DeCure for Spastic paraplegia 89, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 89, 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 89, 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 89, 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
autocrine motility factor receptor (AMFR) — AMFR 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 oxldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4LAD · 2.3 Å · ligand OXALATE ION (OXL). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not contain any study of spastic paraplegia 89, autosomal recessive. They describe other forms of hereditary spastic paraplegia (HSP). SPG3A, caused by mutations in the ATL1 gene, was the most frequent cause of HSP with onset before age 10 in a study of 106 families with autosomal dominant HSP, accounting for 31.8% of early-onset cases, and was twice as frequent as SPG4 in that age group. Later onset was not observed in SPG3A patients, and the phenotype was pure HSP, though longer disease duration led to greater handicap. A family with a novel SPG4 mutation showed marked intrafamilial variability in age at onset and severity, from severe congenital presentation to mild involvement after age 55. Another large family with pure autosomal dominant HSP showed evidence of genetic anticipation, with earlier onset in successive generations, consistent with a dynamic mutation mechanism.
Screening for mutations in the Pi4k2a gene in 24 index cases of autosomal recessive HSP of unknown genetic cause identified no pathogenic changes in exons or splice sites, suggesting that gene is not a cause of autosomal recessive HSP in humans. Two patients with childhood-onset HSP and thin corpus callosum were described, a feature associated with complicated HSP forms such as SPG11. In Caucasian populations, SPG4 mutations are the most common cause of HSP, with typical onset in the third or fourth decade, while childhood manifestation is more common in SPG3A or complicated forms like SPG11.
No data exist in these abstracts on spastic paraplegia 89, its genetic cause, clinical features, or any drug tested for it. What is missing for this specific disease is any clinical or preclinical research on drug repurposing, a defined patient cohort, and knowledge of the underlying molecular pathology that would allow targeted screening.
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.
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.
American Journal of Medical Genetics · 1999 · 8 citations
Genetic anticipation in a large family with pure autosomal dominant hereditary spastic paraplegia
AbstractWe have reinvestigated a large kindred identified over 25 years ago segregating for a form of pure autosomal dominant hereditary spastic paraplegia (HSP). We have examined additional relatives in order to refine the clinical and genetic characteristics of this disorder, and performed an analysis to determine if anticipation is present in this family. Analysis of onset ages in parent-to-child transmissions of HSP is consistent with anticipation. These results provide support for dynamic mutation as the underlying mechanism of this form of HSP, and suggest a trinucleotide repeat instability occurring primarily in the female germ line.
Screening for mutations in the phosphatidylinositol 4-kinase 2-alpha gene in autosomal recessive hereditary spastic paraplegia
AbstractNumerous genes causing autosomal recessive hereditary spastic paraplegia (AR HSP) have been described. Despite this, in many families the causative gene and mutation are unknown. In this study we sequenced the Pi4k2a gene, whose knockout has been shown to cause a typical HSP model in mice, in 24 index cases of autosomal recessive HSP not known to be linked to any other HSP locus. No pathogenic changes were identified in exons or splice sites, suggesting the Pi4k2a gene may not be a cause of AR HSP in humans.
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.
Mutation Spectrum and Infantile Manifestation in Hereditary Spastic Paraplegia
AbstractAims: Hereditary spastic paraplegia (HSP) is genetically heterogeneous and clinically characterized by gait impairment because of weakness and spasticity of the lower limbs. In Caucasian populations, heterozygous Spastin mutations account for the majority of patients (SPG4) with predominant clinical manifestation within the third or fourth decade of life. A clinical manifestation during childhood is well known, but more common in less frequent forms such as SPG3a or complicated HSP, for example, SPG11.
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.
