DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary spastic paraplegia 77 — 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 moduleHereditary spastic paraplegia 77 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 hereditary spastic paraplegia 77 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
phenylalanyl-tRNA synthetase 2, mitochondrial (FARS2) — FARS2 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 fa5drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3CMQ · 2.2 Å · ligand ADENOSINE-5'-[PHENYLALANINYL-PHOSPHATE] (FA5). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary spastic paraplegia 77 is not mentioned in any of the provided abstracts. The abstracts discuss hereditary spastic paraplegia generally and specific subtypes SPG4, SPG3a, SPG7, and SPG11, but no abstract names or describes SPG77. One abstract from 2025 reports a Korean cohort of 69 patients with spastic paraplegia from 54 families, followed over two decades. In that cohort, the median age of symptom onset was 25 years. Spastic gait was universal. Urinary dysfunction occurred in 42 patients (61%). Additional features included peripheral neuropathy in 9 (13%), cognitive impairment in 5 (7%), upper limb weakness in 4 (6%), dysarthria in 4 (6%), dysphagia in 3 (4%), ataxia in 3 (4%), and scoliosis in 1 (3%). Brain MRI showed a thin corpus callosum only in two patients with SPG11; all SPG4 patients had normal brain MRI. Spinal cord atrophy was seen in 16 patients (27%), including 6 with SPG4.
The 2017 abstract describes a single SPG7 patient with an expanded phenotype diagnosed after finding pathogenic variants in SPG7. The 2015 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, and that childhood manifestation is more common in SPG3a or complicated forms like SPG11. The 2005 abstract states that HSPs are rare disorders with spastic gait as the predominant feature, subdivided into pure and complicated forms, and that autosomal dominant, recessive, and X-linked forms exist.
No abstract provides any data on treatment, drug repurposing, or clinical trials for hereditary spastic paraplegia 77 or any other HSP subtype. There is no mention of any drug, therapy, or intervention. The abstracts are purely descriptive of clinical and genetic features. What is missing for SPG77 specifically is any published evidence at all: no case series, no natural history data, no genetic characterisation, no biomarker studies, and no trial design or patient stratification efforts. Without even a single abstract describing SPG77, no conclusions about its phenotype, prevalence, or potential treatments can be drawn.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Case Reports · 2017 · 12 citations · open access
Expanded phenotype in a patient with spastic paraplegia 7
AbstractKey Clinical Message Hereditary spastic paraplegia is a group of clinically and genetically heterogeneous neurodegenerative disorders, often characterized by weakness and spasticity in the lower limbs. In our study, we describe a spastic paraplegia type 7 patient with an expanded phenotype who was diagnosed after the discovery of pathogenic variants in SPG 7 .
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.
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.
