DeCure for Spastic paraplegia 30B, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 30B, 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 30B, 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 30b, 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
kinesin family member 1A (KIF1A) — KIF1A 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 8UTS · 2.7 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
The 2006 study mapped a new genetic locus for autosomal recessive hereditary spastic paraplegia with thin corpus callosum and epilepsy to chromosome 8p12-p11.21 in two consanguineous families. The linked interval spanned 9 cM between markers D8S1820 and D8S532, with a combined lod score of 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 authors proposed neuregulin and KIF13B as functional candidate genes within that interval. No drug or treatment was tested.
A 2019 guideline on managing spasticity in hereditary spastic paraplegia acknowledged that there is a lack of evidence base and guidance for anti-spasticity drugs. The guideline was based on expert consultation and regional practice (Level D evidence) supported by Level A-C evidence for individual treatments. It recommended early and regular physical rehabilitation and ankle-foot orthoses. Oral baclofen was listed as first-line anti-spasticity drug, followed by gabapentin and tizanidine. Intrathecal baclofen in selected patients showed promising results and should be considered early if oral medication fails. The evidence for botulinum toxin in HSP was described as limited and unclear. Selective dorsal rhizotomy was not routinely offered and should be considered only for uncomplicated stable HSP when all other treatments have failed. The guideline also stated that a trial of dopamine should be considered if the diagnosis of HSP is in doubt, and that some forms of HSP have shown response to dopamine. No specific response rates, survival data, or sample sizes were given.
A 2020 study of five HSP pedigrees used high-throughput sequencing to identify likely pathogenic variants. Among the autosomal recessive cases, pedigree 3 carried compound heterozygous FA2H gene variants (c.61G>C and c.688G>A) and was diagnosed with HSP type 35. Pedigree 4 carried compound heterozygous SPG11 gene variants (c.6812+4_6812+7delAGTA and c.915delT) and was diagnosed with HSP type 11. Pedigree 5 carried compound heterozygous SPG7 gene variants (c.1703_1704delAG and c.1937-1G>C) and was diagnosed with HSP type 7. Several of these variants were previously unreported. No treatment or clinical outcomes were reported.
What is still missing for spastic paraplegia 30B specifically: no clinical trial has tested any drug for this subtype, no patient stratification by genotype has been attempted, and no funding for a dedicated natural history study or treatment trial is evident in these abstracts. The 2019 guideline relies on expert opinion rather than randomised evidence for HSP generally, and no abstract addresses SPG30B by name.
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.
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.
[Clinical characteristics and variant analysis of five pedigrees with hereditary spastic paraplegia].
AbstractOBJECTIVE: To explore the clinical and genetic characteristics of five pedigrees affected with hereditary spastic paraplegia(HSP). METHODS: Clinical data of the five pedigrees was collected, and high-throughput sequencing was carried out to detect potential variants. Sanger sequencing were used to verify the results. RESULTS: The probands of pedigree 1 and 2 were found to harbor heterozygous SPAST gene variants, namely c.1196C>T and c.1523T>A. The proband of pedigree 3 harbored compound heterozygous variants of FA2H gene (c.61G>C and c.688G>A). Proband from pedigree 4 harbored compound heterozygous variants of SPG11 gene (c.6812+4_6812+7delAGTA and c.915delT). The proband of pedigree 5 harbored compound heterozygous variants of SPG7 gene (c.1703_1704delAG and c.1937-1G>C). Based on the American College of Medical Genetics and Genomics(ACMG) guidelines, all variants were predicted to be likely pathogenic. Among these, SPAST gene c.1523T>A, FA2H gene c.61.G>C, SPG11 gene splicing region c.6812+4_6812+7delAGTA, c.915delT, SPG7 gene c.1703_1704delAG and splicing region c.1937-1G>C variants were unreported previously. CONCLUSION: The probands of pedigrees 1 and 2 were diagnosed with autosomal dominant hereditary spastic paraplegia type 4, for which pedigree 2 showed incompletely penetrance. Pedigrees 3, 4, and 5 were diagnosed with autosomal recessive hereditary spastic paraplegia type 35, 11 and 7, respectively. Above result provided a reference for clinical diagnosis and genetic counseling for the affected pedigrees.
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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