for peroxisome biogenesis and to understand how their protein products interact to produce normal peroxisomes. Attainment of these goals is expected to lead to a better understanding of the pathophysiology and treatment of peroxisome biogenesis disorders. Improved knowledge of peroxin functions, continued characterisation of disease models, and systematic clinical studies are expected to impact treatment in the near future.
What is still missing is any therapy that has been tested in patients with peroxisome biogenesis disorder 7A. No drug repurposing data, no clinical trial results, and no survival or response rate numbers exist for this specific PEX13-deficient subgroup. The field lacks systematic clinical studies, patient stratification by genotype, and funding for trials in a very rare disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Molecular Genetics · 1995 · 285 citations
Disorders of peroxisome biogenesis
AbstractThe peroxisome is a ubiquitous, subcellular organelle containing more than 50 matrix enzymes that participate in a diverse array of metabolic pathways. Failure to assemble normal peroxisomes is the cellular hallmark of Zellweger syndrome and other human disorders of peroxisome biogenesis. Identification of the genes required for peroxisome biogenesis is proceeding at a rapid pace helped immeasurably by work in other species, particularly various yeasts. The ultimate goals of this effort are to identify all of these genes and to understand how their protein products interact to produce normal appearing and functioning peroxisomes. Attainment of these goals will lead to a better understanding of the peroxisome biogenesis disorders, their pathophysiology and treatment.
American journal of diseases of children · 1988 · 36 citations
Peroxisomal Disorders
AbstractThe peroxisomal disorders are a group of inherited metabolic diseases with serious clinical sequelae. The number of recognized peroxisomal disorders has increased substantially since 1973, when an absence of peroxisomes was observed in patients with the cerebro-hepato-renal (Zellweger's) syndrome. More subtle peroxisomal dysfunction is now recognized, including that deriving from single peroxisomal enzymes. Peroxisomal disorders are relatively rare. However, these disorders assume importance because of our growing ability to relate clinical sequelae to specific enzymatic and biochemical deficits, because some of these disorders can now be identified prenatally and their recurrence can be prevented, and because therapies are rapidly evolving. We reviewed these disorders in light of increasing understanding of the biochemistry of the peroxisome.
American Journal of Medical Genetics Part A · 2009 · 18 citations
Zellweger syndrome caused by PEX13 deficiency: Report of two novel mutations
AbstractPeroxisomal biogenesis disorders represent a group of genetically heterogeneous conditions that have in common failure of proper peroxisomal assembly. Clinically, they are characterized by a spectrum of dysmorphia, neurological, liver, and other organ involvement. To date, mutations in 13 PEX genes encoding peroxins have been identified in patients with peroxisomal biogenesis disorders. Mutations in PEX13, which encodes peroxisomal membrane protein PEX13, are among the least common causes of peroxisomal biogenesis disorders with only three mutations reported so far. Here, we report on two infants whose clinical and biochemical profile was consistent with classical Zellweger syndrome and whose complementation analysis assigned them both to group H of peroxisomal biogenesis disorders. We show that they harbor two novel mutations in PEX13. One patient had a genomic rearrangement resulting in a 147 kb deletion that spans the whole of PEX13, while the other had an out-of-frame deletion of 14 bp. This represents the first report of a PEX13 deletion and suggests that further work is needed to examine the frequency of PEX13 mutations among Arab patients with peroxisomal biogenesis disorders.
AbstractThe peroxisome biogenesis disorders (PBD) are a heterogeneous group of autosomal recessive disorders in which peroxisome assembly is impaired, leading to deficiencies of peroxisomal enzymes, complex developmental sequelae and progressive disabilities. Mammalian peroxisome assembly involves the coordinated action of multiple PEX proteins, or peroxins, encoded by PEX genes. There are two main groups of PBD: Zellweger spectrum disorder, due to defects in any one of 13 PEX genes, and Rhizomelic Chondrodysplasia Punctata spectrum, mainly due to defects in PEX7. For most patients, there is a correlation between clinical severity and effect of the mutation on PEX protein function. Diagnosis relies on biochemical measurements of peroxisome metabolites and enzymatic functions, PEX gene sequencing and, in some cases, analysis of peroxisome morphology and more detailed studies of peroxisome biology. Recent advancements in diagnosis have expanded the phenotypes observed, indicating that the full spectrum of these disorders remains to be identified. Although there are no targeted therapies, improved knowledge of peroxin functions, continued characterization of disease models, and systematic clinical studies are expected to impact treatment in the near future.
AbstractA group of conditions characterized by impairment of peroxisome assembly and metabolic pathways confined to this organelle, caused by mutation(s) in the peroxin (PEX) gene family.Phenotypically, they manifest as Zellweger syndrome (ZS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and rhizomelic chondrodysplasia punctata (RCDP1), the latter a distinct peroxisome biogenesis disorder phenotype.ZS, NALD, and IRD have multiple complementation groups and form a spectrum of diseases with overlapping features.
PARIPEX-INDIAN JOURNAL OF RESEARCH · 2023 · 0 citations · open access
A CASE REPORT OF ZELLWEGER SYNDROME WITH GLOBAL DEVEOPMENTAL DELAY
AbstractPeroxisome biogenesis disorder are related to spectrum of genetic diseases that range from severe Zellweger syndrome to milder infantile Refsum disease. Zellweger syndrome is characterized by dysmorphic features, severe hypotonia, seizures, failure to thrive, liver dysfunction and skeletal defects. We report a case of Zellweger syndrome, confirmed by clinical, biochemical and molecular findings, diagnosed in context of dysmorphism, and seizures
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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