DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital myasthenic syndrome — screening already-approved drugs against its 37-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital myasthenic syndrome maps to a 37-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 congenital myasthenic 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.
Molecular view
cholinergic receptor nicotinic epsilon subunit (CHRNE) — CHRNE 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 clrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9DMS · 1.92 Å · ligand CHOLESTEROL (CLR). Experimental structure, not a prediction.
What the evidence adds up to
Congenital myasthenic syndrome is a group of rare genetic disorders of neuromuscular transmission. Exact prevalence is unknown; approximately 2000 to 3000 patients worldwide have been diagnosed at the molecular level. Mutations in 14 different genes were known by 2012, and by 2022 more than thirty pathogenic genes had been discovered. The known mutations are estimated to cause roughly 50% of all clinically diagnosed cases. Misdiagnosis and missed diagnosis are common because symptoms can be unspecific and phenotypes vary widely.
Most patients are eligible for drug therapy with esterase inhibitors, 3,4-diaminopyridine, ephedrine, fluoxetine or quinidine, but the effect differs depending on the underlying genetic defect. A 2024 study from one hospital in Algiers reported six patients with different mutations and pathophysiologic profiles who were treated with innovative drugs normally indicated for non-neurological conditions. The authors state the outcome was toward clear clinical improvement, but this study provides only Class IV evidence. A 2013 report of two siblings with familial limb girdle myasthenia showed significant objective clinical improvement after initiation of terbutaline, a potential treatment option in certain subtypes refractory to conventional medicines.
Very little is known about the best treatment and care over a longer period of time. Long-term follow-up is required to determine the overall efficacy and safety profile of terbutaline and other innovative drugs. What is still missing are large, controlled trials with long follow-up, systematic genotype-stratified treatment protocols, and reliable prevalence data that would allow proper trial design and patient stratification.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neuropediatrics · 2012 · 35 citations
Congenital Myasthenic Syndromes: Current Diagnostic and Therapeutic Approaches
AbstractCongenital myasthenic syndromes (CMS) are rare genetically and clinically heterogeneous disorders characterized by an impaired neuromuscular transmission. Exact prevalence data are not available, approximately 2000 to 3000 patients worldwide have been diagnosed on a molecular level; mutations in 14 different genes are known to date leading to causal defects in presynaptic nerve terminal, synaptic cleft, and postsynaptic apparatus. At last, all known mutations are estimated to cause approximately 50% of all clinically diagnosed CMS. However, phenotypes may vary widely and symptoms can be unspecific, therefore CMS are often missed and their prevalence may be underestimated. But, the exact diagnosis is extremely important to start early appropriate therapy to prevent life-threatening events and to improve the clinical course. Most patients are eligible for drug therapy with esterase inhibitors, 3, 4-diaminopyridine, ephedrine, fluoxetine or quinidine, but the effect of these drugs differs depending on the underlying genetic defect. Moreover, very little is known about the best treatment and care in these patients over a longer period of time.This article provides an overview of specific clinical symptoms, diagnostic work-up, and care including possible pharmacotherapy in case of CMS.
AbstractA female infant with neonatal myasthenia gravis remained weak for an excessively long period compared to the usual situation in this disease process. At 71 days of age, electrophysiological studies revealed evidence of a defect in neuromuscular transmission that improved with intravenous Tensilon therapy. Repeat study at 183 days of age was normal. This case represents an unusually long time for an affected infant to have neonatal myasthenia gravis. Electrophysiological studies are of value in the diagnosis and management of patients with neonatal myasthenia gravis.
Neurology Clinical Practice · 2024 · 0 citations · open access
Innovative Therapeutic Approaches in Congenital Myasthenic Syndromes
AbstractBackground and Objectives: To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs. Methods: Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study). Results: Six patients carrying different mutations in different genes of CMSs were studied. They had different pathophysiologic profiles (slow or fast channel syndromes, low expressor of receptor). Their therapeutic management was based on innovative drugs, normally indicated in other, non-neurological pathologies. Their outcome was toward a clear clinical improvement. Discussion: This work relates the interest of proposing treatments (outside of Pyridostigmine) in the management of CMSs. These therapies can greatly modify the prognosis of patients suffering from this orphan disease. Classification of Evidence: This study provides Class IV evidence that for patients with congenital myasthenic syndromes, some innovative treatments are effective.
