SynthesisOrphanet journal of rare diseases2023
A systematic review of clinical effectiveness and safety for historical and current treatment options for metachromatic leukodystrophy in children, including atidarsagene autotemcel.
Synthesis in Orphanet journal of rare diseases, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.
- Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States.Cytotherapy · 2024Guideline
- Newborn Screening for Metachromatic Leukodystrophy: A Systematic Literature Review.International journal of neonatal screening · 2025Review
- Stem cell and gene therapies for leukodystrophies.Molecular therapy. Methods & clinical development · 2025Review
- Subspecialty neurology genetic counselors-A cost effective solution to substantial time costs associated with genomic testing in the neurology clinic.Journal of genetic counseling · 2025Article
- A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2024.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Clinical and Radiological Profile of Nine Patients with Metachromatic Leukodystrophy.Molecular syndromology · 2025Article
- Metachromatic Leukodystrophy Presenting with Multiple Cranial Nerve and Lumbosacral Nerve Root Enhancement Without White Matter Changes.Neurology international · 2025Article
- Current Advances and Challenges in Gene Therapies for Neurologic Disorders: A Review for the Clinician.Neurology. Genetics · 2025Review
- 'Lenmeldy (OTL-200) in MLD: FDA's validation of advanced therapy'.Annals of medicine and surgery (2012) · 2024Article
- Hematopoietic Stem Cell Transplantation for Storage Disorders: Present Status.Indian journal of pediatrics · 2024Review
- Gene therapy for the leukodystrophies: From preclinical animal studies to clinical trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo understand the benefit-risk profile for historical and current treatments for MLD.
methodsA systematic review was conducted on the effectiveness, safety, and costs of MLD treatments: allogeneic haematopoietic stem cell transplantation (HSCT) and atidarsagene autotemcel (arsa-cel) according to best practice.
resultsA total of 6940 titles and abstracts were retrieved from the literature searches and 26 from other sources. From these, 35 manuscripts reporting on a total of 12 studies were selected for inclusion in the review. There were no controlled multi-armed trials. However, we provide observations comparing two interventional therapies (alloHSCT and arsa-cel) and each of these to standard/supportive care (natural history). There were no benefits for survival, gross motor function and cognitive function for LI patients receiving alloHSCT, as patients experienced disease progression similar to LI natural history. For juvenile patients receiving alloHSCT, no differences in survival were observed versus natural history, however stabilisation of cognitive and motor function were reported for some patients (particularly for pre- or minimally-symptomatic LJ patients), while others experienced disease progression. Furthermore, alloHSCT was associated with severe complications such as treatment-related mortality, graft versus host disease, and re-transplantation in both LI and EJ treated patients. Most LI and EJ patients treated with arsa-cel appeared to have normal development, preservation, or slower progression of gross motor function and cognitive function, in contrast to the rapid decline observed in natural history patients. A survival benefit for arsa-cel versus natural history and versus alloHSCT was observed in LI patients.LI and EJ patients treated with arsa-cel had better gross motor function and cognitive function compared to alloHSCT, which had limited effect on motor and cognitive decline. No data has been reported for arsa-cel treatment of LJ patients.
conclusionsOverall, this systematic review indicates that compared to NHx and HSCT, treatment with arsa-cel results in clinically relevant benefits in LI and EJ MLD patients by preserving cognitive function and motor development in most patients, and increased survival for LI patients. Nevertheless, further research is required to confirm these findings, given they are based on results from non-RCT studies.
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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.