DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary spastic paraplegia 10 — 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 moduleHereditary spastic paraplegia 10 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 hereditary spastic paraplegia 10 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
kinesin family member 5A (KIF5A) — KIF5A 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 gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4UXY · 6.5 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary spastic paraplegia is a genetically transmitted disease, usually autosomal dominant, characterised by slow progression of spastic paraparesis. In a 1988 series of six families with 26 affected members, all initial referrals were children with slowly progressive paraplegia, slightly delayed motor milestones, normal intellect, and no history of perinatal cerebral event. The authors stated that recognition is the key to management and that a careful family history reveals the hereditary nature. No drug treatment was reported in that series; management consisted of tendon lengthenings when necessary.
In Caucasian populations, heterozygous Spastin mutations account for the majority of patients (SPG4), with predominant clinical manifestation in the third or fourth decade. Childhood manifestation is more common in less frequent forms such as SPG3a or complicated HSP like SPG11, according to a 2015 review. No drug intervention was tested or recommended in that paper.
A 2025 study assessed health-related quality of life in 80 children with rare hereditary spastic paraplegias using the Caregiver Priorities and Child Health Index of Life with Disabilities. HRQoL was consistently reduced, particularly for motor, autonomic, and bulbar symptoms. Children with complex HSP phenotypes had lower scores than those with pure forms. Scores correlated with established clinical scales but declined with age only in HSP-SPG11 and HSP-ZFYVE26. The study identified determinants of reduced quality of life and highlighted clinical targets for supportive interventions, but it did not test any drug. The trial was registered as NCT04712812, a registry and natural history study for early onset hereditary spastic paraplegia.
No abstract in this set reports a drug trial, a repurposed compound, or any pharmacological intervention for hereditary spastic paraplegia 10 specifically. What is still missing is any randomised controlled trial of a drug for this condition, funding for such a trial, and a clear patient stratification strategy that would allow a meaningful test of a candidate therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
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.
Annals of Clinical and Translational Neurology · 2025 · 0 citations · open access
Health‐Related Quality of Life in Rare Forms of Childhood‐Onset Hereditary Spastic Paraplegia
AbstractWe assessed health-related quality of life (HRQoL) in 80 children with rare hereditary spastic paraplegias using the Caregiver Priorities and Child Health Index of Life with Disabilities and clinician-reported outcomes. HRQoL was consistently reduced, particularly in relation to motor, autonomic, and bulbar symptoms. Children with complex HSP phenotypes had lower scores than those with pure forms. Scores correlated with established clinical scales but declined with age only in HSP-SPG11 and HSP-ZFYVE26. These findings identify key determinants of reduced quality of life and highlight clinical targets for supportive interventions in childhood-onset hereditary spastic paraplegia. Trial Registration: Registry and Natural History Study for Early Onset Hereditary Spastic Paraplegia: NCT04712812.
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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