DeCure for Spastic paraplegia 18a, autosomal dominant
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 18a, autosomal dominant — 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 18a, autosomal dominant 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 18a, autosomal dominant 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
ER lipid raft associated 2 (ERLIN2) — ERLIN2 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 9O9U · 3.0 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
SPG3A is the most frequent cause of hereditary spastic paraplegia with onset before age 10 years. Among 106 families with autosomal dominant HSP, seven families carried six different SPG3A mutations, two of which were novel (T162P, C375R). In patients with onset before age 10, SPG3A was twice as frequent as SPG4 (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 retrospective study of nine patients with HSP who received continuous intrathecal baclofen (ITB) pump therapy reported improvements in rectus femoris spasticity (P=0.04) and gastrocnemius spasticity (P=0.03) following ITB therapy. Eight of nine patients responded favourably to an ITB trial and had a pump inserted. All patients reported subjective improvements in function, and three of four with pre- and post-pump assessments showed clinically meaningful improvements in mobility. Side effects were minimised with dose titrations. The study was retrospective, small, and did not include a control group.
A Korean single-centre study reviewed 69 patients with spastic paraplegia from 54 unrelated families over 22 years. The median age of symptom onset was 25 years (interquartile range 14.0–37.0). Fifty-one patients (74%) presented with the pure form. Spastic gait was universal. Urinary dysfunction occurred in 42 patients (61%). Additional neurologic manifestations included peripheral neuropathy (13%), cognitive impairment (7%), upper limb weakness (6%), dysarthria (6%), dysphagia (4%), ataxia (4%), and scoliosis (3%). Brain MRI showed thin corpus callosum in two patients with SPG11; all patients with SPG4 had normal findings. Spine MRI revealed spinal cord atrophy in 16 patients (27%), including six with SPG4. The most prevalent causative gene was SPAST (SPG4), detected in 26 families. Seven novel pathogenic variants were identified.
Two consanguineous families with complicated autosomal recessive HSP and thin corpus callosum were mapped to a new locus on 8p12-p11.21, a 9 cM interval between markers D8S1820 and D8S532. 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 genes within this interval were noted as functional candidate genes. What remains missing are prospective controlled trials of intrathecal baclofen in HSP, larger genetically characterised cohorts to stratify outcomes by mutation type, and any disease-modifying therapy for any form of HSP.
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.
Use of continuous intrathecal baclofen in hereditary spastic paraplegia
AbstractObjective: Hereditary spastic paraplegia (HSP) is a rare progressive disorder with few treatment options. We aim to describe the effect of continuous intrathecal baclofen (ITB) pump therapy on the clinical and functional outcomes of patients with HSP. Methods: This is a retrospective study, using medical record audit data. Adult patients with HSP who had received ITB trial or therapy and had pre- and post-ITB assessment data available were eligible for inclusion. A purposefully designed audit tool was used. Patients with a successful trial received an ITB implantable SynchroMed ® II pump. Demographic, clinical, and outcome data were obtained pre- and post-pump trial and pump insertion. Functional, spasticity, and mobility measures were compared pre- and post-ITB trial and pre- and post-ITB pump insertion. Results: Data for nine patients were available. Six were male and the median age was 55 years (Q1, Q3: 46, 55). All received an ITB trial, and those who responded favorably (n=8) had an ITB pump inserted. Following ITB therapy, improvements were demonstrated for rectus femoris ( P =0.04) and gastrocnemius spasticity measures ( P =0.03). All patients reported subjective improvements in function, and three of the four with pre- and post-pump assessments, demonstrated clinically meaningful improvements in mobility. Side effects were minimized with appropriate dose titrations. Conclusion: This is the largest retrospective patient study in the field. The potential benefits of ITB in selected patients with HSP were demonstrated. Keywords: baclofen, intrathecal baclofen, hereditary spastic paraplegia, gait analysis
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.
Yonsei Medical Journal · 2025 · 0 citations · open access
Comprehensive Characterization of Spastic Paraplegia in Korean Patients: A Single-Center Experience over Two Decades
AbstractPURPOSE: Hereditary spastic paraplegia (HSP) refers to a group of genetic neurodegenerative diseases marked by gradually worsening spasticity and hyperreflexia in the lower extremities. This study aimed to describe the clinical and genetic characteristics of Korean patients with spastic paraplegia. MATERIALS AND METHODS: We retrospectively reviewed medical records of 69 patients with spastic paraplegia from 54 unrelated families between 2002 and 2024. Genetic, clinical, electrophysiological, and radiological features were comprehensively analyzed. RESULTS: , detected in 26 families, was the most prevalent. Seven novel pathogenic variants were identified. Clinically, the median age of symptom onset was 25 years [14.0-37.0]. Out of 69 patients with spastic paraplegia, 51 (74%) presented with the pure form of spastic paraplegia, which included all patients with SPG4. Spastic gait was a universal feature in all patients. Urinary dysfunction was present in 42 (61%) patients. Additional neurologic manifestations included peripheral neuropathy 9 (13%), cognitive impairment 5 (7%), upper limb weakness 4 (6%), dysarthria 4 (6%), dysphagia 3 (4%), ataxia 3 (4%), and scoliosis 1 (3%). Brain MRI findings demonstrated a thin corpus callosum in two patients with SPG11; all patients with SPG4 had normal findings. Spine MRI revealed spinal cord atrophy in 16 (27%) patients, including 6 (21%) patients with SPG4. CONCLUSION: as the causative gene and underscoring the genetic and phenotypic heterogeneity of spastic paraplegia.
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.
