DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intraneural perineurioma — 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 moduleIntraneural perineurioma 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
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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 intraneural perineurioma 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
KRas proto-oncogene, GTPase (KRAS) — KRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7VVB · 1.7 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
Intraneural perineurioma is a benign, very slow growing peripheral nerve sheath tumour that typically presents insidiously in young people. In a longitudinal study of 32 patients, median age of onset of neurological symptoms was 14 years, and all patients had motor deficits; mild sensory symptoms or signs were experienced by 27 patients, with prickling or numbness in 20, mild pain in 13, and sensory loss in 23. The sciatic nerve or its branches was most commonly affected. A separate retrospective series of 30 patients reported a mean age of 22 years, with 70% showing atrophy, 43% having sensory deficits, and 17% suffering pain. All patients in both series had some degree of motor deficit.
Long-term follow-up indicates the condition is static or only slowly progressive. In the longitudinal study, 23 patients were followed for a median of 36 months; the median Neuropathy Impairment Score changed from 12.6 to 15.4 points, a non-significant difference. Ten patients judged their symptoms unchanged, nine slightly worse, and four slightly better. In the retrospective series of 30 patients, 70% had an MRI within five years postoperatively showing no progress. A dedicated radiological follow-up study of 20 patients with two MRIs at least two years apart found that lesions were on average larger in width on repeat imaging, but by lesion-to-landmark ratio there was no difference in length, and no lesion grew to involve a new nerve or nerve division. None of the radiological changes correlated with clinical progression.
Diagnosis requires targeted fascicular biopsy of the focal nerve enlargement identified by imaging. Complete surgical resection with nerve graft reconstruction is not recommended; results after grafting are poor, possibly because residual tumour cells along the nerve cannot be visualised. In the retrospective series, four patients had complete resection and grafting, but outcomes were not detailed. Malignant transformation has not been reported. The evidence suggests these tumours should not be resected routinely, and a long-distance epineuriotomy to decompress the hypertrophic fascicle may be reasonable.
What remains missing is any prospective trial comparing surgical decompression with observation alone, and any reliable method to predict which patients, if any, will experience meaningful clinical deterioration. The natural history data come from small, retrospective or telephone-interview follow-up studies, and no stratification by age, nerve involved, or initial impairment severity has been tested. No drug therapy has been studied in any of these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 2009 · 138 citations · open access
Longitudinal study of intraneural perineurioma--a benign, focal hypertrophic neuropathy of youth
AbstractThe natural history of intraneural perineurioma has been inadequately studied. The aim of this study was to characterize the clinical presentation, electrophysiologic and imaging features and outcome of intraneural perineurioma. We ask if intraneural perineurioma is a pure motor syndrome that remains confined to one nerve and should be treated by surgical resection. We examined the nerve biopsies of cases labelled perineurioma and selected those with diagnostic features. Thirty-two patients were identified; 16 children and 16 adults; 16 males and 16 females. Median age of onset of neurological symptoms was 14 years (range 0.5-55 years) and median age at evaluation was 17 years (range 2-56 years). All patients had motor deficits; however, mild sensory symptoms or signs were experienced by 27 patients; 'prickling' or 'asleep numbness' in 20, mild pain in 13 and sensory loss in 23. The sciatic nerve or its branches was most commonly affected in 15, followed by brachial plexus, radial nerve and ulnar nerve (four each). Magnetic resonance imaging demonstrated nerve enlargement (29/32), T1 isointensity (27/32), T2 hyperintensity (25/32) and contrast enhancement (20/20). Diagnoses were made based on targeted biopsy of the focal nerve enlargement identified by imaging. Neurological impairment was of a moderate severity (median Neuropathy Impairment Score was 12 points, range 2-49 points). All patients had focal involvement with 27 involving one nerve and five involving a plexus (one bilateral). Long-term follow-up was possible by telephone interview for 23 patients (median 36 months, range 2-177 months). Twelve patients also had follow-up neurologic evaluation (median 45 months, range 10-247 months). The median Neuropathy Impairment Score had changed from 12.6 to 15.4 points (P = 0.19). In all cases, the distribution of neurologic findings remained unchanged. Median Dyck Disability Score was 3 (range 2-5) indicating a mild impairment without interfering with activities of daily living. Ten patients judged their symptoms unchanged, nine slightly worse and four slightly better. We conclude intraneural perineurioma is a benign hypertrophic (non onion bulb) peripheral nerve tumour that presents insidiously in young people and is motor predominant with mild sensory involvement. It is most often a mononeuropathy, but a plexopathy can occur. Diagnosis of this condition requires clinical suspicion, imaging, targeted fascicular biopsy of the lesion and expertise of nerve pathologists. As these tumours are static or slowly progressive, remain confined to their original distribution and have low morbidity, they probably should not be resected routinely. Because intensive evaluation is needed for diagnosis, intraneural perineurioma is probably under-recognized.
