DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for NF2-related schwannomatosis — 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 moduleNF2-related schwannomatosis 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 nf2-related schwannomatosis 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
NF2, moesin-ezrin-radixin like (MERLIN) tumor suppressor (NF2) — NF2 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.
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RCSB Protein Data Bank · entry 6CDS · 2.62 Å · ligand [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate (PIO). Experimental structure, not a prediction.
What the evidence adds up to
Neurofibromatosis type 2 (NF2) is a tumour suppressor syndrome that causes bilateral vestibular schwannomas, meningiomas, and ependymomas, leading to major neurologic morbidity. The overall survival rate is estimated at 38% at 20 years from diagnosis. Current treatments are surgery or radiosurgery, but radiation may induce secondary tumours in NF2, and surgery is limited when tumour load is high or tumours are located where resection would cause neurological complications. Avastin is effective only in a fraction of patients. There are no FDA-approved biologic therapies for NF2.
A phase 0 trial tested sorafenib, an oral cRAF/VEGFR-2/PDGFRβ inhibitor, in five adult NF2 patients with peripheral schwannomas. The trial aimed to determine whether molecular target inhibition occurs with oral sorafenib and whether target inhibition in plasma could act as a biomarker. The per-protocol minimal recruitment target depended on a pharmacodynamic response rate of two out of three or three out of five patients. The abstract does not report whether this target was met, nor does it give response rates or survival data for the five patients.
Schwannomatosis is a clinical entity distinct from NF2. In a series of seven patients (five men, two women, mean age 54) with at least two cutaneous schwannomas, no vestibular schwannoma or central nervous system tumour was found on MRI in six patients. Spinal imaging in six patients was normal in five and showed a spinal schwannoma in the sixth. Four patients had hypacusis, but auditory brainstem responses showed no retrocochlear involvement. The authors strictly eliminated the diagnosis of NF2 in these patients.
The Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration has worked since 2011 to develop standardised outcome measures for clinical trials in NF1, NF2, and schwannomatosis, but effective medical treatments remain limited. What is still missing is a proven systemic therapy that improves survival or hearing preservation in a substantial proportion of NF2 patients. The phase 0 sorafenib trial was too small to assess efficacy, and no later-phase trial data are provided. Patient stratification by tumour type, mutation, or age of onset may be needed to detect benefit in a heterogeneous disease, but no such stratification has been validated in a completed trial.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Dermatology · 2009 · 38 citations
Schwannomatosis: A Clinical Entity Distinct from Neurofibromatosis Type 2
AbstractBACKGROUND: Schwannomatosis includes multiple cutaneous schwannomas, central nervous system tumors and various neurologic deficits. OBJECTIVE: To specify the clinical presentation of schwannomatosis, excluding neurofibromatosis type 2 (NF2). METHODS: Patients with at least 2 cutaneous schwannomas were evaluated for NF2 criteria. RESULTS: 5 men and 2 women (mean age 54 +/- 18 years) we included. Two cases were familial. Cutaneous schwannomas were tender nodules with onset above the age of 30 years. Four patients had paresthesias. Four patients had hypacusis, but auditory brainstem responses showed no retrocochlear involvement. No vestibular schwannoma or central nervous system tumor was found with magnetic resonance imaging in 6 patients. Spinal imaging performed in 6 patients was normal in 5 and showed a spinal schwannoma in the 6th patient. CONCLUSION: We strictly eliminated the diagnosis of NF2 in our patients. Exclusion of NF2 in suspected schwannomatosis is essential for further molecular genetic studies.
Journal of Neurology Neurosurgery & Psychiatry · 2019 · 9 citations · open access
Phase 0 trial investigating the intratumoural concentration and activity of sorafenib in neurofibromatosis type 2
AbstractSchwannomas, meningiomas and ependymomas are tumours of the nervous system which occur sporadically or as part of the hereditary disease neurofibromatosis type 2 (NF2). Mutations in neurofibromin 2/NF2 gene cause all NF2-related schwannomas, meningiomas and ependymomas, 77% sporadic schwannomas, 60% sporadic meningiomas and 30% sporadic ependymomas.1 Schwannomas are the hallmark of NF2 and develop in all patients with NF2. Current treatments for NF2-related tumours are surgery or radiosurgery. Radiation may induce additional mutations and formation of secondary tumours in NF2 whereas surgery has limited use in patients with high tumour load or tumours located at the sites where resection would cause neurological complications.2 Avastin is effective but only in a fraction of patients.2 Published consensus recommendations suggest that the development of effective therapies for NF2 is urgent, with great potential for clinical progress.2
Platelet-derived growth factor receptor β (PDGFRβ) is overexpressed and activated in human primary schwannoma cells leading to increased proliferation.3 Using orally available, Food and Drug Administration (FDA)-approved cRAF/VEGFR-2/PDGFRβ inhibitor, sorafenib, this was successfully inhibited in vitro.3
Here we report an open-label, phase 0, single-agent trial (EudraCT: 2011-001789-16, REC: 11/LO/0771) testing sorafenib in patients with NF2 with the aim to determine whether molecular target inhibition occurs with oral sorafenib in patients with NF2 and whether target inhibition in plasma with oral sorafenib in patients with NF2 can act as a biomarker.
Per protocol minimal recruitment target depending on the pharmacodynamic (PD) response rate was three patients (two out of three or three out of five with 60% PD response).4 Here, five adult patients with NF2 with peripheral schwannomas (PS), diagnosed according to National Institute of Health (NIH) Diagnostic Criteria for NF, were treated with sorafenib administered orally at maximum tolerated dose (MTD) of 400 mg, two times a day, for 10 …
AbstractNeurofibromatosis (NF) type 1 (NF1), NF type 2 (NF2), and schwannomatosis are genetic tumor predisposition syndromes with a wide variety of clinical manifestations. Effective medical treatments for these conditions remain limited. Since its founding in 2011, the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration has worked to develop standardized, practical, and clinically meaningful outcome measures for clinical trials in these conditions. Two previous supplements published in Neurology ® in 20131 and 20162 set forth a variety of recommendations that are summarized in the table.
IntechOpen eBooks · 2020 · 0 citations · open access
Neurofibromatosis Type 2: Current Trends and Future Directions for Targeted Biologic Therapies
AbstractNeurofibromatosis type 2 (NF2) is an inherited tumor predisposition syndrome leading to the formation of vestibular schwannomas (VS) and other central nervous system (CNS) tumors. Clinical NF2 follows a genetic alteration to the NF2 gene, which disrupts the function of a cell membrane-related protein, merlin. Though the role of merlin is incompletely understood, it is predominantly thought to achieve tumor suppressive effects by affecting multiple signaling pathways important for contact inhibition, cellular proliferation, and cellular growth. Patients with NF2 have a bimodal age of onset in children and young adults, with the former tending to present with a more severe phenotype involving multiple tumors. Currently available treatments are non-curative. Surgical resection is the mainstay for growing tumors but comes at the cost of significant morbidity, while radiotherapy is generally not advisable due to the risk of secondary malignancy and malignant transformation. Hence, there remains a critical demand for effective anti-neoplastic therapies for NF2-related tumors. There are currently no FDA-approved biologic therapies for the treatment of NF2. Given the complexity and far-reaching effects of Merlin, multiple molecular targets and pathways have been investigated and are currently at various stages of investigation.
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.
