DeCure for Spastic paraplegia 92, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 92, 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 92, 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 92, 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
FIC domain protein adenylyltransferase (FICD) — FICD 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 -drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4U04 · 2.48 Å · ligand D(-)-TARTARIC ACID (TAR). Experimental structure, not a prediction.
What the evidence adds up to
The two families described in the 2006 study had complicated autosomal recessive hereditary spastic paraplegia. Family A showed thin corpus callosum and mental retardation; in Family B two of three affected individuals had epilepsy. Linkage analysis mapped a new locus on chromosome 8p12-p11.21, a 9 cM interval between markers D8S1820 and D8S532, with a combined lod score of 7.077 at marker D8S505. The authors noted neuregulin and KIF13B as candidate genes within that interval. No drug or treatment was tested.
A 2005 report described two patients with childhood-onset hereditary spastic paraplegia with thin corpus callosum, but gave no genetic locus, no drug, and no quantitative outcome data. The 1988 paper reported 26 affected members across six families, all initially referred as children with slowly progressive paraplegia, slightly delayed motor milestones, and normal intellect. Treatment was limited to tendon lengthenings when needed; no drug intervention was described. The 1999 study of a large family with pure autosomal dominant HSP found evidence of genetic anticipation consistent with a trinucleotide repeat instability, but again no drug was involved.
No abstract in this set reports any drug trial, any biomarker, any survival or response rate, or any attempt to repurpose an existing compound. The only interventions mentioned are surgical tendon lengthenings from 1988. What is missing for spastic paraplegia 92 specifically is any clinical trial, any patient stratification by genotype, any funding for a drug-repurposing screen, and any preclinical model that could test a candidate molecule against the relevant mutation.
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.
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.
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.
GP116 Approach to managing spasticity in hereditary spastic paraplegia
Abstract<h3>Aim</h3> We aim to provide a guidance in the management of spasticity in children with Hereditary Spastic Paraplegia (HSP). <h3>Introduction</h3> Hereditary spastic paraplegia is a group of clinically and genetically diverse disorders that result in progressive and generally severe lower extremity weakness and spasticity. Spinal and brain MRI and exome sequencing are the most useful investigations for diagnosing HSP. There is a lack of evidence base and guidance for the use of anti-spasticity drugs and uncertainty about the place of other modalities such as intrathecal baclofen (ITB), selective dorsal Rhizotomy (SDR) and botulinum toxin in HSP. <h3>Method</h3> A guideline was prepared based on consultation with experts and regional specialist practice (Level D Evidence) supported by Level A-C evidence for individual treatment options. The guideline includes mode of action, dosage suggestions, side effect profile and cautions for the treatment modalities and summarises key management steps in a flow chart. <h3>Management of spasticity</h3> Management of spasticity in HSP is based on identifying clear and realistic goals in the following three areas: improving mobility, increasing range of motion and relieving spasticity. These goals can be achieved through a combination of physiotherapy, medical agents and, occasionally, surgery. An early and regular physical rehabilitation program is recommended with use of assistive devices such as ankle-foot orthoses. As a first step, a trial of Dopamine should be considered if the diagnosis of HSP is in doubt. Furthermore some forms of HSP have shown response to Dopamine. Oral Baclofen is used as a first-line anti-spasticity drug followed by oral Gabapentin and Tizanidine. Intrathecal baclofen in selected patients has shown promising results; this should be considered early in eligible patients if oral medication is failing to achieve desired spasticity control or side effects limit oral dosing. The evidence for the use of botulinum toxin in HSP is limited and unclear. Its benefits are greatest when combined with therapy and splinting. Diazepam can be used as an adjunct to other oral medications to improve symptom control. Selective Dorsal Rhizotomy is not routinely offered for HSP and should only be considered for uncomplicated stable HSP when all other treatments have failed and quality of life is severely affected. <h3>Conclusion</h3> Managing spasticity well in patients with HSP can immensely improve their quality of life. We propose a standardised referral and management pathway that summarises the approach to medical and surgical options for patients with HSP.
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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