DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for relapsing-remitting multiple sclerosis — screening already-approved drugs against its 41-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRelapsing-remitting multiple sclerosis maps to a 41-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 relapsing-remitting 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
For relapsing-remitting multiple sclerosis, treatment decisions are primarily driven by efficacy against relapses, with patients highly engaged in joint decision-making with physicians, especially at first line, according to a 2018 chart-review study covering the 5EU and USA. Convenience factors beyond oral administration were uncommon. The same study noted that patient involvement decreases at later lines of treatment.
A 2015 cohort study from Saskatchewan followed 262 patients with clinically definite relapsing-remitting multiple sclerosis and disability level DSS ≤5.5, enrolled between 1997 and 1999. At 15 years, only 38 of 262 patients (14.5%) remained on their initial prescription: 15 of 131 (11.5%) on Betaseron, 16 of 102 (15.5%) on Copaxone, 7 of 28 (25%) on Rebif, and 0 of 1 on Avonex. A total of 223 patients (63.6%) had discontinued their first drug at a mean duration of 5.5 years. After switching, 95 of 262 (36.4%) remained on some drug. The authors concluded that because of low adherence, the impact of disease-modifying drugs on disease progression in the longer term cannot be verified.
A 2012 review described the then-available disease-modifying drugs for relapsing-remitting multiple sclerosis, noting that injectable interferon beta-1a, interferon beta-1b, and glatiramer acetate had been proven safe as first-line treatments. More potent but potentially more hazardous drugs such as natalizumab, fingolimod, and cladribine were restricted to patients with very active disease or those refractory to first-line treatment. The review also mentioned phase II/III studies showing beneficial effects of teriflunomide, laquinimod, BG-12, rituximab, and alemtuzumab. A 2023 personal viewpoint acknowledged that 30 years after the first disease-modifying therapy was approved, there remains a widening gap between successes in relapsing disease and the unmet need of progressive multiple sclerosis, with no cure and fundamental aspects of the disease still debated.
What is still missing is a clear demonstration that disease-modifying drugs alter long-term disability progression in relapsing-remitting multiple sclerosis, given the low adherence observed in long-term follow-up. The field also lacks effective treatments for progressive disease and repair of nervous system damage. No trial design or patient stratification strategy has yet resolved the disconnect between short-term relapse reduction and long-term disability outcomes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
BMJ Case Reports · 2013 · 29 citations · open access
High dose thiamine improves fatigue in multiple sclerosis
AbstractThe majority of the patients with multiple sclerosis (MS) experience fatigue. Some observations indicate that fatigue and related manifestations concomitant with MS could be associated with an intracellular mild thiamine deficiency. We recruited 15 patients with MS who also experience fatigue and assessed the severity of the fatigue using the Fatigue Severity Scale. Although blood thiamine and thiamine pyrophosphate levels were within normal limit in all the patients, high-dose thiamine therapy administered orally or parenterally led to an appreciable improvement of the fatigue. The absence of apparent decrease in blood thiamine despite the presence of symptoms referable to a mild thiamine deficiency suggests that these patients may have a dysfunction of the mechanisms of intracellular transport or structural enzymatic abnormalities. The administration of large quantities of thiamine was effective in reversing the fatigue in MS, suggesting that the abnormalities in thiamine-dependent processes could be overcome by diffusion-mediated transport at supranormal thiamine concentrations.
Neuropsychiatric Disease and Treatment · 2013 · 18 citations · open access
Role of oral teriflunomide in the management of multiple sclerosis
AbstractThe landscape of the treatment of relapsing-remitting multiple sclerosis is changing fast. Several oral treatments have shown benefit and generate much interest because of the convenience of their administration. Two oral compounds, fingolimod and teriflunomide, have been approved in relapsing-remitting multiple sclerosis, while others have completed Phase III trials and are awaiting review for registration. Teriflunomide is a pyrimidine synthesis inhibitor with selective immunomodulatory and immunosuppressive properties that have shown consistent efficacy in clinical trials, and a good safety profile. This paper provides an overview of the mechanisms of action and efficacy and safety results from clinical trials with this drug. The role of teriflunomide in the treatment of relapsing-remitting multiple sclerosis is discussed.
Physician and Patient Treatment Decision-Making in Relapsing-Remitting Multiple Sclerosis in Europe and the USA
AbstractOBJECTIVE: To assess factors used in treatment decision-making for relapsing-remitting multiple sclerosis in both the 5EU (UK/Germany/France/Italy/Spain) and the USA. METHODS: Data were abstracted from the Ipsos Healthcare Global Multiple Sclerosis Therapy Monitor (data abstracted September-December, 2015-2017) a bi-annual online chart-review study of patients with multiple sclerosis. RESULTS: Treatment choices were primarily due to efficacy for relapses while convenience factors, other than oral administration, were uncommon. Predominantly, the choice of disease modifying therapy at first line was jointly made, with patient involvement decreasing at later lines of treatment. CONCLUSION: Relapsing-remitting multiple sclerosis patients are highly engaged in their treatment decisions, particularly early in the pathway. The majority were made jointly between the physician and patient, driven by efficacy.
