DeCure for Spastic paraplegia 72b, autosomal recessive
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 72b, autosomal recessive — screening already-approved drugs against its 2-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 72b, autosomal recessive maps to a 2-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 72b, 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
glutamate ionotropic receptor delta type subunit 2 (GRID2) — GRID2 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 9NWO · 3.57 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Spastic paraplegia 72b is not mentioned in any of the provided abstracts. The abstracts instead describe SPG3A, a locus on chromosome 8p12-p11.21 for autosomal recessive HSP with thin corpus callosum and epilepsy, SPG77 caused by FARS2 mutations, and HSP with thin corpus callosum in two childhood-onset patients. In 2006, seven families with six different SPG3A mutations were identified among 106 with autosomal dominant HSP; SPG3A was twice as frequent as SPG4 in patients with onset before age 10 years (31.8%), and 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.
Two consanguineous families with complicated autosomal recessive HSP were mapped to a new locus on 8p12-p11.21, 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. Neuregulin and KIF13B genes were noted as interesting functional candidates. In 2024, two affected siblings in an autosomal recessive spastic paraplegia family were reported with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2, causing spastic paraplegia type 77. Both patients gradually developed altered gaits and weakness in both lower limbs; the literature review noted high heterogeneity in clinical manifestations of SPG77.
No abstract provides any data on treatment, drug repurposing, or clinical trials for spastic paraplegia 72b or any other HSP subtype. What is missing for any of these genetic forms is a clear molecular target for a drug, any preclinical or clinical testing of a candidate compound, and patient stratification by specific mutation. Funding for natural history studies and for developing cellular or animal models of the specific genetic subtypes would be needed before any drug could be evaluated.
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.
Annals of Clinical and Translational Neurology · 2024 · 2 citations · open access
A pseudo‐homozygous missense variant and <i>Alu</i>‐mediated exon 5 deletion in <scp><i>FARS2</i></scp> causing spastic paraplegia 77
AbstractFARS2-associated hereditary spastic paraplegia, later onset spastic paraplegia type 77, is a rarely neurodegenerative disease. Here, we reported two affected siblings in an autosomal recessive spastic paraplegia family with a pseudo-homozygous missense variant and Alu-mediated exon 5 deletion in FARS2. Both patients gradually developed altered gaits and weakness in both lower limbs. In our literature review, spastic paraplegia type 77 shows high heterogeneity in clinical manifestations. Our study broadens the scope of pathogenic mechanisms of SPG77 resulting from compound heterozygous mutations in FARS2 and provides strong evidence that deletion in FARS2 due to recombination event mediated by Alu element.
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.
Partial agenesis of the corpus callosum in spastin related hereditary spastic paraplegia
AbstractCase report: We report a family with four affected individuals in three generations, suffering from autosomal dominant hereditary spastic paraplegia (HSP). All patients show the typical symptoms of pure HSP including spasticity and hyperreflexia of the lower limbs, calf crambs, pallhypaesthesia of the lower limbs and clinical signs of an affection of the dorsal columnes. To comprehend a mild cognitive impairment, we performed a neuropsychological evaluation including the Trail Making Test, the Digit Symbol Test, the Digit Span Test and the Controlled Oral Word Association Test. Cognitive functions of all patients were unaffected. For signs of a depressive syndrome, we used the Beck Depression Inventary (BDI). One patient showed a mild depressive syndrome in the past, the other patients were unaffected.
[Advance of research on Hereditary spastic paraplegia type 4].
AbstractSpastic paraplegia type 4 (SPG4) is the most common type of autosomally inherited spastic paraplegia. Its main clinical features include typical simple hereditary spastic paraplegia, with neurological impairments limited to lower limb spasticity, hypertonic bladder dysfunction, and mild weakening of lower limb vibration sensation, without accompanying features such as nerve atrophy, ataxia, cognitive impairment, seizures, and muscle tone disorders. SPAST is the main pathogenic gene underlying SPG4, and various pathogenic SPAST variants have been discovered. This disease has featured a high degree of clinical heterogeneity, and the same pathogenic variant can have different age of onset and severity among different patients and even within the same family. There is a lack of systematic research on the correlation between the genotype and phenotype of SPG4, and the pathogenic mechanism has remained controversial. This article has provided a review for the clinical characteristics, pathogenic gene characteristics, correlation between the genotype and phenotype, and pathogenic mechanism of this disease, with an aim to provide reference for its clinical diagnosis and treatment.
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.
