DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for chronic fatigue syndrome — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChronic fatigue syndrome maps to a 31-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
approvedMethylphenidateApproved drug
Structures already discussed alongside chronic fatigue syndrome in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
spectrin repeat containing nuclear envelope protein 1 (SYNE1) — SYNE1 is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has triethylene glycol bound in it, shown as sticks.
Loading structure…
helix sheet pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6R15 · 1.82 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
A 2004 trial of patient education to encourage graded exercise in 114 patients with chronic fatigue syndrome found that 55% no longer met trial criteria for CFS at two-year follow-up, compared with 56% at one year. In a crossover group of 32 patients who received the intervention after a one-year delay, 47% achieved a good outcome at one year and 23% no longer met CFS criteria. The authors concluded that delaying treatment was associated with reduced efficacy and required more intensive therapy.
A 2021 retrospective review of three patients with treatment-resistant CFS (mean duration 17.66 years) reported that adding modafinil to cognitive-behavioural therapy led to clinically meaningful improvements in energy and pain or concentration in two of three patients, and all three achieved social recovery defined as return to work or full-time training. The sample is three patients, no control group, and the authors describe modafinil as a potentially useful potentiating agent when added to CBT.
A 2016 prospective single-blind trial randomised 71 CFS patients to systematic psychological and behavioural intervention (31 patients) or antidepressant drug treatment alone (40 patients). The psychological and behavioural intervention group showed statistically significant improvements on all four subscales of the Chronic Fatigue Assessment Scale, while the antidepressant-only group showed no significant improvement on any subscale. The total effective rate was significantly higher in the intervention group. The psychological and behavioural intervention group had no dropouts; the antidepressant group had eight dropouts. The authors noted that treatment efficacy was better in patients with a disease course of less than 12 months.
A 2001 twin study of 146 female-female twin pairs found higher concordance rates in monozygotic than dizygotic twins for all definitions of chronic fatigue. For idiopathic chronic fatigue (excluding medical and psychiatric exclusionary criteria), concordance was 55% in monozygotic and 19% in dizygotic twins. Estimated heritability for idiopathic chronic fatigue was 51% (95% CI 7–96). A 2006 commentary notes that patient selection and methods of outcome assessment remain problematic in CFS therapeutic studies, and that these methodological issues may confound pragmatic treatment recommendations. What is still missing are adequately powered, controlled trials with clear patient stratification, standardised outcome measures, and long-term follow-up that account for the heterogeneity of the condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The British Journal of Psychiatry · 2004 · 73 citations · open access
Patient education to encourage graded exercise in chronic fatigue syndrome
AbstractBACKGROUND: An earlier trial demonstrated good outcomes after 1 year for patients with chronic fatigue syndrome (CFS) who received an educational intervention designed to encourage graded activity. AIMS: To determine 2-year outcomes for the same treated patients and the response to treatment of patients formerly in the control condition. METHOD: Patients in the treatment groups (n=114) were followed up at 2 years; 32 patients from the control group were offered the intervention after 1 year and were assessed 1 year later. Assessments were the self-rated measures used in the original trial. RESULTS: At 2 years 63 of the treated patients (55%) no longer fulfilled trial criteria for CFS compared with 64 patients (56%) at 1 year. Fourteen of 30 crossover patients (47%) achieved a good outcome at 1 year and seven (23%) no longer fulfilled criteria for CFS. CONCLUSIONS: Benefits of the intervention were maintained at 2 years. Delaying treatment is associated with reduced efficacy and required more intensive therapy.
AbstractChronic Fatigue Syndrome is a disorder which is characterised by profound fatigue together with a variety of other subjective clinical features which persist over a prolonged period of time. The aetiology remains at present uncertain and therefore rational therapeutic strategies are difficult to plan. This paper reviews currently used forms of treatment aimed at correcting the possible pathophysiological mechanisms and discusses the problems associated with the management of this condition.
BMJ Case Reports · 2021 · 8 citations · open access
Recovery from refractory chronic fatigue syndrome with CBT and modafinil
AbstractMany patients with chronic fatigue syndrome (CFS) fail to derive benefit from evidence-based treatments such as cognitive-behavioural therapy (CBT) and graded exercise therapy leading to permanent disability. To discover whether a repeat prescription of modafinil might potentiate the benefits of CBT leading to social recovery as defined by 2 or more point improvement in energy and muscular pain/concentration and return to work or full-time training. Three patients with treatment-resistant CFS (mean duration 17.66 years) treated with modafinil and CBT in a Liaison Psychiatry clinic were retrospectively reviewed. Progress was reviewed at baseline, 4-6 months and 10-24 months. Patients rated their fatigue, pain and concentration using 10-point Likert scales. 2/3 achieved clinically meaningful improvements in energy and pain/concentration and 3/3 achieved social recovery. Modafinil, when prescribed over the medium term, would appear to be a potentially useful potentiating agent when added to CBT.
