DeCure for Spastic paraplegia 90A, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 90A, autosomal dominant — 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 moduleSpastic paraplegia 90A, autosomal dominant 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 spastic paraplegia 90a, autosomal dominant 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
serine palmitoyltransferase small subunit A (SPTSSA) — SPTSSA 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 vsddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7K0K · 2.6 Å · ligand 3-Dehydrosphinganine (VSD). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not describe any drug treatment for spastic paraplegia 90A, autosomal dominant. The 2015 study of continuous intrathecal baclofen (ITB) pump therapy included nine patients with hereditary spastic paraplegia (HSP), but does not specify which genetic subtype. After ITB therapy, improvements were seen in rectus femoris spasticity (P=0.04) and gastrocnemius spasticity (P=0.03). All nine patients reported subjective functional improvements, and three of four with pre- and post-pump assessments showed clinically meaningful mobility improvements. The study is retrospective, with no control group, and does not address the autosomal dominant SPG90A form.
The remaining abstracts concern genetic mapping and clinical description of HSP. A 2006 paper mapped a new locus for autosomal recessive HSP with thin corpus callosum and epilepsy to chromosome 8p12-p11.21 in two consanguineous families. A 2000 paper identified a novel SPG4 mutation in a family with pure autosomal dominant HSP showing wide variability in age at onset and severity. A 1988 report described six families with autosomal dominant HSP, noting frequent misdiagnosis as cerebral palsy. A 1981 pedigree study of autosomal dominant HSP reported late onset, reduced penetrance, and variable expression.
No abstract mentions any drug tested specifically for spastic paraplegia 90A, autosomal dominant. The baclofen study is the only treatment-related evidence, but it does not stratify patients by genetic diagnosis. What is missing is any clinical trial of a drug in patients with a confirmed SPG90A mutation, any preclinical work in models of that specific genetic form, and any funding or trial design aimed at this rare autosomal dominant subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2006 · 52 citations
A novel locus for hereditary spastic paraplegia with thin corpus callosum and epilepsy
AbstractBACKGROUND: Hereditary spastic paraplegia (HSP) are classified clinically as pure when progressive spasticity occurs in isolation or complicated when other neurologic abnormalities are present. At least 22 genetic loci have been linked to HSP, 8 of which are autosomal recessive (ARHSP). HSP complicated with the presence of thin corpus callosum (HSP-TCC) is a common subtype of HSP. One genetic locus has been identified on chromosome 15q13-q15 (SPG11) for HSP-TCC, but some HSP-TCC families have not been linked to this locus. METHODS: The authors characterized two families clinically and radiologically and performed a genome-wide scan and linkage analysis. RESULTS: The two families had complicated ARHSP. The affected individuals in Family A had thin corpus callosum and mental retardation, whereas in Family B two of three affected individuals had epilepsy. In both families linkage analysis identified a locus on chromosome 8 between markers D8S1820 and D8S532 with the highest combined lod score of 7.077 at marker D8S505. This 9 cM interval located on 8p12-p11.21 represents a new locus for ARHSP-TCC. Neuregulin and KIF13B genes, located within this interval, are interesting functional candidate genes for this HSP form. CONCLUSION: Two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia were clinically characterized and genetically mapped to a new locus on 8p12-p11.21.
Intrafamilial variability in hereditary spastic paraplegia associated with an <i>SPG4</i> gene mutation
AbstractThe authors studied a family with pure autosomal dominant spastic paraplegia (ADHSP) that showed a marked intrafamilial variability in both age at onset and clinical severity, ranging from severe congenital presentation to mild involvement after age 55. They found a novel mutation in the SPG4 gene, which segregates with the disease in six patients. The mutation affects the consensus donor splice site of SPG4 intron 16, resulting in a premature termination codon at amino acid 578. The data confirm the pathologic significance of SPG4 mutations in pure ADHSP and add to the list of known SPG4 allelic variants.
Journal of Pediatric Orthopaedics · 1988 · 11 citations
Hereditary Spastic Paraplegia
AbstractHereditary spastic paraplegia is a genetically transmitted disease that is usually autosomal dominant. Characterized by a slow progression of spastic paraparesis, it is frequently misdiagnosed as cerebral palsy. Our experience consists of six families with a total of 26 affected members. All initial referrals were children with a slowly progressive paraplegia. Each child was noted to have slightly delayed motor milestones, normal intellect, and no history of perinatal cerebral event. Each child was treated when necessary with appropriate tendon lengthenings. Recognition is the key to management. A careful patient and family history will reveal the hereditary nature of the disease and help develop treatment plans.
Slowly progressive autosomal dominant spastic paraplegia with late onset, variable expression and reduced penetrance: a basis for diagnosis and counseling
AbstractWe have examined a pedigree in which familial spastic paraplegia (FSP) is segregating in four generations. The data show a high rate of transmission of the trait, late onset, reduced penetrance, variable age and symptom expressivity, and an autosomal dominant mode of transmission. A summary of our data together with the FSP data of other shows a 1:1 transmission from males and from females, and an overall 1:1 transmission ratio. The risks for the children of symptomatic and non-symptomatic parents are illustrated.
Use of continuous intrathecal baclofen in hereditary spastic paraplegia
AbstractObjective: Hereditary spastic paraplegia (HSP) is a rare progressive disorder with few treatment options. We aim to describe the effect of continuous intrathecal baclofen (ITB) pump therapy on the clinical and functional outcomes of patients with HSP. Methods: This is a retrospective study, using medical record audit data. Adult patients with HSP who had received ITB trial or therapy and had pre- and post-ITB assessment data available were eligible for inclusion. A purposefully designed audit tool was used. Patients with a successful trial received an ITB implantable SynchroMed ® II pump. Demographic, clinical, and outcome data were obtained pre- and post-pump trial and pump insertion. Functional, spasticity, and mobility measures were compared pre- and post-ITB trial and pre- and post-ITB pump insertion. Results: Data for nine patients were available. Six were male and the median age was 55 years (Q1, Q3: 46, 55). All received an ITB trial, and those who responded favorably (n=8) had an ITB pump inserted. Following ITB therapy, improvements were demonstrated for rectus femoris ( P =0.04) and gastrocnemius spasticity measures ( P =0.03). All patients reported subjective improvements in function, and three of the four with pre- and post-pump assessments, demonstrated clinically meaningful improvements in mobility. Side effects were minimized with appropriate dose titrations. Conclusion: This is the largest retrospective patient study in the field. The potential benefits of ITB in selected patients with HSP were demonstrated. Keywords: baclofen, intrathecal baclofen, hereditary spastic paraplegia, gait analysis
Hereditary spastic paraplegia with thin corpus callosum – childhood onset in two patients
AbstractBackground: The hereditary spastic paraplegias (HSPs) are a group of rare disorders with the predominant clinical feature of spastic gait. They are subdivided into pure and complicated forms according to whether the disorder is associated with other neurologic abnormalities. Autosomal dominant, recessive and X-linked forms of HSP have been defined.
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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