DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for SMARCB1-related schwannomatosis — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSMARCB1-related schwannomatosis maps to a 2-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 smarcb1-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
A 2007 study of 21 schwannomatosis patients and eight tumours from four patients found a novel germline SMARCB1 mutation in one patient. In two schwannomas from that patient, inactivating somatic NF2 mutations were present alongside loss of heterozygosity of chromosome 22q. The authors proposed a four-hit mechanism involving both SMARCB1 and NF2 in schwannomatosis tumour formation. A 2022 report described a family with a shared novel SMARCB1 mutation (c.92A>G, p.Glu31Gly) in a proband with generalised painless extradural schwannomatosis and her daughter with segmental painful intradural disease, suggesting intrafamilial phenotypic variability.
A 2015 study measured SMARCB1 expression by qRT-PCR. Expression was downregulated 8-fold in a painful schwannomatosis tumour and 5-fold in a non-painful schwannomatosis tumour, compared to non-schwannomatosis schwannomas and a neurofibroma. Cell lines derived from those tumours showed similar SMARCB1 expression to the parent tumours. A 2024 case report described a 55-year-old woman with an 8-year history of schwannomatosis who carried a sporadic synonymous SMARCB1 single nucleotide polymorphism (c.1032C>T, p.Gly344Gly) not previously linked to the condition. Both her schwannomas showed mosaic loss of nuclear SMARCB1 protein (10% to 60%), and protein assays confirmed low SMARCB1 levels, with marked loss in a distal thigh schwannoma.
A 2020 literature review noted that schwannomatosis is rare, distinct from neurofibromatosis type 2, and that the most common symptom is pain, with spinal and peripheral nerve involvement in most patients. Treatment is conservative if asymptomatic and surgical if symptomatic, with the goal of symptom control and preservation of neurological function. No drug therapy is discussed in any of these abstracts.
What remains missing is any clinical trial of a drug for schwannomatosis, any preclinical drug testing in relevant models, and any systematic patient stratification by SMARCB1 mutation type or tumour location. Funding for drug-repurposing screens or for trials targeting the SMARCB1–NF2 pathway has not been reported.
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 Mutation · 2007 · 183 citations
Evidence of a four-hit mechanism involving<i>SMARCB1</i>and<i>NF2</i>in schwannomatosis-associated schwannomas
AbstractSchwannomatosis is characterized by the onset of multiple intracranial, spinal, or peripheral schwannomas, without involvement of the vestibular nerve, which is instead pathognomonic of neurofibromatosis type 2 (NF2). Recently, a schwannomatosis family with a germline mutation of the SMARCB1 gene on chromosome 22 has been described. We report on the molecular analysis of the SMARCB1 and NF2 genes in a series of 21 patients with schwannomatosis and in eight schwannomatosis-associated tumors from four different patients. A novel germline SMARCB1 mutation was found in one patient; inactivating somatic mutations of NF2, associated with loss of heterozygosity (LOH) of 22q, were found in two schwannomas of this patient. This is the second report of a germline SMARCB1 mutation in patients affected by schwannomatosis and the first report of SMARCB1 mutations associated with somatic NF2 mutations in schwannomatosis-associated tumors. The latter observation suggests that a four-hit mechanism involving the SMARCB1 and NF2 genes may be implicated in schwannomatosis-related tumorigenesis.
British Journal of Neurosurgery · 2020 · 46 citations · open access
What to know about schwannomatosis: a literature review
AbstractBACKGROUND: Schwannomatosis is a relatively rare disorder and is related to neurofibromatosis type 2. Although there is clinical overlap between schwannomatosis and neurofibromatosis type 2, these diseases have to be regarded as separate entities due to the genetic origin and course of the disease. METHODS: A comprehensive review of the literature was conducted for relevant studies using Pubmed and Cochrane databases to discuss the epidemiology, clinical presentation, diagnostic criteria, pathological and imaging features, treatment and genetics of schwannomatosis. RESULTS: gene play a role in the pathophysiology of schwannomatosis. The most common symptom is pain with affection of the spine and peripheral nerves in the majority of patients. High quality contrast enhanced MRI scan is the imaging modality of choice. Treatment is conservative if asymptomatic and surgical if symptomatic. The goal is symptom control with preservation of neurological function. CONCLUSION: Schwannomatosis is a relatively rare disorder in which the main goal is to preserve neurological function.
A Rare Case of Familial Schwannomatosis Showing Intrafamilial Variability with Identification of a Shared Novel Germline SMARCB1 Mutation
AbstractSchwannomatosis is characterized by the presence of multiple schwannomas without landmarks of NF2. It is considered the rarest form of neurofibromatosis (NF). Here, we report the first case of familial schwannomatosis with regard to the segmental/generalized phenotype, in which the proband and the daughter present a distinct phenotype in this classification. The proband presents a generalized, painless, extradural type of schwannomatosis, while the daughter shows a segmental, painful, intradural type of schwannomatosis. Whole-exome sequencing of the affected individuals revealed a shared novel SMARCB1 gene mutation (c.92A > G, p.Glu31Gly) despite the clinical variability. We thus suggest two points in the diagnosis of familial schwannomatosis: The identified novel germline SMARCB1 variant can be reflective of a phenotypical progression from a segmental to a generalized type of schwannomatosis, or an intrafamilial variability in inherited schwannomatosis, which was not reported in previous literature. The specific combination of somatic NF2 mutations may be a major factor in regulating the severity and scope of the resulting phenotype in schwannomatosis.
SMARCB1 expression in Parental Schwannomatosis Tumors.
Abstract<p>qRT-PCR was used to examine expression of SMARCB1 in cell lines and tumors. SMARCB1 expression was downregulated 8 fold in painful schwannomatosis tumor and 5 fold in the non-painful schwannomatosis tumor compared to a non-schwannomatosis schwannomas and a neurofibroma Hnp-SWN-14O and Hp-SWN-14F showed similar expression of SMARCB1 to the parent tumors from which they were derived.</p>
BIOM-47. SINGLE NUCLEOTIDE POLYMORPHISM IN SMARCB1 MUTATION FOR SCHWANNOMATOSIS
AbstractAbstract Schwannomatosis, a form of neurofibromatosis, involves critical roles for the SMARCB1 gene. Clinical diagnosis guidelines recommend considering pathogenic variants or suspecting schwannomatosis to exclude splicing-related intron mutations. However, some patients may initially present with non-significant mutations and lack clinical signs of schwannoma, leading to misdiagnosis, missed annual assessments, malignancy awareness, and genetic consultation opportunities during pregnancy. Here, we reported a patient with a sporadic synonymous mutation in the SMARCB1 gene (SNP c.1032 C&gt;T (p.Gly344Gly(GGC&gt;GGT)) in exon 8), not previously associated with schwannomatosis. This patient, a 55-year-old female with an 8-year history of schwannomatosis, presented to the neurosurgical department for recurrent tumor removal. Initially, the clinical impact of the SMARCB1 mutation was undetermined, and other genes tested were wild-type. Both schwannomas exhibited a mosaic loss of nuclear SMARCB1 protein, ranging from 10% to 60%. Protein assays confirmed low levels of SMARCB1 protein, with a significant loss in the distal thigh schwannoma. It highlights the tumorigenic potential of single nucleotide polymorphism in the SMARCB1 gene and aids clinicians in making more accurate diagnoses in patients with pathologically confirmed schwannoma. It underscores the importance of long-term follow-up, increased awareness of recurrence and malignancy, and timely surgical planning in such patients.
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.