Annals of Indian Academy of Neurology · 2013 · 0 citations · open access
Efficacy of terbutaline in familial limb girdle myasthenia
AbstractCongenital myasthenic syndromes (CMS) are frequently misdiagnosed due to their wide clinical heterogeneity. Molecular defects in various end-plate associated proteins are being identified. Better understanding of the molecular pathogenesis and genotype-phenotype correlations can help evolve newer therapeutic targets. We present a report of two siblings with familial limb girdle myasthenia who showed significant objective clinical improvement after initiation of terbutaline. The possible mechanism of action and utility of terbutaline in the setting of CMS are described. Terbutaline is a potential treatment option in certain subtypes of CMS refractory to conventional medicines. However, long-term follow-up is required to determine the overall efficacy and safety profile.
Sage Journals Data · 2023 · 0 citations · open access
sj-docx-1-tan-10.1177_17562864231213240 – Supplemental material for Guideline for the management of myasthenic syndromes
AbstractSupplemental material, sj-docx-1-tan-10.1177_17562864231213240 for Guideline for the management of myasthenic syndromes by Heinz Wiendl, Angela Abicht, Andrew Chan, Adela Della Marina, Tim Hagenacker, Khosro Hekmat, Sarah Hoffmann, Hans-Stefan Hoffmann, Sebastian Jander, Christian Keller, Alexander Marx, Arthur Melms, Nico Melzer, Wolfgang Müller-Felber, Marc Pawlitzki, Jens-Carsten Rückert, Christiane Schneider-Gold, Benedikt Schoser, Bettina Schreiner, Michael Schroeter, Bettina Schubert, Jörn-Peter Sieb, Fritz Zimprich and Andreas Meisel in Therapeutic Advances in Neurological Disorders
Myasthenia gravis in an 22 months-old girl - impressing improvement due to early adaequate therapy
AbstractAims: Infantile Myasthenia gravis (MG) is a rare autoimmune disease, antibodies against the nicotinic acetylcholine receptor (AChR) can be found in 50% off all cases. Others as antibodies to muscle-specific kinase (MuSK) are less frequent. The prevalence of MG in infants below 1 year of age is approximately 1.1/106. If antibodies are missing, a congenital myasthenic syndrome (CMS) has to be taken into account. Therapeutical options are the treatment with acetylcholinesterase inhibitors and often also immunosuppression. Depending on clinical severity a plasmapheresis or intravenous immunoglobulin could be indicated. A thymectomy could increase the probability of remission.
DOAJ (DOAJ: Directory of Open Access Journals) · 2022 · 0 citations
Congenital Myasthenic Syndrome
AbstractCongenital Myasthenic syndrome (CMS) is a group of partially treatable genetic disorders characterized by dysfunction of neuromuscular junction signaling.With the popularization of high-throughput sequencing and in-depth understanding of the disease in recent years, more than thirty pathogenic genes have been discovered and there is a correlation between genotype and clinical phenotype.Misdiagnosis and missed diagnosis are common in clinical practice. This paper summarized the molecular mechanisms, clinical features, electrophysiologic, pathological features and treatment of main subtypes of CMS to deepen the understanding of the disease.
Scholars International Journal of Obstetrics and Gynecology · 2020 · 0 citations · open access
Myasthenia and Pregnancy: About one Case
AbstractMyasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction affecting mainly young women, on this poster reporting a clinical case of a parturient parturient of 21 years old, primiparous, diagnosed myasthenia for 6 years, thymectomized, under corticosteroid therapy, azathioprine and mytelase, who presents for a pregnancy of 36 SA + 3 without signs of muscle weakness. The delivery was carried out vaginally under epidural analgesic giving birth to a newborn of 2kg800, male, Apgar a 4/4/4, lethargic with congenital myasthenia who died after 10 hours of life. The diaper suites were simple at day 4 of the postpartum the parturient presented a serious myasthenic crisis at the paraclinical exploration the biological assessment showed a slight inflammatory syndrome the therapeutic approach consisted in a conditioning of the patient, corticosteroid, prostigmine, azathioprine, mytelase, as well as a cure of 5 days of immunoglobulin. The evolution was favorable at the end of the 3rd day and the patient was transferred to the neurology department on the 6th day and left home at the end of the 10th day.
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.
