DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Perrault syndrome — 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 modulePerrault syndrome 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 perrault 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
caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) — CLPP 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 diodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1TG6 · 2.1 Å · ligand 1,4-DIETHYLENE DIOXIDE (DIO). Experimental structure, not a prediction.
What the evidence adds up to
In two families with Perrault syndrome, whole-exome sequencing identified compound heterozygous mutations in the C10orf2 gene, which encodes Twinkle primase-helicase. One Japanese family carried p.Arg391His and p.Asn585Ser; one European family carried p.Trp441Gly and p.Val507Ile. Twinkle is essential for mitochondrial DNA replication, and the same gene is known to cause dominant progressive external ophthalmoplegia type 3 and recessive mitochondrial DNA depletion syndrome 7 (infantile-onset spinocerebellar ataxia). The 2014 study concluded that these Twinkle mutations expand the phenotypic spectrum of recessive Twinkle disease and that both phenotypic and genetic heterogeneity in Perrault syndrome require genomic definition.
Perrault syndrome was first described in 1951. It is a rare genetic disorder characterised by sensorineural hearing loss in both sexes and ovarian dysgenesis in females. Neurologic deficits develop gradually, and patients are often misdiagnosed with other neurological disease early in life. A 2023 case report of genetically diagnosed Perrault syndrome 5 (caused by TWNK variants) reiterates this pattern. The 2022 review lists five genes in which mutations cause Perrault syndrome: TWNK, CLPP, HARS2, LARS2, and HSD17B4.
No treatment or clinical trial data are reported in any of these abstracts. No survival rates, response rates, or sample sizes beyond the two families and one single case are given. The abstracts do not describe any intervention or outcome measure.
What is still missing is any prospective natural history study that tracks neurologic decline alongside hearing and ovarian function, a standardised diagnostic criteria set that accounts for the genetic and phenotypic heterogeneity, and funding for a clinical trial platform that could test therapies once the underlying mitochondrial or proteostatic mechanisms are better understood. Patient stratification by genotype will be necessary before any intervention can 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.
Neurology · 2014 · 108 citations · open access
Mutations in Twinkle primase-helicase cause Perrault syndrome with neurologic features
AbstractOBJECTIVE: To identify the genetic cause in 2 families of progressive ataxia, axonal neuropathy, hyporeflexia, and abnormal eye movements, accompanied by progressive hearing loss and ovarian dysgenesis, with a clinical diagnosis of Perrault syndrome. METHODS: Whole-exome sequencing was performed to identify causative mutations in the 2 affected sisters in each family. Family 1 is of Japanese ancestry, and family 2 is of European ancestry. RESULTS: In family 1, affected individuals were compound heterozygous for chromosome 10 open reading frame 2 (C10orf2) p.Arg391His and p.Asn585Ser. In family 2, affected individuals were compound heterozygous for C10orf2 p.Trp441Gly and p.Val507Ile. C10orf2 encodes Twinkle, a primase-helicase essential for replication of mitochondrial DNA. Conservation and structural modeling support the causality of the mutations. Twinkle is known also to harbor multiple mutations, nearly all missenses, leading to dominant progressive external ophthalmoplegia type 3 and to recessive mitochondrial DNA depletion syndrome 7, also known as infantile-onset spinocerebellar ataxia. CONCLUSIONS: Our study identifies Twinkle mutations as a cause of Perrault syndrome accompanied by neurologic features and expands the phenotypic spectrum of recessive disease caused by mutations in Twinkle. The phenotypic heterogeneity of conditions caused by Twinkle mutations and the genetic heterogeneity of Perrault syndrome call for genomic definition of these disorders.
Journal of Neuroscience and Neurological Research · 2022 · 2 citations · open access
The Role of Mutations on Genes TWNK, CLPP, HARS2, LARS2, HSD17B4 in Perrault Syndrome
AbstractPerrault syndrome was first reported by Dr. M. Perrault, a physician from Paris, in 1951. Perrault syndrome is a rare genetic disease that causes various signs and symptoms in men and women affected by this syndrome. One of the key features of this syndrome is hearing loss, which occurs in both men and women. In perrault syndrome, hearing problems occur due to changes in the inner ear, known as hearing loss. This disorder usually affects both ears of the patient and the first symptoms can start at birth or in infancy. Perrault syndrome has several genetic causes. However, researchers believe that perrault syndrome is caused by mutations in the TWNK, CLPP, HARS2, LARS2, and HSD17B4 genes.
Journal of the Korean Neurological Association · 2023 · 0 citations · open access
<i>TWNK</i> Gene Associated Perrault Syndrome Patient with Neurological Features
AbstractPerrault syndrome 5 is a rare autosomal recessive disorder that is characterized by the association of sensorineural hearing loss and ovarian dysgenesis in females with diversity of neurologic deficits due to variants of twinkle mtDNA helicase (<i>TWNK</i>) gene. Since neurologic deficits develop gradually, patient is often misdiagnosed with other neurological disease during early age. Herein, we report a case of genetically diagnosed Perrault syndrome 5.
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.
