DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for migraine without aura — 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 moduleMigraine without aura 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 migraine without aura 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
phosphatase and actin regulator 1 (PHACTR1) — PHACTR1 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 16pdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6ZEE · 1.9 Å · ligand 3,6,9,12,15,18-HEXAOXAICOSANE (16P). Experimental structure, not a prediction.
What the evidence adds up to
A 2004 review describes cortical spreading depression as the underlying mechanism of migraine aura. The review states that cortical spreading depression upregulates genes for COX-2, TNF-alpha, IL-1beta, galanin, and metalloproteinases. Activation of metalloproteinases leads to blood-brain barrier leakage, allowing potassium, nitric oxide, and adenosine to reach and sensitise dural perivascular trigeminal afferents. In familial hemiplegic migraine, mutations on chromosome 1q23 produce a haploinsufficiency of the sodium/potassium pump, increasing intracellular calcium. The review notes that the role of the brainstem is still poorly described.
A 2010 paper discusses specific problems in clinical treatment trials for migraine with aura, which differ from those for migraine without aura. The authors make recommendations about subject selection, outcome measures, and optimal treatments in relation to aura and headache, based on their experience with four such trials. No concrete efficacy data, response rates, or survival numbers are reported in this methodological paper.
A 1997 study administered a standardised questionnaire to 45 migraineurs to examine overlap between migraine with and without aura. The results indicate a significant overlap, most importantly with respect to response to therapy: 70% of patients had similar responses. No specific drug or treatment is named in this abstract.
What is still missing are large, well-controlled trials that separate migraine with aura from migraine without aura, given the methodological challenges noted in 2010. The 2004 review identifies target molecules but no tested therapies. Patient stratification by aura status and genetic subtype remains unaddressed in treatment studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2004 · 75 citations
Migraine aura: new information on underlying mechanisms
AbstractPURPOSE OF REVIEW: Since the initial description of cortical spreading depression by Leao, evidence that cortical spreading depression is the underlying pathomechanism of migraine aura has increased. The purpose of this review is to describe the ultimate genetic and molecular mechanisms of migraine aura. RECENT FINDINGS: It has been debated how a primarily cortical phenomenon (aura phase) may activate trigeminal fibres (headache phase). Recent data have demonstrated a link between cortical events and activation of the pain-sensitive structures of the dura mater. The initial cortical hyperperfusion in cortical spreading depression is partly mediated by the release of trigeminal and parasympathetic neurotransmitters from perivascular nerve fibres, whereas delayed meningeal blood flow increase is mediated by a trigeminal-parasympathetic brainstem connection. With regard to molecular mechanisms, cortical spreading depression upregulates a variety of genes coding for COX-2, TNF-alpha and IL-1beta, galanin or metalloproteinases. The activation of metalloproteinases leads to leakage of the blood-brain barrier, allowing potassium, nitric oxide, adenosine and other products released by cortical spreading depression to reach and sensitize the dural perivascular trigeminal afferents. In familial hemiplegic migraine, new mutations have been described in chromosome 1q23, leading to a haploinsufficiency of the sodium/potassium pump, producing an increase in intracellular calcium, similar to the CACNA1A mutation. SUMMARY: Recent studies have helped unravel the basic mechanisms involved in migraine aura. Far from being a simple phenomenon, a sequence of events leads from the cortex to the activation of pain-sensitive structures. The role of the brainstem is still poorly described. The identification of target molecules may provide new therapies.
On the methodology of drug trials in migraine with aura
AbstractINTRODUCTION: Specific problems occur in clinical treatment trials for migraine with aura that differ from those encountered in treatment trials for migraine without aura. DISCUSSION: Based on our experience with four such trials, we point to a number of possible solutions and outline areas for future inquiry. We make recommendations about subject selection; the choice, definition and assessment of outcome measures; optimal treatments in relation to aura and headache; and we provide samples of study report forms used to record occurrence of aura and headache in this population.
Migraine with and Without Aura in the Same Patient
AbstractMigraine with aura and migraine without aura may be different clinical expressions of one disease. This theory is debated, however. In order to further address the issue, we administered a standardized questionnaire to 45 migraineurs. The results indicate a significant overlap between migraine with and without aura, most importantly with respect to response to therapy; 70% of patients had similar responses.
INTERNATIONAL NEUROLOGICAL JOURNAL · 2021 · 1 citations · open access
Migraine: features of pharmacotherapeutic and drug-free preventive treatment
AbstractMigraine is one of the most common forms of headache, which can lead to a significant reduction in quality of life. There is migraine with aura, migraine without aura, as well as chronic migraine, which significantly reduces the efficiency of patients and is often combined with mental disorders and drug-induced headaches. Complications of migraine include migraine status, persistent aura without a heart attack, migraine heart attack (stroke) and epileptic seizure caused by migraine aura. The diagnosis of migraine is established based on complaints, medical history, objective examination data, and diagnostic criteria of the International Headache Classification of the 3rd revision. Additional research methods are recommended only in the presence of “red flags” — symptoms that alert to the secondary nature of the headache. Migraine treatment is aimed at reducing the frequency and intensity of attacks, reducing the number of pharmatherapeutical analgesics. It includes three main approaches: seizure relief therapy, preventive therapy, and non-drug methods. Non-steroidal anti-inflammatory drugs, simple and combined analgesics, triptans, as well as anti-nausea drugs (for severe nausea or vomiting) are recommended for seizures relief. In case of frequent or severe migraine attacks, as well as in case of chronic migraine, prophylactic therapy is indicated, which includes antidepressants, topiramate, beta-blockers, angiotensin II receptor antagonists, botulinum toxin type A-hemagglutinin complex and monoclonal antibodies to calcitonin gene-related peptide receptors. Pharmacotherapy is recommended to be combined with non-drug methods, which include cognitive-behavioral therapy, the method of transcranial magnetic stimulation, the method of biological feedback, postsphygmic period, acupuncture, therapeutic exercises, block of greater occipital nerve, and stimulation of the first trigeminal nerve.
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.
