DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for chronic progressive multiple sclerosis — screening already-approved drugs against its 16-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChronic progressive multiple sclerosis maps to a 16-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 chronic 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
In a 1996 study of 28 multiple sclerosis patients, those with primary progressive disease had significantly higher concentrations of soluble E-selectin (mean 22.2 ng/ml) compared with relapsing-remitting (9.8 ng/ml) and secondary progressive patients (7.7 ng/ml). This elevation was driven by five of the ten primary progressive patients, who also had relatively inactive MRI scans. No correlation was found between sE-selectin and gadolinium enhancement on MRI, but a close correlation existed between sE-selectin and tumour necrosis factor-alpha. Despite raised sE-selectin and TNF-alpha, primary progressive patients had normal C reactive protein concentrations (mean 1.03 mg/l), significantly lower than the other groups. The authors concluded that these results highlight differences between primary progressive and relapsing-remitting or secondary progressive multiple sclerosis.
A 2011 review of 100 patients at a VA spinal cord injury division noted that the majority had progressive disease, Expanded Disability Status Scale scores above 6, and extensive medical complications. Many were being treated with disease-modifying agents that the authors stated lack efficacy in progressive disease. The authors suggested these drugs be discontinued and resources directed toward symptomatic treatment, rehabilitation, and management of medical complications until drugs with proven efficacy become available.
A 2022 case report described a 39-year-old woman with relapsing-remitting multiple sclerosis, postpartum onset and aggressive course, who had suboptimal response to alemtuzumab and ocrelizumab. She then received combination treatment with outpatient periodic plasmapheresis every three weeks as maintenance therapy. The report states good tolerance and clinical stability, with no new hospital admissions for acute attacks from February 2020 to March 2021. The authors noted that more specific studies are needed.
Two additional abstracts are general reviews. One from 2000 summarises progress in therapy for relapsing-remitting and secondary progressive multiple sclerosis. Another from 2015 describes the three categories of MS treatment: prevention of relapses and progression, treatment of individual relapses, and symptomatic treatment. Neither provides new trial data for chronic progressive multiple sclerosis. What remains missing are adequately powered randomised controlled trials specifically for primary progressive multiple sclerosis, validated biomarkers to stratify patients who might respond to endothelial-targeted therapies, and funding for trials that move beyond repurposing drugs already shown ineffective in progressive disease.
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 · 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.
Expert Opinion on Investigational Drugs · 2000 · 10 citations
Drugs in development for the treatment of multiple sclerosis: antigen non-specific therapies-an update
AbstractIn the past few years there has been significant progress in the development of therapy for the treatment of relapsing remitting and secondary progressive multiple sclerosis. Research interest in multiple sclerosis (MS) therapeutics has remained high and clinical investigation into potential new therapies continues. This review summarises the advances with currently available therapies and briefly outlines the results from studies with other drugs being developed for the treatment of multiple sclerosis.
Revista de Neurología · 2022 · 0 citations · open access
Plasmaféresis periódica como tratamiento de mantenimiento en la esclerosis múltiple remitente-recurrente, ¿nueva línea terapéutica? A propósito de un caso
AbstractINTRODUCTION: Relapsing-remitting multiple sclerosis (RRMS) treatment has significantly changed in recent years because of the discovery of new molecules that have shown efficacy as maintenance treatment. However, the classical treatment for acute attacks is based on corticosteroids administration, being the periodical plasmapheresis the alternative treatment in the case of refractory patients. We introduce a case of relapsing-remitting multiple sclerosis treated with a classical acute attacks therapy: plasmapheresis. CASE REPORT: The case of a 39-year-old patient who was diagnosed with relapsing-remitting multiple sclerosis, postpartum debut and aggresive course, who, after suboptimal response to disease modifying therapies (alemtuzumab and ocrelizumab), receives combination treatment with outpatient periodic plasmapheresis every 3 weeks as maintenance therapy. Good tolerance and response. Clinical stability with this treatment. She has not required new hospital admissions for acute attacks of multiple sclerosis from February 2020 to March 2021. CONCLUSION: Although more specific studies are needed, this case provides information on a potential new maintenance treatment for patients with relapsing-remitting multiple sclerosis refractory to disease-modifying drug therapies.
Oxford University Press eBooks · 2015 · 0 citations
Treatment of Multiple Sclerosisa
AbstractAbstract Treatment of multiple sclerosis (MS) includes 3 categories: prevention of relapses and disease progression; treatment of individual relapses; and treatment of symptoms and complications. This chapter focuses mainly on prevention of relapses and progression by altering the natural course of MS. The medications used are known as disease-modifying drugs (DMDs). The treatment of individual relapses and symptomatic treatment is also briefly covered.
The Journal of Rehabilitation Research and Development · 2011 · 0 citations
Disease-modifying agents in progressive multiple sclerosis: Management of 100 patients at Louis Stokes Cleveland VAMC, Spinal Cord Injury Division
AbstractMultiple sclerosis (MS) is a chronic disease in which disability progresses over time. Progressive forms of MS have a poor prognosis, are associated with greater levels of disability and, unfortunately, are unresponsive to current treatments. Here, we have reviewed the management of 100 patients with MS. The majority of these patients had progressive disease, Expanded Disability Status Scale scores >6, and extensive medical complications. A significant number of patients in this cohort were also treated with MS disease-modifying agents that lack efficacy in patients with progressive disease. Although these drugs are relatively safe, their use here is significantly costly to the healthcare system, with limited benefit to patients. We suggest that these drugs be discontinued in these patients and resources be directed toward symptomatic treatment, rehabilitation needs, and management of medical complications until drugs with proven efficacy become available.
Journal of Neurology Neurosurgery & Psychiatry · 2002 · 0 citations · open access
Meeting the challenge of progressive multiple sclerosis: By Patrick K Coyle and June Halper (Pp 124, US$19.95). Published by Demos Medical Publishing, New York, 2001. ISBN 1 888799 46 3
AbstractHaving been diagnosed in 1982 I have lived for 19 years with a slowly progressive form of multiple sclerosis. I was therefore glad of the opportuntity to catch up on recent developments in the understanding of the disease and discussion of some of the latest options for treatment. Although the book states in the opening paragraph that it is written for people with this form of …
[Disability Progression in SPMS Despite Therapeutic Intervention: Current Status and Perspectives of Treatment with Disease-Modifying Drugs].
AbstractCurrently, siponimod is the only disease-modifying drugs (DMDs) with proven efficacy and safety in clinical trials for secondary progressive multiple sclerosis (SPMS). However, the efficacy of siponimod in preventing disability progression is insufficient and it has not yet been able to deter disability progression. Therefore, it is considered necessary to use DMDs with a high relapse-preventive effect at a relatively early stage of SPMS, while disease activity remains evident. Bruton's tyrosine kinase inhibitors have the potential to prevent progression of all MS disease types and are expected to be the cornerstone of the next generation of treatment. The results of these clinical trials are awaited.
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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