ReviewHuman molecular genetics2011
Combination therapies for lysosomal storage disease: is the whole greater than the sum of its parts?
Review in Human molecular genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 63 citations in OpenAlex.
- Bringing the rare into sight: applications of haploidentical stem cell transplantation in the treatment of rare diseases.Bone marrow transplantation · 2026Review
- Cellular trafficking and fate mapping of cells within the nervous system after in utero hematopoietic cell transplantation.Communications biology · 2024Article
- Life-Limiting Peripheral Organ Dysfunction in Feline Sandhoff Disease Emerges after Effective CNS Gene Therapy.Annals of neurology · 2023Article
- Preclinical studies in Krabbe disease: A model for the investigation of novel combination therapies for lysosomal storage diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- A kaleidoscopic view of extracellular vesicles in lysosomal storage disorders.Extracellular vesicles and circulating nucleic acids · 2022Review
- Enhanced Efficacy and Increased Long-Term Toxicity of CNS-Directed, AAV-Based Combination Therapy for Krabbe Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Stem Cell Applications in Lysosomal Storage Disorders: Progress and Ongoing Challenges.Advances in experimental medicine and biology · 2021Article
- The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Altered Gene Expression in Prefrontal Cortex of a Fabry Disease Mouse Model.Frontiers in molecular neuroscience · 2018Article
- Inclusion bodies of aggregated hemosiderins in liver macrophages.Medical molecular morphology · 2017Article
- A Prospective Treatment Option for Lysosomal Storage Diseases: CRISPR/Cas9 Gene Editing Technology for Mutation Correction in Induced Pluripotent Stem Cells.Diseases (Basel, Switzerland) · 2017Review
- Signatures of Altered Gene Expression in Dorsal Root Ganglia of a Fabry Disease Mouse Model.Frontiers in molecular neuroscience · 2017Article
- Low-dose Gene Therapy Reduces the Frequency of Enzyme Replacement Therapy in a Mouse Model of Lysosomal Storage Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones.Journal of neuroscience research · 2016Review
- Molecular Mechanisms of Disease Pathogenesis Differ in Krabbe Disease Variants.Traffic (Copenhagen, Denmark) · 2016Article
- Combination Therapies for Lysosomal Storage Diseases: A Complex Answer to a Simple Problem.Pediatric endocrinology reviews : PER · 2016Review
- Anti-inflammatory Therapy With Simvastatin Improves Neuroinflammation and CNS Function in a Mouse Model of Metachromatic Leukodystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Neuroinflammatory paradigms in lysosomal storage diseases.Frontiers in neuroscience · 2015Review
- Gene therapy for the neurological manifestations in lysosomal storage disorders.Journal of lipid research · 2014Review
- Factors and processes modulating phenotypes in neuronopathic lysosomal storage diseases.Metabolic brain disease · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Lysosomal storage diseases (LSDs), as a group, are among the most common inherited diseases affecting children. The primary defect is typically a genetic deficiency of one of the lysosomal enzymes, often causing accumulation of undegraded substrates within the lysosome. This accumulation causes numerous secondary effects that contribute to the disease phenotype. Viral-mediated gene therapy (GT) can supply a persistent source of the deficient enzyme. However, with some notable exceptions, GT has been only modestly successful as a single approach. Recently, various therapies have been combined in order to more effectively target the diverse pathogenic mechanisms at work in LSDs. One strategy that has shown promise involves providing a persistent source of the deficient enzyme (GT, stem cell transplantation) while targeting a secondary consequence of disease with a more transient approach (substrate reduction, anti-inflammatories, pharmacological mimetic, etc.). This general strategy has resulted in both additive and synergistic effects. Interestingly, some therapeutic approaches by themselves provide essentially no clinical benefit but contribute greatly to the overall efficacy when used in combination with other treatments. Unfortunately, no therapeutic combination is universally effective. This adds to the difficulty in predicting and identifying combinations that will be most effective for individual LSDs. A better understanding of both pathogenic and therapeutic mechanisms is necessary in order to identify potentially successful combinations. While a single treatment would be ideal, the complex nature of these diseases may unavoidably limit the efficacy of single therapies. In order to more successfully treat LSDs, a shift in focus towards a combination therapy may be necessary.
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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.