ArticleNature medicine2024
AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient.
Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06069687 (A Phase 1 Open-label Intrathecal Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50), which is not on this map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1 Open-label Intrathecal Administration of MELPIDA to Determine the Safety and Efficacy for Patients With Spastic Paraplegia Type 50 (SPG50) Caused by a Mutation in the AP4M1 Gene
Who cites it
25 citing papers in PubMed.
- Trial
- Individualized antisense oligonucleotide treatment eligibility of patients living with neurodevelopmental diseases.Cell reports. Medicine · 2026Review
- Digital Motor Outcomes Capture Upper Limb and Mild Stage Impairment in Hereditary Spastic Paraplegia.Neurology and therapy · 2026Article
- Review
- AAV-mediated gene therapy in a model of SLC13A5 citrate transporter disorder rescues epileptic and metabolic phenotypes.The Journal of clinical investigation · 2026Article
- Diagnostic Utility of the ATG9A Ratio in AP-4-Associated Hereditary Spastic Paraplegia.Annals of clinical and translational neurology · 2026Article
- A blueprint to accelerate rare pediatric gene therapy approvals.Nature medicine · 2026Article
- Designs of the clinical trials aiming at evaluating cell and gene therapy products: A critical appraisal from a literature review.Molecular therapy. Advances · 2026Review
- Review
- Splice effect of a synonymous variant inHuman mutation · 2026Article
- A NovelIranian journal of medical sciences · 2026Article
- Hereditary spastic paraplegia: from decades of therapy to future innovations.Therapeutic advances in neurological disorders · 2026Review
- A Case of Hereditary Spastic Paraplegia Type 50 With a Novel AP4M1 Variant and a Brief Review of the Literature.Clinical case reports · 2025Article
- Tailored antisense oligonucleotides for ultrarare CNS diseases: An experience-based best practice framework for individual patient evaluation.Molecular therapy. Nucleic acids · 2025Review
- Fetal and Perinatal Brain MRI Findings in Adaptor Protein Complex 4-Associated Hereditary Spastic Paraplegia.Annals of the Child Neurology Society · 2025Article
- A father's crusade in rare disease drug development: a case study of Elpida therapeutics and Melpida.Orphanet journal of rare diseases · 2025Article
- Natural History of NAA15 -Related Neurodevelopmental Disorder Through Adolescence.American journal of medical genetics. Part A · 2025Article
- From precision interventions to precision health.Nature communications · 2025Review
- International Precision Child Health Partnership (IPCHiP): an initiative to accelerate discovery and improve outcomes in rare pediatric disease.NPJ genomic medicine · 2025Review
- Gene-replacement therapy in neurodevelopmental disorders: progress and challenges.The Journal of clinical investigation · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
There are more than 10,000 individual rare diseases and most are without therapy. Personalized genetic therapy represents one promising approach for their treatment. We present a road map for individualized treatment of an ultra-rare disease by establishing a gene replacement therapy developed for a single patient with hereditary spastic paraplegia type 50 (SPG50). Through a multicenter collaboration, an adeno-associated virus-based gene therapy product carrying the AP4M1 gene was created and successfully administered intrathecally to a 4-year-old patient within 3 years of diagnosis as part of a single-patient phase 1 trial. Primary endpoints were safety and tolerability, and secondary endpoints evaluated efficacy. At 12 months after dosing, the therapy was well tolerated. No serious adverse events were observed, with minor events, including transient neutropenia and Clostridioides difficile gastroenteritis, experienced but resolved. Preliminary efficacy measures suggest a stabilization of the disease course. Longer follow-up is needed to confirm the safety and provide additional insights on the efficacy of the therapy. Overall, this report supports the safety of gene therapy for SPG50 and provides insights into precision therapy development for rare diseases. Clinical trial registration: NCT06069687 .
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.