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.
Expert Review of Clinical Immunology · 2014 · 6 citations · open access
Teriflunomide for the treatment of relapsing–remitting multiple sclerosis
AbstractTeriflunomide, a once-daily, oral disease-modifying therapy, is a valuable new treatment option for the management of patients with relapsing-remitting multiple sclerosis. This article reviews key efficacy and safety data arising from pivotal teriflunomide studies that demonstrate the utility in treating both treatment-naïve patients and those previously treated with another disease-modifying therapy who, for a variety of reasons, may require an alternative treatment.
Abstract30 years ago the first disease-modifying therapy for relapsing multiple sclerosis was approved for use in the United States and soon thereafter across the globe. Since then the field of MS therapeutics, and studies of immunopathogenesis and genetics, have advanced our understanding of the disease and raised the hope of better addressing the next challenges of treating progressive disease, enhancing repair of the damaged nervous system and, hopefully, of a cure. Thirty years into the MS treatment era, the field continues to debate fundamental aspects of MS, and there exists a widening chasm between the triumphs in relapsing disease and the desolation of MS progression, which remains the principal unmet need. In this Personal Viewpoint, we outline lessons learned from the first era of great therapeutic development, as we look to the future of MS research and therapeutics.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · 2015 · 0 citations · open access
The low adherence and disability outcomes of disease-modifying drugs in Multiple Sclerosis in Saskatchewan, a cohort study, 1997-2014
AbstractBackground: The beneficial effects of the injected disease-modifying drugs (DMDs) in relapsing-remitting Multiple Sclerosis have been previously reported. However the results related to disability outcomes and the reduction of disease progression in the pivotal trials and few longer studies are variable and inconclusive. Objectives: To determine the utilization and the disability outcomes of the DMDs on relapsing-remitting Multiple Sclerosis over fifteen years. Methods: A prospective open-label cohort of 262 clinical definite patients, 78 men and 184 women, with two attacks in the past two years and a disability level DSS≤5.5 were enrolled consecutively from December 1997 to November 1999. A descriptive analysis of the cohort and individual drugs outcomes were performed. The results were compared to natural history studies of Multiple Sclerosis as controls. Results: At 15 years, one-seventh, 38/262 (14.5%) remain on the initial prescription, Betaseron, 15/131 (11.5%), Copaxone, 16/102 (15.5%) and Rebif 7/28 (25%), Avonex 0/1. 223(63.6%) had discontinued at a mean duration of 5.5(SD=4.7) years. 95/262 (36.4%) remain on a drug after switches. The DSS levels of the individual DMDs were analyzed. Conclusion: One-seventh of participants remained on their first prescription. Because of low adherence, the impact of DMDs on disease progression in the longer term cannot be verified.
E-Health 2.0 Developments in Treatment and Research in Multiple Sclerosis
AbstractThe treatment of multiple sclerosis (MS) is entering a new era, characterized by the availability of a broad range of disease modifying drugs (DMDs) for patients in the relapsing-remitting (RR) phase of the disease. Through interference with immunemediated inflammatory processes the DMDs reduce the number and severity of relapses and the increase in relapse-related disability. Each DMD is characterized by a unique combination of mode of action, route of administration, degree of efficacy and potential side effects. In the past two decades the injectable drugs interferon beta-1a (INFb-1a), INFb-1b and glatiramer acetate (GA) have been proven to be safe first-line treatments. In more recent years, the intravenously administered monoclonal antibody natalizumab and the oral drugs fingolimod and cladribine have been demonstrated to be efficacious in RRMS. These DMDs are more potent, but also potentially more hazardous, which by and large restricts their use to patients who have very active disease or are refractory to firstline treatment. Lately, phase II/III studies showed beneficial effects of the oral drugs teriflunomide, laquinimod and BG-12, and the monoclonal antibodies rituximab and alemtuzumab in RRMS. The advent of the new treatments coincides with the Web 2.0 evolution of the internet technology. Web 2.0 offers patients, doctors, and nurses unforeseen possibilities to fundamentally change, and hopefully improve, the ways in which care is delivered and clinical, patient-centered research is performed. The term Web 2.0 is associated with web applications that facilitate participatory information sharing, inter-operability, user-centered design and collaboration on the World Wide Web [1]. A Web 2.0 site allows users to interact and collaborate with each other, e.g. as creators of user-generated content in a virtual community, in contrast to websites where users are limited to the passive viewing of content that was created for them [2].
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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