DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary spastic paraplegia 2 — 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 moduleHereditary spastic paraplegia 2 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 hereditary spastic paraplegia 2 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
spastin (SPAST) — SPAST 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PEK · 4.2 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary spastic paraplegia 2 is not mentioned in any of the provided abstracts. The abstracts describe hereditary spastic paraplegia as a group of neurodegenerative conditions defined by progressive lower limb spastic paralysis due to corticospinal tract degeneration, with at least 20 genes involved and extreme genetic heterogeneity. One abstract from 2006 reports a new locus on chromosome 8p12-p11.21 for autosomal recessive HSP with thin corpus callosum and epilepsy, identified in two consanguineous families with a combined lod score of 7.077 at marker D8S505; candidate genes in that interval are neuregulin and KIF13B. Another abstract notes that in Caucasian populations, heterozygous Spastin mutations (SPG4) account for the majority of HSP patients, with onset typically in the third or fourth decade, while childhood onset is more common in SPG3a or complicated forms like SPG11.
Balance impairments are common and debilitating in HSP, frequently causing falls and fall-related injuries, according to a 2017 review. That review recommends multidisciplinary treatment tailored to identified underlying mechanisms, based on scientific evidence when available and otherwise on practice-based evidence and clinical experience. An earlier 1988 report describes six families with 26 affected members, all initially referred as children with slowly progressive paraplegia, slightly delayed motor milestones, normal intellect, and no perinatal cerebral event; treatment consisted of tendon lengthenings when necessary, and the authors emphasise that recognition through careful patient and family history is key to management.
No drug treatment, repurposed or otherwise, is tested or recommended in any of these abstracts. What is missing for any potential therapy in hereditary spastic paraplegia 2 specifically is any mention of the condition at all in the provided literature, let alone clinical trial data, patient stratification, or funding for a targeted study.
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 Medical Genetics · 2003 · 168 citations · open access
Science in motion: common molecular pathological themes emerge in the hereditary spastic paraplegias: Table 1
AbstractThe hereditary spastic paraplegias are a group of neurodegenerative conditions that all share the principal clinical feature of progressive lower limb spastic paralysis, caused by either failure of development or progressive degeneration of the corticospinal tract. The conditions are characterised by extreme genetic heterogeneity, with at least 20 genes involved. Until recently, no functional overlap was apparent in the associated molecular pathological mechanisms. However, with recent progress in hereditary spastic paraplegia gene identification, common pathological themes are now emerging.
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.
Journal of Rehabilitation Medicine · 2017 · 22 citations · open access
Pathophysiology, diagnostic work-up and management of balance impairments and falls in patients with hereditary spastic paraplegia
AbstractINTRODUCTION: Balance impairments are common in patients with hereditary spastic paraplegia and are among the most debilitating symptoms, as they frequently result in falls and fall-related injuries. Several features of hereditary spastic paraplegia contribute to balance impairments and multiple treatment options exist. However, an overview of these underlying mechanisms and their treatment is currently lacking. METHODS: This paper reviews the pathophysiology, diagnostic workup, and management of balance impairments in hereditary spastic paraplegia. Recommendations are based on scientific evidence, when available, and otherwise reflect practice-based evidence supported by clinical experience. CONCLUSION: Through diligent history-taking and clinical examination, followed by multidisciplinary treatment tailored to the identified underlying mechanisms, balance capacities can be improved in patients with hereditary spastic paraplegia and at least a proportion of falls can be prevented.
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.
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.
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.
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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