DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for conjugate gaze palsy — 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 moduleConjugate gaze palsy 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 conjugate gaze palsy 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
roundabout guidance receptor 3 (ROBO3) — ROBO3 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6POK · 1.796 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In progressive supranuclear palsy, a neurodegenerative tauopathy, disturbance of gaze is a cardinal clinical feature. Studies of 50 patients show that while all forms of eye movements are affected, the predominant defects are in vertical saccades (slow and hypometric, both up and down), impaired vergence, and inability to modulate the linear vestibulo-ocular reflex for viewing distance. These findings, together with early falls, suggest the tauopathy impairs a neural system concerned with bipedal locomotion and frequent gaze shifts. Niemann-Pick Type C, a lysosomal storage disorder, produces a vertical supranuclear saccadic palsy in 95% of patients, with downward saccades deteriorating first; a complete vertical supranuclear gaze palsy with eye movement restriction can develop later.
Three patients with paralysed horizontal gaze showed involuntary convergence substitution, with adduction of both eyes and miosis on attempted gaze into the paralysed field. A 39-year-old male with bilateral horizontal pontine gaze palsy and concurrent esotropia, following neurocysticercosis, underwent classic bimedial rectus recess-resect surgery including resection of the right lateral rectus; three months post-operatively diplopia was markedly improved. In thyroid eye disease, a 50-year-old woman with Graves’ disease presented with binocular vertical diplopia and limited up gaze in the right eye; after 12 days, adduction and down gaze were limited in the left eye with left hypertropia and exotropia. Steroid pulse therapy improved eye movements and strabismus at one month, with no recurrence by nine months.
In young children with dyskinetic cerebral palsy (mean age 4 years 4 months, five children), a six-week home-based trial of two eye-gaze control technology systems found that parents perceived the trial length as appropriate and valued written guidelines. Children showed improvements in goal achievement and performance, but questionnaires on quality of life, participation, and communication outcomes produced substantial missing data, making the measures of limited feasibility. Common lesions causing gaze palsies include cerebral infarcts, demyelinating lesions, multiple sclerosis, tumours, Wernicke’s encephalopathy, metabolic disorders, and neurodegenerative disorders such as progressive supranuclear palsy.
What is still missing are large international studies in children with dyskinetic cerebral palsy to establish whether eye-gaze control technology is effective, longitudinal studies to evaluate surgical approaches for bilateral horizontal gaze palsy with esotropia, and any trial that tests a drug specifically for conjugate gaze palsy as a primary endpoint. Patient stratification by underlying aetiology (tauopathy, lysosomal storage, inflammatory, structural) would be necessary for any such trial, and funding for that work is not described in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Neurology · 2010 · 145 citations · open access
The Disturbance of Gaze in Progressive Supranuclear Palsy: Implications for Pathogenesis
AbstractProgressive supranuclear palsy (PSP) is a disease of later life that is currently regarded as a form of neurodegenerative tauopathy. Disturbance of gaze is a cardinal clinical feature of PSP that often helps clinicians to establish the diagnosis. Since the neurobiology of gaze control is now well understood, it is possible to use eye movements as investigational tools to understand aspects of the pathogenesis of PSP. In this review, we summarize each disorder of gaze control that occurs in PSP, drawing on our studies of 50 patients, and on reports from other laboratories that have measured the disturbances of eye movements. When these gaze disorders are approached by considering each functional class of eye movements and its neurobiological basis, a distinct pattern of eye movement deficits emerges that provides insight into the pathogenesis of PSP. Although some aspects of all forms of eye movements are affected in PSP, the predominant defects concern vertical saccades (slow and hypometric, both up and down), impaired vergence, and inability to modulate the linear vestibulo-ocular reflex appropriately for viewing distance. These vertical and vergence eye movements habitually work in concert to enable visuomotor skills that are important during locomotion with the hands free. Taken with the prominent early feature of falls, these findings suggest that PSP tauopathy impairs a recently evolved neural system concerned with bipedal locomotion in an erect posture and frequent gaze shifts between the distant environment and proximate hands. This approach provides a conceptual framework that can be used to address the nosological challenge posed by overlapping clinical and neuropathological features of neurodegenerative tauopathies.
