DeCure for Spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for spastic paraplegia 91, autosomal dominant, with or without cerebellar ataxia — 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 91, autosomal dominant, with or without cerebellar ataxia 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 91, autosomal dominant, with or without cerebellar ataxia 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
spectrin alpha, non-erythrocytic 1 (SPTAN1) — SPTAN1 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 3FB2 · 2.3 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
In a 2022 Taiwanese cohort of 24 patients (15 male, 9 female) from 22 families with spastic paraparesis combined with cerebellar involvement, median disease onset was 20.5 years (range 5–53). 18 patients (75%) had additional neuropsychiatric and systemic manifestations. Causative mutations in up to 10 genes were found in 16 of the 22 pedigrees (73%). The genes were traditionally linked to hereditary spastic paraplegia, hereditary cerebellar ataxia, and other neurogenetic diseases including autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum. The authors note marked genetic diversity but restricted functional themes among the causative genes, suggesting common pathogenic mechanisms to which the corticospinal tract and cerebellar circuits may be especially vulnerable.
An earlier electrophysiological study from 1977 examined 10 patients from three families with uncomplicated familial spastic paraplegia, aged 4 to 41 years. Motor and sensory conduction values all fell within the control range. The authors contrast these findings with Friedreich's ataxia and other spinocerebellar degenerations where peripheral nerve abnormalities are present.
A 2005 report describes hereditary spastic paraplegia with thin corpus callosum and childhood onset in two patients, noting that HSPs are subdivided into pure and complicated forms depending on associated neurologic abnormalities, with autosomal dominant, recessive, and X-linked forms defined.
No drug treatment, clinical trial, or intervention of any kind is mentioned in any of these abstracts. What remains missing for spastic paraplegia 91 specifically is any study that isolates this single genetic form, any prospective natural history data, any biomarker development, and any funding for a trial designed to test a repurposed drug in a genetically defined patient subgroup.
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 Neurology Neurosurgery & Psychiatry · 1977 · 43 citations · open access
Electrophysiological studies in familial spastic paraplegia.
AbstractMotor and sensory conduction studies have been performed in 10 patients from three families with uncomplicated familial spastic paraplegia whose ages ranged from 4 to 41 years. In all cases the values fell within the control range. The findings may be contrasted with those in Friedreich's ataxia and some other spinocerebellar degenerations in which peripheral nerve abnormalities are present.
Frontiers in Neurology · 2022 · 4 citations · open access
Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement
AbstractHereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5-53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable.
Fortschritte der Neurologie · Psychiatrie · 1991 · 4 citations
Familiäre spastische Spinalparalyse - Klinisches Spektrum und differentialdiagnostische Erwägungen
AbstractThe familial spastic paraplegia is a rare disorder of the cerebral nervous system characterized by a slowly progressive spasticity of the lower limbs with early or late onset. There are pure and complicated forms. The disease is inherited by an autosomal dominant mode and a recessive one. In this study 6 patients out of 5 families are presented. The clinical variety, genetic aspects, electrophysiological results and differential diagnosis are discussed.
AbstractDr Harding has provided an excellent clinically oriented approach to the diagnosis and management of hereditary ataxias and spastic paraplegias. Chapter 1 includes a historical perspective and delineates problems of classification of these disorders. The classification system presented is based on an extensive review of the literature and personal experience with over 20 families. Congenital cerebellar ataxias of unknown cause are discussed in chapter 2. Chapter 3 focuses on ataxic disorders associated with known metabolic defects, while chapter 4 reviews those ataxias associated with defective DNA repair. Early-onset ataxic disorders (onset before age 20 years) are covered in chapters 5 through 9, with chapter 5 devoted entirely to Friedreich's ataxia. Chapters 10 and 11 present the autosomal dominant and idiopathic varieties of late-onset cerebellar ataxias. The hereditary spastic paraplegias. The hereditary spastic paraplegias are reviewed in chapters 12 and 13. Chapter 14 is concerned with the differential diagnosis and evaluation of these ataxic and paraplegic disorders at various ages. The book concludes with a discussion of genetic counseling.
Table_1_Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.XLS
Abstract<p>Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5–53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable.</p>
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.
Data_Sheet_1_Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.PDF
Abstract<p>Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders clinically characterized by progressive lower-limb spasticity. Cerebellar ataxia commonly co-occurs with complicated HSPs. HSP with concurrent cerebellar ataxia has significant clinical and genetic overlaps with hereditary cerebellar ataxia (HCA) and other inherited neurological diseases, adding to the challenge of planning genetic testing for the disease. In this study, we characterized clinical features of a cohort of 24 patients (male/female: 15/9) from 22 families who presented spastic paraparesis combined with cerebellar involvement, with a median disease onset age 20.5 (range 5–53) years. Aside from the core phenotype, 18 (75%) patients had additional neuropsychiatric and systemic manifestations. A stepwise genetic testing strategy stratified by mode of inheritance, distinct neuroimaging features (e.g., thin corpus callosum), population-specific prevalence and whole-exome sequencing was utilized to investigate the genetic etiology. Causative mutations in up to 10 genes traditionally related to HSP, HCA and other neurogenetic diseases (autosomal recessive spastic ataxia of Charlevoix-Saguenay, neurodegeneration with brain iron accumulation, and progressive encephalopathy with brain atrophy and thin corpus callosum) were detected in 16 (73%) of the 22 pedigrees. Our study revealed the genetic complexity of HSP combined with cerebellar involvement. In contrast to the marked genetic diversity, the functions of the causative genes are restricted to a limited number of physiological themes. The functional overlap might reflect common underlying pathogenic mechanisms, to which the corticospinal tract and cerebellar neuron circuits may be especially vulnerable.</p>
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.
