DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for neurofibromatosis, familial spinal — 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 moduleNeurofibromatosis, familial spinal 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 neurofibromatosis, familial spinal 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
neurofibromin 1 (NF1) — NF1 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 1sdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7PGU · 3.3 Å · ligand (1S)-2-{[(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-1-[(PALMITOYLOXY)METHYL]ETHYL STEARATE (PEV). Experimental structure, not a prediction.
What the evidence adds up to
Spinal neurofibromatosis (SNF) is a distinct form of NF1 defined by bilateral neurofibromas involving all spinal roots, with few or no cutaneous manifestations. A 2014 review of 98 published SNF cases identified 49 patients meeting strict criteria (21 males, 28 females; aged 4–74 years), including 9 families and 27 sporadic cases. Café-au-lait spots occurred in only 67% of SNF patients versus 56% in patients with neurofibromas of multiple but not all spinal roots (MNFSR). Other NF1 features were less frequent in both groups. Missense mutations in the NF1 gene were significantly more common in SNF than in classical NF1 (odds ratio 6.16; p = 0.0001). A 2020 study of 19 NF1 families with at least one SNF member, 37 sporadic SNF patients, and 100 classical NF1 patients confirmed a higher proportion of missense mutations in SNF (21% versus 8%; p = 0.016; OR 3.13) and a lower proportion of nonsense mutations (12.5% versus 28%; p = 0.026; OR 0.36). The same study also identified rare damaging variants in RAS pathway genes and neurofibromin interactors (LIMK2, RASAL1, RASAL3, SOS1, A2ML1, MAP3K1) in multiple SNF cases, suggesting these may act as modifier genes.
Two 1992 abstracts describe clinical features and genetic linkage analysis of two pedigrees with familial spinal neurofibromatosis, but provide no numerical data. A 2015 German questionnaire study collected 17 patients with suspected familial spinal neurofibromatosis (15 unpublished; 9 women, 7 men; aged 24–78) and proposed diagnostic criteria for the first time. No treatment data, survival figures, or response rates appear in any of these abstracts.
The natural history of SNF remains poorly quantified. No clinical trial data exist for any drug in this population. The genetic associations — particularly missense NF1 mutations and potential modifier genes — suggest possible targets, but no interventional studies have been conducted. What is missing is a prospective natural history study with standardised imaging and clinical endpoints, funding for a multi-centre trial, and any attempt to stratify patients by genotype before testing a therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Genetics · 2014 · 93 citations
The natural history of spinal neurofibromatosis: a critical review of clinical and genetic features
AbstractSpinal neurofibromatosis (SNF) is a related form of neurofibromatosis 1 (NF1), characterized by bilateral neurofibromas (histologically proven) of all spinal roots (and, eventually, of all the major peripheral nerve branches) with or without other manifestations of classical NF1. By rigorous application of these criteria to the 98 SNF cases published, we developed: (i) a cohort of 49 SNF patients (21 males and 28 females; aged 4-74 years]: 9 SNF families (21/49), 1 mixed SNF/NF1 family (1/49) and 27 of 49 sporadic SNF patients (including 5 unpublished patients in this report); and (ii) a group of 49 non-SNF patients including: (a) 32 patients with neurofibromas of multiple but not all spinal roots (MNFSR): 4 mixed SNF/MNFSR families (6/32); (b) 14 patients with NF1 manifestations without spinal neurofibromas, belonging to SNF (8/49) or MNFSR families (6/32); (c) 3 patients with neurofibromas in one spinal root. In addition to reduced incidence of café-au-lait spots (67% in SNF vs 56% in MNFSR), other NF1 manifestations were less frequent in either cohort. Molecular testing showed common NF1 gene abnormalities in both groups. The risk of developing SNF vs NF1 was increased for missense mutations [p = 0.0001; odds ratio (OR) = 6.16; confidence interval (CI) = 3.14-13.11], which were more frequent in SNF vs MNFSR (p = 0.0271).
AbstractThe clinical features and genetic linkage analysis of two pedigrees with familial spinal neurofibromatosis (NF) are described from the Divisions of Neurology and Medical Genetics, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Neurofibromatosis Institute, Pasadena, CA; and Department of Medical Informatics, University of Utah, Salt Lake City, UT.
Galter Health Sciences Library, Northwestern University · 1992 · 0 citations · open access
Familial Spinal Neurofibromatosis
AbstractThe clinical features and genetic linkage analysis of two pedigrees with familial spinal neurofibromatosis (NF) are described from the Divisions of Neurology and Medical Genetics, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA; the Neurofibromatosis Institute, Pasadena, CA; and Department of Medical Informatics, University of Utah, Salt Lake City, UT.
OPen Access Repositorium der Universität Ulm (OPARU) (Ulm University) · 2015 · 0 citations · open access
Klinik und Genetik der Familiären Spinalen Neurofibromatose
AbstractFamilial Spinal Neurofibromatosis (FSNF) is a rare type of neurofibromatosis. Only a few clinical cases have been published worldwide. To collect data about the clinical appearance and the genetics we have sent a self-made questionnaire to patients with expected FSNF from the neurofibromatosis ambulance of the University of Ulm. Questionnaires have also sent to institutes for human genetics and neurosururgical departments throughout Germany. It has been possible to record 17 patients with expected FSNF of which 15 have not been published before. Finally we have got the incidence of FSNF and diagnostic criteria for patients with FSNF have been suggested for the first time. Our population has included 9 women and 7 men aged from 24 to 78.
BIOM-10. PREVALENCE OF NF1 MISSENSE MUTATIONS AND CANDIDATE MODIFIER GENES IN SPINAL NEUROFIBROMATOSIS PATIENTS
AbstractAbstract INTRODUCTION Spinal Neurofibromatosis (SNF), a distinct clinical entity of NF1, characterized by bilateral neurofibromas involving all spinal roots and a few, if any, cutaneous manifestations, entails greater morbidity than the classical form of disease. Nevertheless, there are no reliable patterns to sort out patients at risk for developing SNF. MATERIALS AND METHODS We investigated 19 NF1 families with at least one SNF member, 37 sporadic SNF patient and 100 NF1 patients with classical form of disease. We applied Targeted NGS using a panel consisting of 139 genes encoding RAS pathway effectors, neurofibromin interactors and genes mapping at 17q11.2 region. RESULTS In SNF patients we found a higher percentage of missense (21% versus 8%, p=0 0.016, OR 3.13 (95% CI 01.1 -8.2) and a lower percentage of nonsense NF1 mutations (12.5% versus 28%,, p= 0.026, OR 0.36 (95% CI 0.14–0.9) than in classical NF1 cases. Furthermore, we evaluated rare variants with damaging potential predictors in genes of the RAS pathway and in neurofibromin interactors. In more than one sporadic case possible pathogenic variants were found in LIMK2 (neurofibromin interactor), RASAL1, RASAL3, SOS1, A2ML1, MAP3K1 (RAS pathway effectors), while in more than one SNF family were detected RASAL1, RASAL3, MAP3K1 genes variations. CONCLUSIONS Our results confirm the correlation between NF1 genotype and SNF phenotype as previously reported (Ruggieri, 2015), suggesting that neurofibromin gain-of-functions mutations are associated to SNF. In some patients, the co-occurrence of potential pathogenic variants in NF1 related genes with severe phenotypes was detected supporting their role as modifier genes and promising therapeutic targets.
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.
