DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for advanced sleep phase syndrome — 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 moduleAdvanced sleep phase syndrome 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 advanced sleep phase syndrome 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.
What the evidence adds up to
Chronotherapy, a drug-free rescheduling treatment, was tested in five patients with a 4–15 year history of delayed sleep phase insomnia. All five reported lasting resolution of symptoms, with average sleep onset advancing from 4:50 a.m. to 12:20 a.m. and wake times from 1:00 p.m. to 7:55 a.m., with no reduction in sleep efficiency. All five ended their dependence on hypnotic medications. A later study of 14 adults with delayed sleep phase syndrome found that six patients treated with chronotherapy showed full recovery just after treatment, but in three of them the phase delay relapsed within one year. Four of five patients treated with pharmacotherapy alone showed only partial recovery. Of nine patients followed for more than three years, six had good prognoses but still had a mild phase delay and had to shorten sleep time to work full-time; three had poor prognoses, one requiring psychiatric treatment for affective instability.
Advanced sleep phase syndrome is listed among intrinsic circadian rhythm sleep disorders, alongside delayed sleep phase syndrome, non-24-hour sleep-wake syndrome, and irregular sleep-wake pattern. Treatments discussed include behavioural measures, chronotherapy, bright light treatment, and pharmacological treatments such as melatonin. The paper notes limitations and drawbacks of the various treatments but provides no trial data specific to advanced sleep phase syndrome.
Lemborexant, a dual orexin receptor antagonist, is in phase II/III studies for insomnia, not for advanced sleep phase syndrome. In a phase II proof-of-concept study, six doses from 1 to 25 mg or placebo were given for 15 nights; at all doses lemborexant induced sleep, reduced latency to sleep, and reduced wake after sleep onset. Adverse events were primarily headache and dose-related somnolence. No data exist for lemborexant in advanced sleep phase syndrome.
One abstract discusses sleep deprivation and phase advance of the sleep-wake cycle as antidepressant modalities, noting that shifting sleep earlier can produce improvement within about two days, lasting about two weeks. This is not a treatment for advanced sleep phase syndrome but a chronotherapeutic approach for depression. No controlled trials have established a reliable, long-term treatment for advanced sleep phase syndrome itself. What is missing are adequately powered, randomised trials with objective sleep measures, long-term follow-up, and clear patient stratification by circadian phenotype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
SLEEP · 1981 · 356 citations
Chronotherapy: Resetting the Circadian Clocks of Patients with Delayed Sleep Phase Insomnia
AbstractWe report here the development of a brief drug-free rescheduling treatment ("chronotherapy") for Delayed Sleep Phase (DSP) insomnia, a syndrome characterized by sleep-onset insomnia with difficulty in morning awakening. We postulated that patients with DSP insomnia had an inadequate capacity to achieve phase advance shifts of the circadian pacemaker which times the sleep-wake cycle. Chronotherapy was therefore designed to reset these patients' biological clocks by the phase delay route. This single 5-6 day treatment was tested in 5 patients with a 4-15 year history of DSP insomnia. All 5 patients reported a lasting resolution of their symptoms substantiated by systematic long-term self-reports and objective polygraphic recording before and after treatment (average follow-up of 260 days; range, 42-910 days). The average sleep onset advanced from 4:50 a.m. before treatment to 12:20 a.m. afterwards, and wake times advanced from 1:00 p.m. to 755 a.m. (for both, p less than 0.001), with no reduction in sleep efficiency. As a result, all 5 patients were able to end their chronic dependence on hypnotic medications.
Sleep Medicine Reviews · 1999 · 58 citations · open access
Etiology and treatment of intrinsic circadian rhythm sleep disorders
AbstractSome individuals experience an acute or chronic sleep disturbance, associated with a misalignment between the timing of their sleep and the sleep-wake cycle that is desired, or considered normal by society. It is estimated that 5-10% of insomniacs seeking treatment have this type of disorder, collectively called circadian rhythm sleep disorders. This paper reviews circadian rhythm sleep disorders of the intrinsic type, which include delayed sleep phase syndrome, advanced sleep phase syndrome, non-24-hour sleep-wake syndrome, and irregular sleep-wake pattern. For each disorder, we present data addressing its pathophysiology and potential treatments, including the use of behavioral measures and chronotherapy, bright light treatment and pharmacological treatments such as melatonin. We conclude by addressing some of the limitations and drawbacks of the various treatments.
