DeCure for Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures — 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 moduleAutosomal dominant childhood-onset proximal spinal muscular atrophy with contractures 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 autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures 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
BICD cargo adaptor 2 (BICD2) — BICD2 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 6PSE · 2.404 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1985 study of 354 cases of chronic proximal spinal muscular atrophy of childhood and adolescence concluded the condition is not as homogeneous as previously thought and proposed a tentative classification based on sex and age at clinical onset. A 1976 report described a family with juvenile proximal spinal muscular atrophy with dominant inheritance and complete penetrance across three generations, noting high variation in age of onset and progression and constant involvement of facial nuclei. A 1986 paper described three patients from a large pedigree with autosomal dominant spinal muscular atrophy manifesting between the fourth and sixth decade, progressing rapidly so that within three years the patients died from respiratory failure, without corticospinal tract dysfunction.
A 1981 review of 44 patients with chronic infantile and juvenile forms of spinal muscular atrophy, followed for an average of 17 years after diagnosis, recommended a specific programme of care for each of four functional groups based on maximal physical function, to anticipate and treat secondary deformity of limbs and spine. A 2002 case report described a newborn boy with severe spinal muscular atrophy, congenital bone fractures, and extremely thin ribs but without contractures; the authors noted that 96% of spinal muscular atrophy type I cases are caused by deletions or mutations in the SMN1 gene on chromosome 5q, but that chromosome 5q-negative patients with additional features such as respiratory distress or cerebellar hypoplasia have been designated as infantile spinal muscular atrophy plus forms.
A 2025 survey of Dutch paediatric rehabilitation physicians caring for children with spinal muscular atrophy receiving disease-modifying treatments found that all respondents agreed that optimal sitting posture was an important treatment goal, 95% agreed on pain prevention, and 87% on maintaining function. Physicians recommended daily use of hand splints less frequently in children who started disease-modifying treatment before symptom onset (35%) than in children who started at an advanced disease stage (54%). Thematic analysis revealed three themes shaping clinical reasoning: functional prognosis as a key element, clinical uncertainty regarding contracture intervention, and incorporation of contextual factors. The physicians described challenges in clinical decision-making due to limited clinical experience and the evolving understanding of disease trajectories in the early post-treatment era.
What is still missing is prospective data on long-term functional outcomes in children treated before symptom onset, randomised trials comparing different contracture management strategies in the disease-modifying treatment era, and validated tools to stratify patients by functional prognosis at the time of treatment initiation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Bone and Joint Surgery - British Volume · 1981 · 116 citations
Functional classification and orthopaedic management of spinal muscular atrophy
AbstractThe majority of patients with chronic infantile and juvenile forms of spinal muscular atrophy survive to adult life. Forty-four patients have been reviewed at an average of 17 years after diagnosis. The subdivision of patients into four groups, based on the maximal physical function developed by the individual, correlates well with the onset and severity of secondary deformity of the limbs and spine. This information allows anticipation of the problems and plans for their treatment to be made from early childhood. After analysis of the orthotic and surgical treatment received by these patients, a specific programme of care is recommended for each of the functional groups.
Severe Spinal Muscular Atrophy Variant Associated With Congenital Bone Fractures
AbstractInfantile autosomal recessive spinal muscular atrophy (type I) represents a lethal disorder leading to progressive symmetric muscular atrophy of limb and trunk muscles. Ninety-six percent cases of spinal muscular atrophy type I are caused by deletions or mutations in the survival motoneuron gene (SMNI) on chromosome 5q11.2-13.3. However, a number of chromosome 5q-negative patients with additional clinical features (respiratory distress, cerebellar hypoplasia) have been designated in the literature as infantile spinal muscular atrophy plus forms. In addition, the combination of severe spinal muscular atrophy and neurogenic arthrogryposis has been described. We present clinical, molecular, and autopsy findings of a newborn boy presenting with generalized muscular atrophy in combination with congenital bone fractures and extremely thin ribs but without contractures.
Journal of Medical Genetics · 1985 · 22 citations · open access
Chronic proximal spinal muscular atrophy of childhood and adolescence: problems of classification and genetic counselling.
AbstractResults obtained from a study of 354 cases of chronic proximal spinal muscular atrophy of childhood and adolescence suggest that the condition is not as homogeneous as it was previously thought. A tentative classification based on our results is proposed. Estimates of genetic risks are provided, taking into account the sex and age at clinical onset. In our opinion these factors are more reliable than the data hitherto available because they are based on a considerably larger series.
A rapidly progressive autosomal dominant scapulohumeral form of spinal muscular atrophy
AbstractThree patients from a large pedigree are described who had autosomal dominant spinal muscular atrophy that became manifest between the end of the fourth and the sixth decade. The disease progressed rapidly without evidence of corticospinal tract dysfunction, and within 3 years the patients died from respiratory failure.
Journal of Medical Genetics · 1976 · 8 citations · open access
A family of juvenile proximal spinal muscular atrophy with dominant inheritance.
AbstractA family with juvenile proximal spinal muscular atrophy with dominant inheritance and complete penetrance is reported. The disease occurred in three generations and showed high variations in the age of onset and progression among the affected members. A characteristic feature was the constant involvement of facial nuclei.
Table 1_Dutch rehabilitation physicians’ perspectives on contracture management in children with spinal muscular atrophy: challenges in a changing landscape.docx
AbstractBackground Many children with hereditary proximal spinal muscular atrophy (SMA) develop joint contractures. With the introduction of disease-modifying treatments (DMTs) for SMA, the improved functional prognosis may change the focus of (preventive) contracture management. Objective This study aimed to describe current approaches to contracture management among Dutch pediatric rehabilitation physicians caring for children with SMA receiving DMT, and to explore the underlying considerations and clinical reasoning that inform their decisions on contracture management in the evolving therapeutic landscape. Methods All registered pediatric rehabilitation physicians (n = 151) received a survey, addressing two main topics: (1) indication and purpose of contracture management, and (2) alignment of clinical decision-making with current guidelines. To this end, three standardized case scenarios were presented. Respondents were asked to indicate whether their current choices, were consistent with the guideline recommendations. To obtain a deeper understanding of the considerations and clinical reasoning regarding contracture management in the era of DMTs, we held an advisory group meeting. We audio-recorded the discussions and analyzed the content thematically. Results The response rate was 56%; 41 of these respondents were not involved in SMA care. 38 of the 44 surveys, completed by participants involved in SMA care, were suitable for analysis. All respondents (strongly) agreed about ‘optimal sitting posture’ being an important treatment goal, 95% agreed on ‘pain prevention’ and 87% on ‘maintaining function’. Physicians recommended daily use of hand splints less frequently in children who started DMT before onset of symptoms (35%) than in children who started DMT at an advanced disease stage (54%). Thematic analysis revealed three themes shaping clinical reasoning: (1) functional prognosis as key element in decision-making; (2) clinical uncertainty regarding contracture intervention; and (3) incorporation of contextual factors. Conclusion Dutch pediatric rehabilitation physicians describe challenges in clinical decision-making regarding contracture management in a changing landscape for SMA. The use of key principles could facilitate the process, including: (1) assessing the child’s functional prognosis; (2) engaging in open discussions with parents about uncertainties arising from limited clinical experience and the evolving understanding of disease trajectories in the early post-DMT era; and (3) applying the ICF framework to incorporate contextual factors into clinical decision-making regarding contracture management.
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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