DeCure for Paramyotonia congenita of Von Eulenburg
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for paramyotonia congenita of Von Eulenburg — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleParamyotonia congenita of Von Eulenburg maps to a 6-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 paramyotonia congenita of von eulenburg 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
carbonic anhydrase 2 (CA2) — CA2 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 hydroxymercurydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3K34 · 0.9 Å · ligand 4-(HYDROXYMERCURY)BENZOIC ACID (HGB). Experimental structure, not a prediction.
What the evidence adds up to
In a double-blind randomised crossover trial of 26 patients with genetically confirmed non-dystrophic myotonias (including paramyotonia congenita), lamotrigine reduced the Myotonic Behaviour Scale score by 1.3 ± 0.2 points (P < 0.001) compared with 0.2 ± 0.1 for placebo (P = 0.4). The estimated effect size was 1.0 ± 0.2 (95% CI 0.5–1.5, P < 0.001, n = 22). The number needed to treat was 2.6 (P = 0.006, n = 26). One patient withdrew due to an allergic reaction to lamotrigine; the number needed to harm was 5.2 (P = 0.11, n = 26). The authors concluded lamotrigine should be used as first-line treatment for myotonia in treatment-naive patients with non-dystrophic myotonias, citing its low cost and availability.
A 2007 report tested propafenone hydrochloride in a single 42-year-old man with paramyotonia congenita from a large affected family. He had previously taken mexiletine 200 mg three times daily, which reduced muscle stiffness but caused nausea, vomiting, constipation, and confusion requiring discontinuation. The paper describes propafenone as chosen on theoretical grounds for its pharmacologic properties, but provides no quantitative results for its efficacy in this patient.
A 2009 family study followed members with paramyotonia congenita over 19 years. It notes that at later age, increased stiffening of desmogenic nature occurred in wrist and finger joints. Four family members developed paralysis agitans. One autopsy showed no central nervous system changes beyond normal age-induced alterations, and muscle fibre changes without clear preferred localisation. Atrophy of the ciliary body was found in the eye.
What remains missing is a larger randomised trial of propafenone in paramyotonia congenita, any head-to-head comparison of lamotrigine with mexiletine in this specific condition, and patient stratification by SCN4A mutation type. The long-term natural history data come from a single family and one autopsy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Brain · 2017 · 71 citations · open access
The antimyotonic effect of lamotrigine in non-dystrophic myotonias: a double-blind randomized study
AbstractMexiletine is the only drug with proven effect for treatment of non-dystrophic myotonia, but mexiletine is expensive, has limited availability and several side effects. There is therefore a need to identify other pharmacological compounds that can alleviate myotonia in non-dystrophic myotonias. Like mexiletine, lamotrigine is a sodium channel blocker, but unlike mexiletine, lamotrigine is available, inexpensive, and well tolerated. We investigated the potential of using lamotrigine for treatment of myotonia in patients with non-dystrophic myotonias. In this, randomized double-blind, placebo-controlled, two-period cross-over study, we included adult outpatients recruited from all of Denmark with clinical myotonia and genetically confirmed myotonia congenita and paramyotonia congenita for investigation at the Copenhagen Neuromuscular Center. A pharmacy produced the medication and placebo, and randomized patients in blocks of 10. Participants and investigators were all blinded to treatment until the end of the trial. In two 8-week periods, oral lamotrigine or placebo capsules were provided once daily, with increasing doses (from 25 mg, 50 mg, 150 mg to 300 mg) every second week. The primary outcome was a severity score of myotonia, the Myotonic Behaviour Scale ranging from asymptomatic (score 1) to invalidating myotonia (score 6), reported by the participants during Weeks 0 and 8 in each treatment period. Clinical myotonia was also measured and side effects were monitored. The study was registered at ClinicalTrials.gov (NCT02159963) and EudraCT (2013-003309-24). We included 26 patients (10 females, 16 males, age: 19-74 years) from 13 November 2013 to 6 July 2015. Twenty-two completed the entire study. One patient withdrew due to an allergic reaction to lamotrigine. Three patients withdrew for reasons not related to the trial intervention. The Myotonic Behaviour Scale at baseline was 3.2 ± 1.1, which changed after treatment with lamotrigine by 1.3 ± 0.2 scores (P < 0.001), but not with placebo (0.2 ± 0.1 scores, P = 0.4). The estimated effect size was 1.0 ± 0.2 (95% confidence interval = 0.5-1.5, P < 0.001, n = 22). The standardized effect size of lamotrigine was 1.5 (confidence interval: 1.2-1.8). Number needed to treat was 2.6 (P = 0.006, n = 26). No adverse or unsuspected event occurred. Common side effects occurred in both treatment groups; number needed to harm was 5.2 (P = 0.11, n = 26). Lamotrigine effectively reduced myotonia, emphasized by consistency between effects on patient-related outcomes and objective outcomes. The frequency of side effects was acceptable. Considering this and the high availability and low cost of the drug, we suggest that lamotrigine should be used as the first line of treatment for myotonia in treatment-naive patients with non-dystrophic myotonias.
AbstractParamyotonia congenita (PC) is an autosomal dominant condition with high penetrance linked to SCN4A .1 It is characterized by myotonic stiffness that paradoxically worsens with repeated contractions and with exposure to cold and by episodes of spontaneous or cold-induced paralysis. Pharmacologic treatment of PC is directed toward reducing myotonia and preventing episodes of weakness.2
We tested the clinical and electrophysiologic responses of both myotonia and paralysis to propafenone hydrochloride (PH). PH was chosen as a single-drug treatment for both symptoms on theoretical grounds of its pharmacologic properties.3,4
We studied a 42-year-old man belonging to a large family with several affected members including his two sons. Since early childhood, he had been experiencing muscle stiffness and disabling episodes of paralysis. He had received mexiletine, 200 mg three times daily. A reduction in muscle stiffness was observed, but the appearance of nausea, vomiting, constipation, and confusion required discontinuation of the drug. Therefore, we decided to …
A FAMILY WITH PARAMYOTONIA CONGENITA WITH THE REPORT OF AN AUTOPSY
AbstractA family having paramyotonia congenita was observed through following up a few members over a period of 19 years. The natural history of the syndrome is outlined. This bears out the character of the disease as an entity fully independent of other myotonic conditions. At later age, an increased stiffening of desmogenic nature occurs in the wrist and finger joints. Four members got paralysis agitans. The significance of this feature is discussed. One family member came to post-mortem. In the central nervous system, none but the normal age-induced alterations were observed. A discussion is given of the changes in the muscle fibres. These did not show any clearly preferred localisation. In the eye, atrophy of the ciliary body was found.
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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