Developmental Neurorehabilitation · 2018 · 25 citations · open access
Eyes on communication: trialling eye-gaze control technology in young children with dyskinetic cerebral palsy
AbstractPURPOSE: This study aims to identify eye-gaze control technology outcomes, parent perception of the technology and support received, and gauge the feasibility of available measures. METHODS: Five children with dyskinetic cerebral palsy, mean age 4 years, 4 months (1 year, 0 months); n = 4 males; trialled two eye-gaze control technology systems, each for six weeks. Parents completed pre- and post-questionnaires. RESULTS: Parents found the 6-week home-based trial period to be the right length. Written guidelines and instructions about set-up, calibration, and play and learning activities were perceived as important. Children demonstrated improvements in goal achievement and performance. Parents found questionnaires on quality of life, participation, behaviours involved in mastering a skill and communication outcomes challenging to complete resulting in substantial missing data. CONCLUSION: Eye-gaze control technology warrants further investigation for young children with dyskinetic cerebral palsy in a large international study.
British Journal of Ophthalmology · 1995 · 15 citations · open access
Convergence substitution for paralysed horizontal gaze.
AbstractThree patients with paralysed horizontal gaze are presented. Involuntary use of convergence to assist horizontal gaze was noted as a late feature. All patients showed (1) unilateral or bilateral horizontal gaze palsy (two patients had one and a half syndrome, the other had bilateral nuclear sixth nerve palsies), (2) adduction of both eyes on attempted gaze into the paralysed field, (3) miosis which coincided with adduction. Convergence substitution should be considered in the differential diagnosis of gaze induced strabismus.
AbstractA single clear binocular vision is made possible by the nature through the oculomotor system along with inputs from the cortical areas as well their descending pathways to the brainstem. Six systems of supranuclear control mechanisms play a crucial role in this regard. These are the saccadic system, the smooth pursuit system, the vestibular system, the optokinetic system, the fixation system, and the vergence system. In gaze disorders, lesions at different levels of the brain spare some of the eye movement systems while affecting others. The resulting pattern of eye movements helps clinicians to localize lesions accurately in the central nervous system. Common lesions causing gaze palsies include cerebral infarcts, demyelinating lesions, multiple sclerosis, tumors, Wernicke's encephalopathy, metabolic disorders, and neurodegenerative disorders such as progressive supranuclear palsy. Evaluation of the different gaze disorders is a bane of most budding neurologists and neurosurgeons. However, a simple and systematic clinical approach to this problem can make their early diagnosis rather easy.
American Journal of Ophthalmology Case Reports · 2023 · 0 citations · open access
A case of bilateral horizontal gaze palsy and concurrent esotropia
AbstractPurpose: To report a unique case of bilateral horizontal pontine gaze palsy with concurrent esotropia, surgical management, and post-operative follow-up. Observations: A 39-year-old male presented with diplopia and a history of neurocysticercosis. He was found to have bilateral horizontal gaze palsy and concurrent esotropia, R > L. Classic bimedial rectus recess-resect surgery was done to include resection of the right lateral rectus muscle. Follow-up three months post-op demonstrates markedly improved diplopia. Conclusion and importance: We present a recommended therapeutic approach for the rare case of concurrent bilateral horizontal gaze palsy and esotropia, which should be further evaluated in longitudinal studies.
Niemann-Pick Type C: Typical Ocular Motor Findings and Red Flags
AbstractNiemann-Pick Type C (NPC) is a rare, autosomal-recessive lysosomal storage disorder. 95% of all patients develop a vertical supranuclear saccadic palsy (VSSP). First, downward saccades deteriorate. The underlying mechanism is probably a unilateral innervation of the eye depressors by the neurons of the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF) in the mesencephalon. In contrast, the eye elevators are bilaterally innervated by the riMLF and thus they are not functionally impaired until a later stage. During the course of the disease, a complete vertical supranuclear gaze palsy (VSGP) with an eye movement restriction can develop. This is caused by an additional functional impairment of the interstitial nucleus of Cajal.
Annals of Optometry and Contact Lens · 2023 · 0 citations · open access
A Case of Third Cranial Nerve Palsy Accompanying Thyroid Eye Disease
AbstractPurpose: To report a patient who developed thyroid eye disease and third cranial nerve palsy at the same time and showed good response to high dose steroid therapy.Case summary: A 50-year-old woman who was diagnosed with Graves' disease presented with binocular vertical diplopia for 1 month. Diplopia was persistent and did not show any fluctuation daily. Up gaze was limited in the right eye. Orbital computed tomography showed hypertrophy of the inferior rectus muscles in both eyes. After 12 days, she complained of rapid progression of diplopia. Adduction and down gaze were limited in the left eye, and left hypertropia and exotropia were presented. Steroid pulse therapy was administered, and eye movements and strabismus improved at one month after treatment, and there were no recurrences until 9 months after symptom onset.Conclusions: Thyroid eye disease was accompanied by third cranial nerve palsy. If ocular movement is not consistent with the extraocular muscle involved or the forced duction test result in thyroid eye disease, the possibility of combined cranial nerve palsy should be considered.
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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