DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for migraine with aura — screening already-approved drugs against its 25-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleMigraine with aura maps to a 25-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 with 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
mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) — MAP4K4 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 3-chlorophenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4OBO · 2.1 Å · ligand 6-(3-chlorophenyl)quinazolin-4-amine (2QV). Experimental structure, not a prediction.
What the evidence adds up to
A 1997 questionnaire study of 45 migraineurs found that 70% of patients who experienced both migraine with aura and migraine without aura had similar responses to therapy across the two presentations, suggesting a clinical overlap. A 2010 methodology paper, drawing on experience from four treatment trials specific to migraine with aura, noted that such trials face distinct problems compared to trials for migraine without aura, and offered recommendations on subject selection, outcome measures, and the timing of treatment relative to aura and headache.
A 2008 review of animal models acknowledged that while these models have led to the identification of drug targets and helped clarify mechanisms for abortive and prophylactic drugs, they have significant shortcomings. The review noted that first-generation models focused on pain-generating intracranial tissues, while later models incorporated cortical spreading depression and mouse mutants expressing human migraine mutations to study familial hemiplegic migraine.
A 2024 proteome-wide Mendelian randomization study identified several plasma proteins as potential drug targets for migraine and its subtypes, including migraine with aura. The analysis integrated plasma protein quantitative trait loci with genome-wide association study findings. The study reported that the identified targets—FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3—showed no major disease side effects in a phenome-wide assessment and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of these plasma proteins on migraine were partly mediated by plasma metabolites, with mediation proportions ranging from 3.8% to 21.0%. The study did not report any clinical trial results, survival data, or response rates. What remains missing is prospective clinical validation of these protein targets in migraine with aura patients, along with dedicated trial designs that account for the specific methodological challenges of aura trials, and adequate funding to move from genetic association to interventional 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 · 2008 · 48 citations
Animal models of migraine headache and aura
AbstractPURPOSE OF REVIEW: Over the past 30 years, animal models of migraine have led to the identification of novel drug targets and drug treatments as well as helped to clarify a mechanism for abortive and prophylactic drugs. Animal models have also provided translational knowledge and a framework to think about the impact of hormones, genes, and environmental factors on migraine pathophysiology. Although most acknowledge that these animal models have significant shortcomings, promising new drugs are now being developed and brought to the clinic using these preclinical models. Hence, it is timely to provide a short overview examining the ways in which animal models inform us about underlying migraine mechanisms. RECENT FINDINGS: First generation migraine models mainly focused on events within pain-generating intracranial tissues, for example, the dura mater and large vessels, as well as their downstream consequences within brain. Upstream events such as cortical spreading depression have also been modeled recently and provide insight into mechanisms of migraine prophylaxis. Mouse mutants expressing human migraine mutations have been genetically engineered to provide an understanding of familial hemiplegic migraine and possibly, by extrapolation, may reflect on the pathophysiology of more common migraine subtypes. SUMMARY: Animal models of migraine reflect distinct facets of this clinically heterogeneous disorder and contribute to a better understanding of its pathophysiology and pharmacology.
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.
The Journal of Headache and Pain · 2024 · 12 citations · open access
Proteome-wide Mendelian randomization identified potential drug targets for migraine
AbstractBACKGROUND: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). METHODS: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. RESULTS: ), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). CONCLUSIONS: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.
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.
Research Journal of Pharmacy and Technology · 2020 · 2 citations
A Prospective Study of Propranolol and Flunarizine in the Prophylactic Therapy of Migraine in a Tertiary Care Hospital
AbstractMigraine is a common, recurrent, severe headache that interferes with normal functioning and quality of life (QOL). This prospective observational study was conducted to evaluate and compare the effectiveness and safety flunarizine(10mg), calcium channel antagonist, and propranolol(40mg) in the prophylaxis of migraine with or without aura. This Study included 70 patients of migraine and was divided into 2 treatment groups. SF 36 v1 questionaire were used for the evaluation of health related QOL. Both treatment groups led to a significant reduction in severity, frequency and duration after one month. The difference between two treatments was statistically significant. Sedation was noted with both treatments. Propranolol can be the better treatment for reducing the severity and frequency of migraine.
Pain Research and Management · 2025 · 2 citations · open access
Treatment of Migraine With Phytocannabinoids, the Involvement of Endocannabinoids in Migraine, and Potential Mechanisms of Action
AbstractThe American Migraine Foundation estimates that over 39 million Americans and over 1 billion people worldwide suffer from some form of migraine. Treatment of migraine generally falls into two categories: treatment of attacks once they have begun, and prophylactic prevention, including lifestyle changes. The use of phytocannabinoids to reduce both the frequency and severity of migraine is widely documented in scientific, grey, and popular literature. This review provides descriptions of both preclinical and clinical studies involving the treatment of migraines with phytocannabinoids as well as the involvement of endocannabinoids and endocannabinoid-like compounds in migraine pathology, including the receptors and associated mechanisms. Currently unanswered questions and areas for further exploration are discussed.
Journal of Family Planning and Reproductive Health Care · 2016 · 0 citations · open access
A very specific absence of focus? A patient's response to ‘Diagnosing migraine’
AbstractAs a sufferer from ‘classic’ migraine with aura from the age of 15 years, who has in the past used a combined oral contraceptive pill during my 30s, I read Anne MacGregor's review article1 with great interest. Safe prescription of contraception for those of us who suffer from migraine has to be important, and this article promised clarification and assistance. In my case, my general practitioner didn't include aura symptoms as any determinant of medication, although, to …
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.