Psychiatry and Clinical Neurosciences · 1993 · 31 citations
Long‐Term Course of Adult Patients with Delayed Sleep Phase Syndrome
AbstractA response to treatment and long-term course of 14 adults with delayed sleep phase syndrome were investigated with the use of their hospital records and mailed questionnaires. Six patients treated with chronotherapy showed full recovery just after the treatment. In three of them the delay of sleep phase relapsed one year afterwards. Four of five patients treated with pharmacotherapy alone showed partial recovery. Six of nine patients followed for periods of longer than three years after treatment showed good prognoses, though all of them still had a mild phase delay and had to shorten their sleep time in order to work full-time. The three others had poor prognoses and one of them was under psychiatric treatment for affective instability. These findings suggest that a long-term follow-up is needed to judge the effect of the treatment.
Lemborexant. Dual orexin receptor antagonist, Treatment of insomnia
AbstractEisai's lemborexant, or E-2006, is a dual orexin OX1/OX2 receptor antagonist (DORA)in codevelopment withPurdue Pharma. Functionally, lemborexant is about 10-fold selective for OX2 over OX1, whereas it is almost nonselective in recombinant human, rat and mouse receptor binding assays. Lemborexant binds and dissociates rapidly from orexin receptors in contrast to other DORAs, which are typically slow to dissociate. It is relatively stable, shows good bioavailability and brain penetration. In mice, lemborexant enhanced sleep for 4-5 h with effects on both non-REM and REM sleep. Lemborexant is currently in phase II/III clinical studies for the treatment of insomnia. A phase II proof-of-concept study investigated six doses from 1 to 25 mg or placebo administered for 15 nights with polysomnography conducted at baseline and on treatment days 1/2 and 14/15. At all doses, lemborexant induced sleep, reduced latency to sleep and wake after sleep onset. Results of other studies have been reported either in abstract form or as corporate press releases. Lemborexant is apparently well tolerated with moderate adverse events, primarily headache and dose-related somnolence. Some studies are placebo controlled, others against active comparators including flurazepam, zolpidem and/or zopiclone where lemborexant was reported as superior to the latter two drugs, especially with respect to next-morning somnolence, driving performance and balance control. Lemborexant is expected to be submitted to regulatory authorities by 2019 and if registered, market forces will tell whether lemborexant fares better than the first-in-class DORA suvorexant and/or selective OX2 receptor antagonists currently in clinical investigation such as seltorexant (JNJ-54717793/MIN-202) or MK-1064.
S27-01 - Sleep Timing and Sleep Manipulation as Antidepressants
AbstractDisturbed sleep is an intrinsic symptom of depression and may precede or even initiate it. Thus, it is surprising that depriving a patient of sleep can induce improvement, often within hours - however usually with relapse following recovery sleep. Clinical trials of early and late partial sleep deprivation, or shifting sleep earlier, suggest a critical circadian phase where wakefulness is necessary for the antidepressant response. Combination with medication or light therapy can maintain improvement. There is now sufficient evidence for many chronotherapeutic combinations (Table) to support the use of “wake therapy” - the fastest antidepressant modality known - in general psychiatric practice (1). THERAPEUTIC RESPONSE LATENCY DURATION Total (TSD) or partial (PSD) sleep deprivation hours ∼ 1 day Phase advance of the sleep-wake cycle ∼ 2 days ∼ 2 weeks TSD followed by phase advance hours ∼ 2 weeks Repeated TSD or PSD hours days/weeks Repeated TSD or PSD + ADs hours weeks/months Single or repeated TSD or PSD + light therapy; phase advance & light therapy hours weeks/months Single or repeated TSD or PSD + lithium, pindolol, or SSRIs hours months Light therapy (SAD + non-seasonal MD) week(s) weeks/months Light therapy + SSRIs (non-seasonal MD) days months [Circadian and Sleep Therapies of Major Depression]
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.
