DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for primary progressive multiple sclerosis — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePrimary progressive multiple sclerosis maps to a 6-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 primary progressive multiple sclerosis 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
Bruton tyrosine kinase (BTK) — BTK 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 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
Primary progressive multiple sclerosis accounts for 10% to 15% of all MS cases and is defined by insidious progression from onset, making it clinically distinct from relapsing remitting MS. Diagnosis is often delayed or mistaken, and as of 2010 no effective treatments were known. A 2013 review noted that the disorder presents great difficulties for management and that difficult hurdles remain, though it also offers opportunities for understanding progressive disability in MS.
A 1996 study measured soluble E-selectin, a marker of endothelial activation, in 28 MS patients and 10 controls. Primary progressive patients had significantly higher sE-selectin concentrations (22.2 ng/ml, SD 6.1) compared to relapsing remitting (9.8 ng/ml, SD 2.1) and secondary progressive patients (7.7 ng/ml, SD 2.7, P=0.03). This elevation was driven by five of the ten primary progressive patients, who had persistently raised sE-selectin despite relatively inactive MRI scans. No correlation was found between sE-selectin and gadolinium enhancement on MRI, but sE-selectin correlated closely with TNF-alpha (r=0.71, P<0.001). Primary progressive patients had normal C-reactive protein concentrations (1.03 mg/l, SD 1.14), significantly lower than relapsing remitting (3.16 mg/l, SD 2.54) and secondary progressive patients (2.28 mg/l, SD 2.1, P=0.03). Raised CRP correlated with infections, clinical relapse, and gadolinium enhancement. Von Willebrand factor was normal in all groups.
A 2019 prospective study of 178 patients in routine clinical practice examined high-dose biotin in progressive MS. The supplementary table from that study is referenced but the abstract itself provides no numerical results on outcomes such as disability progression or response rates.
What remains missing is any proven treatment for primary progressive MS. No large randomised controlled trial has shown a drug to slow disability progression in this phenotype. The biological differences between primary progressive and relapsing forms are increasingly documented but have not yet translated into a therapy. Adequately powered trials with careful patient stratification, and the funding to conduct them, are still needed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Neurology Neurosurgery & Psychiatry · 2013 · 72 citations · open access
Primary progressive multiple sclerosis: progress and challenges
AbstractPrimary progressive multiple sclerosis (MS) has long been recognised as presenting great difficulties to our management of what is increasingly a treatable neurological disease. Here we review some basic and clinical aspects of primary progressive MS, and describe how the disorder in fact offers powerful insights and opportunities for better understanding multiple sclerosis, and from a practical perspective an invaluable clinical substrate for studying and treating progressive disability in MS. Difficult hurdles remain, however, and these too are reviewed.
Journal of Neurology Neurosurgery & Psychiatry · 1996 · 66 citations · open access
Soluble E-selectin in multiple sclerosis: raised concentrations in patients with primary progressive disease.
AbstractOBJECTIVE: To determine whether concentrations of soluble E-selectin (sE-selectin), an immunological marker of endothelial activation, were correlated with gadolinium-DPTA enhancement on MRI in patients with multiple sclerosis. METHODS: Serial sE-selectin concentrations were measured in 28 patients with multiple sclerosis undergoing monthly gadolinium (Gd) enhanced MRI of the brain and spinal cord, and in 10 control subjects. C reactive protein (CRP), von Willebrand factor (vWF), and tumour necrosis factor-alpha (TNF alpha) were also determined. RESULTS: Primary progressive patients had significantly increased sE-selectin concentrations compared with the relapsing remitting and secondary progressive patients who had normal sE-selectin concentrations (22.2 (SD1 6.1) ng/ml v 9.8 (SD2.1) ng/ml and 7.7 (SD2.7) ng/ml, respectively, P = 0.03). This difference was attributable to five of the 10 primary progressive patients who had persistently raised sE-selectin concentrations, with relatively inactive MRI studies. No correlation could be found between sE-selectin concentrations and Gd enhancement on MRI, but a close correlation existed between mean concentrations of sE-selectin and TNF alpha (r = 0.71, P < 0.001). Despite raised sE-selectin and TNF alpha concentrations, primary progressive patients had normal CRP concentrations (1.03 (SD1.14) mg/l), which were significantly lower than the relapsing remitting (3.16 (SD2.54) mg/l) and secondary progressive patients (2.28 (SD2.1) mg/l, P = 0.03). Raised CRP concentrations did correlate with infectious episodes, clinical relapse, and Gd enhancement, and were significantly raised when no MRI activity was found. Concentrations of vWF were normal in all patient groups. CONCLUSIONS: The results further high-light the differences between patients with primary progressive and those with relapsing remitting/secondary progressive multiple sclerosis.
CONTINUUM Lifelong Learning in Neurology · 2010 · 5 citations
PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS
AbstractPrimary progressive multiple sclerosis (MS), comprising 10% to 15% of all cases of MS, is characterized by an insidious progression from the onset of disease, making it clinically distinct from the commonest form, relapsing remitting MS. Making the diagnosis can be challenging, and misdiagnosis and delay in diagnosis are common. Although no effective treatments are currently known, insights into the pathogenesis of this phenotype aid in understanding the processes that drive progression in all forms of MS.
INDIGO (University of Illinois at Chicago) · 2019 · 0 citations · open access
MSJ894713_supplementary_table – Supplemental material for High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice
AbstractSupplemental material, MSJ894713_supplementary_table for High-dose biotin in progressive multiple sclerosis: A prospective study of 178 patients in routine clinical practice by Laura Couloume, Laetitia Barbin, Emmanuelle Leray, Sandrine Wiertlewski, Emmanuelle Le Page, Anne Kerbrat, Solenn Ory, Damien Le Port, Gilles Edan, David-Axel Laplaud and Laure Michel in Multiple Sclerosis Journal
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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