Journal of Clinical Oncology · 2024 · 7 citations · open access
Putting Methylphenidate for Cancer-Related Fatigue to Rest?
AbstractIn the article that accompanies this editorial, Stone et al. present a randomized, double-blind, placebo-controlled trial of individually dose-titrated methylphenidate for treatment of fatigue in patients with advanced cancer, finding that methylphenidate, while safe and well-tolerated, was no more effective than placebo at relieving fatigue after 6 (±2) weeks. Future studies should consider the multifaceted nature of cancer-related fatigue, as well as the substantial placebo effects of psychostimulants, and may benefit from focusing on methylphenidate in combination with non-pharmacological interventions, or for fatigue with a predominant emotional or cognitive component.
Clinical methodology and its implications for the study of therapeutic interventions for chronic fatigue syndrome: a commentary
AbstractChronic fatigue syndrome (CFS) is a complex, multisymptom illness of unknown etiology. A variety of operational case definitions based on symptom report have been developed that share some common clinical features. Patients often come to clinical presentation after months or, more typically, years of symptomatic distress. Comorbid presentation with psychiatric illnesses has been noted. Due to these fundamental issues, the impact of patient selection and the specification of the methods of outcome assessment loom large in therapeutic studies of CFS. While a substantial body of research has focused on increasing our understanding of the basic pathobiology of CFS, there have been comparatively fewer studies that have addressed the problems of patient characterization and outcome assessment. The role of clinical methodology in the study of the therapeutics of CFS is not trivial, and may confound our understanding of pragmatic recommendations for treatment.
Effect of psychological and behavioral intervention on the rehabilitation of patients with chronic fatigue syndrome
AbstractObjective
To investigate the psychological and behavioral intervention on the rehabilitation of patients with chronic fatigue syndrome.
Methods
In this prospective, single blind study, 71 outpatients diagnosed with chronic fatigue syndrome according to the criteria of the U. S. Centers for Disease Control were recruited and were divided randomly into two groups by coin method, one group for systematic psychological and behavioral intervention (31 cases) and the other group (the control group) for antidepressant drug treatment only (40 cases). Chronic Fatigue Assessment Scale (FAI) was used to estimate patients' clinical efficacy.
Results
Each factor score of FAI in psychological and behavioral intervention group was significantly improved after treatment (S (3.20±1.72); SS(4.01±1.32); PC(4.95±1.82); RTR / S(6.02±1.59))(P 0.05), Total improvement was not clear (P>0.05). Research group of significant efficiency, the total effective rate was significantly higher than that of control group. Compliance results showed, psychological behavior intervention group follow-up without falling off, the control group had 8 cases to fall off. Psychological and behavior intervention treatment efficacy and disease course, <12 months in patients with good effect.
Conclusion
Both of psychological and behavioral interventions and antidepressant medication are effective therapies for patients with chronic fatigue syndrome, the former is slightly better.
Key words:
Psychological and behavioral intervention; Chronic fatigue syndrome
AbstractOBJECTIVE: The etiology of chronic fatigue syndrome is unknown, but genetic influences may be important in its expression. Our objective was to assess the role of genetic and environmental factors in unexplained chronic fatigue. METHODS: A classic twin study was conducted using 146 female-female twin pairs, of whom at least one member reported > or =6 months of fatigue. After completing questionnaires on symptoms, zygosity, physical health, and a psychiatric interview, twins were classified using three increasingly stringent definitions: 1) chronic fatigue for > or =6 months, 2) chronic fatigue not explained by exclusionary medical conditions, and 3) idiopathic chronic fatigue not explained by medical or psychiatric exclusionary criteria of the chronic fatigue syndrome case definition. Concordance rates in monozygotic and dizygotic twins were calculated for each fatigue definition along with estimates of the relative magnitude of genetic and environmental influences on chronic fatigue. RESULTS: The concordance rate was higher in monozygotic than dizygotic twins for each definition of chronic fatigue. For idiopathic chronic fatigue, the concordance rates were 55% in monozygotic and 19% in dizygotic twins (p =.042). The estimated heritability in liability was 19% (95% confidence interval = 0-56) for chronic fatigue > or =6 months, 30% (95% confidence interval = 0-81) for chronic fatigue not explained by medical conditions, and 51% (95% confidence interval = 7-96) for idiopathic chronic fatigue. CONCLUSIONS: These results provide evidence supporting the familial aggregation of fatigue and suggest that genes may play a role in the etiology of chronic fatigue syndrome.
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.
