DeCure for Spastic paraplegia 90B, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 90B, autosomal recessive — 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 90B, autosomal recessive 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 90b, autosomal recessive 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
Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of disorders. Autosomal dominant forms include SPG3A and SPG4. In a 2006 study of 106 families with autosomal dominant HSP, SPG3A mutations were found in seven families and were twice as frequent as SPG4 in patients with onset before age 10 years (31.8%). Later onset was not observed in SPG3A families. The phenotype was pure HSP, but disease duration was longer than in non-SPG3A/SPG4 patients, leading ultimately to greater handicap. A 2000 study reported a family with pure autosomal dominant HSP due to a novel SPG4 splice-site mutation; intrafamilial variability ranged from severe congenital presentation to mild involvement after age 55. A 2020 study identified five HSP pedigrees: two with autosomal dominant SPG4 (SPAST gene variants c.1196C>T and c.1523T>A, the latter previously unreported, with incomplete penetrance in one pedigree), and three with autosomal recessive forms — SPG35 (FA2H gene compound heterozygous variants c.61G>C and c.688G>A), SPG11 (compound heterozygous variants c.6812+4_6812+7delAGTA and c.915delT), and SPG7 (compound heterozygous variants c.1703_1704delAG and c.1937-1G>C). All variants were predicted likely pathogenic by ACMG criteria.
Autosomal recessive HSP with thin corpus callosum (HSP-TCC) is a common complicated subtype. A 2006 study mapped two consanguineous families with complicated ARHSP to a new locus on 8p12-p11.21 (9 cM interval between markers D8S1820 and D8S532, combined lod score 7.077 at D8S505). Affected individuals in one family had thin corpus callosum and mental retardation; in the other family two of three affected individuals had epilepsy. Neuregulin and KIF13B were noted as candidate genes. A 2005 report described childhood onset of HSP-TCC in two patients, but provided no genetic or quantitative clinical data. A 1988 series of six families (26 affected members) noted that all initial referrals were children with slowly progressive paraplegia, slightly delayed motor milestones, normal intellect, and no perinatal cerebral event; the authors emphasised that recognition of the hereditary pattern is key to management.
No drug treatment, clinical trial, or therapeutic intervention for any form of HSP is mentioned in any of these abstracts. No quantitative survival or response rates are reported. What is missing for any potential drug-repurposing effort is a clear molecular target validated in patients, a defined patient stratification by genotype (SPG3A, SPG4, SPG7, SPG11, SPG35, or the 8p locus), and funding for preclinical models or a clinical trial. The abstracts provide no data on disease progression rates, biomarkers, or outcome measures that could be used to design a trial.
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 · 119 citations
SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years
AbstractSeven families with six different SPG3A mutations were identified among 106 with autosomal dominant hereditary spastic paraplegia (HSP). Two mutations were novel (T162P, C375R). SPG3A was twice as frequent as SPG4 in patients with onset before age 10 years (31.8%). Later onset was not observed. The phenotype was pure HSP, but disease duration was longer than in non-SPG3A/SPG4 patients, leading ultimately to greater handicap.
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.
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.
[Clinical characteristics and variant analysis of five pedigrees with hereditary spastic paraplegia].
AbstractOBJECTIVE: To explore the clinical and genetic characteristics of five pedigrees affected with hereditary spastic paraplegia(HSP). METHODS: Clinical data of the five pedigrees was collected, and high-throughput sequencing was carried out to detect potential variants. Sanger sequencing were used to verify the results. RESULTS: The probands of pedigree 1 and 2 were found to harbor heterozygous SPAST gene variants, namely c.1196C>T and c.1523T>A. The proband of pedigree 3 harbored compound heterozygous variants of FA2H gene (c.61G>C and c.688G>A). Proband from pedigree 4 harbored compound heterozygous variants of SPG11 gene (c.6812+4_6812+7delAGTA and c.915delT). The proband of pedigree 5 harbored compound heterozygous variants of SPG7 gene (c.1703_1704delAG and c.1937-1G>C). Based on the American College of Medical Genetics and Genomics(ACMG) guidelines, all variants were predicted to be likely pathogenic. Among these, SPAST gene c.1523T>A, FA2H gene c.61.G>C, SPG11 gene splicing region c.6812+4_6812+7delAGTA, c.915delT, SPG7 gene c.1703_1704delAG and splicing region c.1937-1G>C variants were unreported previously. CONCLUSION: The probands of pedigrees 1 and 2 were diagnosed with autosomal dominant hereditary spastic paraplegia type 4, for which pedigree 2 showed incompletely penetrance. Pedigrees 3, 4, and 5 were diagnosed with autosomal recessive hereditary spastic paraplegia type 35, 11 and 7, respectively. Above result provided a reference for clinical diagnosis and genetic counseling for the affected pedigrees.
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.
