DeCure for Autosomal recessive complex spastic paraplegia type 9B
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for autosomal recessive complex spastic paraplegia type 9B — 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 recessive complex spastic paraplegia type 9B 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 recessive complex spastic paraplegia type 9b 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
aldehyde dehydrogenase 18 family member A1 (ALDH18A1) — ALDH18A1 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 2H5G · 2.25 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2006 study of two consanguineous families with complicated autosomal recessive hereditary spastic paraplegia mapped a new locus to chromosome 8p12-p11.21. The highest combined lod score was 7.077 at marker D8S505. Affected individuals in one family had thin corpus callosum and mental retardation; in the other family, two of three affected individuals had epilepsy. The candidate genes noted were neuregulin and KIF13B. This locus is distinct from the previously identified SPG11 locus on chromosome 15q13-q15.
A 2000 study of a family with pure autosomal dominant spastic paraplegia found a novel mutation in the SPG4 gene. The mutation affected the consensus donor splice site of intron 16, producing a premature termination codon. Intrafamilial variability was marked, with age at onset and severity ranging from severe congenital presentation to mild involvement after age 55. That study concerns a different inheritance pattern and gene from the disease in question.
A 2019 review notes that about 80 spastic paraplegia genes exist, with almost 70 identified. Common autosomal recessive forms listed are SPG11, SPG7, and SPG15. The disease in question, autosomal recessive complex spastic paraplegia type 9B, is not among the common forms described in that review, and no specific treatment or drug is mentioned in any of these abstracts.
No drug, no trial, and no intervention of any kind appears in these abstracts for this disease. What is missing is any clinical trial, any patient stratification, any funding for natural history studies or gene-specific therapy development for the SPG9B locus.
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 · 2008 · 57 citations
A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23
AbstractBACKGROUND: The hereditary spastic paraplegias (HSPs) are a group of clinically and genetically heterogeneous neurodegenerative disorders in which the cardinal pathologic feature is upper motor neuron degeneration leading to progressive spasticity and weakness of the lower limbs. To date, 14 autosomal recessive HSP loci have been mapped. METHODS: We have identified a large consanguineous Omani family in which an autosomal recessive form of HSP is segregating. The age at onset varied from 6 to 11 years and the course of the disease is progressive with intellectual disability and is associated with seizures in two individuals. To map the chromosomal location of the causative gene we undertook 250K gene chip SNP analyses of all affected individuals assuming that a founder mutation was responsible. RESULTS: All affected individuals shared a 20.4 Mb (3.25 cM) region of homozygosity located on chromosome 16q21-q23.1, defined by SNP markers rs149428 and rs9929635 (peak multipoint lod score of 4.86). Two candidate genes, dynein, cytoplasmic 1, light intermediate chain 2 (DYNC1LI2) and vacuolar protein sorting 4 homolog A (VPS4A), were sequenced but no disease causing mutations were identified. CONCLUSION: We have mapped the chromosomal location of a novel gene responsible for a form of hereditary spastic paraplegia (HSP) (SPG35) and defined its clinical presentation.
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.
S S Korsakov Journal of Neurology and Psychiatry · 2019 · 5 citations
Common forms of hereditary spastic paraplegias
AbstractA group of hereditary spastic paraplegias includes about 80 spastic paraplegia genes (SPG): forms with identified (almost 70) or only mapped (about 10) genes. Methods of next generation sequencing (NGS), along with new SPG discovering, modify knowledge about earlier delineated SPG. Clinical and genetic characteristics of common autosomal dominant (SPG4, SPG3, SPG31) and autosomal recessive (SPG11, SPG7, SPG15) forms are presented.
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.