Journal of Neurological Surgery Part A Central European Neurosurgery · 2021 · 22 citations
Perineurioma: A Rare Entity of Peripheral Nerve Sheath Tumors
AbstractAbstract Objective Intraneural perineurioma is a rare tumor entity. It is a benign, very slow growing peripheral nerve sheath tumor that typically occurs in children and young adults. Motor deficits and muscle atrophy are classic presenting symptoms, while sensory deficits are rare at the onset of the disease. Recommended treatment strategies are lacking. We have evaluated the clinical follow-up and our experience with treatment of this rare entity. Methods A total of 30 patients with intraneural perineuriomas were assessed retrospectively. Demographic data, clinical symptoms, diagnostic examinations, therapy strategies, and clinical outcome were analyzed. Descriptive statistical methods were used for evaluation. Results The mean age was 22 years. Eleven women and 19 men were affected. The lesion occurred in the area of the upper extremity in 16 patients and in the area of the lower extremity in 14 patients. The most frequently affected nerve was the sciatic nerve, followed by the radial nerve. All patients showed a motor deficit to some extent. Seventy percent (n = 21) revealed atrophy, 43.3% (n = 13) had sensitive deficits, and 17% (n = 5) suffered of pain. Fascicle biopsies were performed in 26 patients (87%). In four patients (13%), the tumor was completely resected and then reconstructed via nerve grafts. Seventy percent of the patients (n = 21) received a magnetic resonance imaging (MRI) within 5 years postoperatively, in which no progress was shown. Conclusions To diagnose perineurioma, it is essential to take a biopsy of an enlarged, nonfunctional fascicle. Furthermore, a long-distance epineuriotomy to decompress the hypertrophic fascicle is reasonable. To preserve the nerves' residual function, a complete resection is not recommended. Results after grafting are poor. One reason for this might be residual tumor cells along the nerve that cannot be visualized. Malignant transformation is not yet reported and tumor growth is stable for years.
Clinical and Radiological Follow-up of Intraneural Perineuriomas
AbstractBACKGROUND: Management of intraneural perineuriomas remains controversial, largely due to the lack of knowledge regarding the natural history of these lesions. OBJECTIVE: To describe the typical radiological growth pattern of intraneural perineuriomas and to determine how the pattern of growth relates to clinical progression. METHODS: We performed a retrospective review of the magnetic resonance imaging (MRI) studies and serial clinical examinations of a cohort of patients with biopsy-proven intraneural perineuriomas who had 2 MRI studies at least 2 yr apart. The outcome of interest was radiological growth in length or width of the intraneural perineurioma. Radiological growth was tested for association with clinical progression. RESULTS: Twenty patients were included in the study. By width, the lesions were on average larger on repeat imaging (P = .009). By absolute length, the lesions were on average longer on repeat imaging (P = .02). By lesion:landmark ratio, there was no difference in length of the lesions between sequential images (P = .09), with 10 (50%) lesions being shorter and 7 (35%) showing no change. No lesions grew to involve a new nerve or division of a nerve on sequential imaging. None of the variables tested were associated with clinical progression. CONCLUSION: We found that intraneural perineuriomas only rarely grow in length, do not grow to involve new nerves or nerve divisions, and growth does not correlate with clinical progression. These findings have significant ramifications for management of these tumors.
Case Reports in Clinical Radiology · 2023 · 0 citations · open access
Unusual case of mononeuropathy in child: Intraneural perineurioma of sciatic nerve
AbstractIntraneural perineurioma is a benign nerve sheath tumor of the perineurium characterized by focal perineural cell proliferation. It is primarily seen in young adults. Early childhood presentation is uncommon. We present this interesting case in a child with overall clinical assessment, nerve conduction tests, and magnetic resonance findings in keeping with intraneural perineurioma of the sciatic nerve. It is essential to recognize this potentially treatable disease entity in the early childhood and exclude other causes of nerve palsy.
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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