-
Heart Rhythm Jun 2024Cardiac tachyarrhythmia presents a significant health care challenge, causing notable morbidity and mortality. Conventional treatments have limitations and potential... (Meta-Analysis)
Meta-Analysis
Cardiac tachyarrhythmia presents a significant health care challenge, causing notable morbidity and mortality. Conventional treatments have limitations and potential risks, resulting in an elevated disease burden. Adeno-associated virus (AAV)-mediated gene therapy holds promise as a potential future treatment option. Therefore, we aimed to provide a measured overview of the latest developments in this rapidly growing field. PubMed and Embase databases were searched up to January 2024. Studies that employed AAV as a vector for delivery of therapeutic agents to treat cardiac tachyarrhythmia were included. Of the 26 studies included, 20 published in the last 5 years. There were 22 novel molecular targets identified. More than 80% of the included studies employed small-animal models or used AAV9. In atrial fibrillation preclinical studies, AAV-mediated gene therapy reduced atrial fibrillation inducibility by 81% (odds ratio, 0.19 [0.08-0.45]; P < .01). Similarly, for acquired and inherited ventricular arrhythmia, animal models receiving gene therapy had less inducible ventricular arrhythmia (odds ratio, 0.06 [0.03-0.11]; P < .01). This review highlights the rapid progress of AAV-mediated gene therapy for cardiac tachyarrhythmia. Although these investigations are currently in the early stages of clinical application, they present promising prospects for gene therapy. (PROSPERO registry: CRD42023479448).
Topics: Animals; Humans; Dependovirus; Genetic Therapy; Genetic Vectors; Tachycardia
PubMed: 38336191
DOI: 10.1016/j.hrthm.2024.02.001 -
Human Gene Therapy Feb 2024Clinical trials of adeno-associated virus (AAV)-based gene therapy have made remarkable progress in recent years. We aimed to perform a systematic review and... (Meta-Analysis)
Meta-Analysis
Clinical trials of adeno-associated virus (AAV)-based gene therapy have made remarkable progress in recent years. We aimed to perform a systematic review and meta-analysis of the literature to assess the efficacy and safety of AAV-based gene therapy for hemophilia. We systematically searched the Web of Science, Embase, PubMed, and the Cochrane Database of Systematic Reviews databases, for clinical trials involving patients diagnosed with hemophilia and treated with AAV-mediated gene therapy. Data on the annualized bleeding rate (ABR), annualized infusion rate (AIR), the incidence of treatment-related adverse events (TRAEs), severe adverse events (SAEs), and alanine aminotransferase (ALT) elevation were extracted as our outcomes. A total of 12 articles from 11 clinical trials were selected from 868 articles for meta-analysis. Pooled analyses showed that AAV-based gene therapy in hemophilia patients reduced the number of bleeding events and the number of factor infusion events by an approximate average of 7 per year and 103 per year, respectively. Eighty percent, 18%, and 63% of hemophilia patients had elevated TRAE, SAE, and ALT levels, respectively. Moreover, subgroup analysis found a significant reduction in ABR and AIR 2-3 years after the therapy. Additional findings that were not pooled including coagulation factor activity are presented in the accompanying tables. Our analysis supported the efficacy and safety of AAV-mediated gene therapy for hemophilia, providing evidence for its application as a therapeutic option for widespread clinical use in hemophilia patients in the future.
Topics: Humans; Dependovirus; Genetic Therapy; Genetic Vectors; Hemophilia A; Hemophilia B; Hemorrhage
PubMed: 38185849
DOI: 10.1089/hum.2023.208 -
Translational Vision Science &... Nov 2023This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV). (Meta-Analysis)
Meta-Analysis
PURPOSE
This systematic review evaluates the safety and efficacy of ocular gene therapy using adeno-associated virus (AAV).
METHODS
MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched systematically for controlled or non-controlled interventional gene therapy studies using key words related to retinal diseases, gene therapy, and AAV vectors. The primary outcome measure was safety, based on ocular severe adverse events (SAEs). Secondary outcome measures evaluated efficacy of the therapy based on best corrected visual acuity (BCVA) and improvements in visual sensitivity and systemic involvement following ocular delivery. Pooling was done using a DerSimonian Laird random effects model. Risk of bias was assessed using the Cochrane Risk of Bias Tool, version 1.
RESULTS
Our search identified 3548 records. Of these, 80 publications met eligibility criteria, representing 28 registered clinical trials and 5 postmarket surveillance studies involving AAV gene therapy for Leber congenital amaurosis (LCA), choroideremia, Leber hereditary optic neuropathy (LHON), age-related macular degeneration (AMD), retinitis pigmentosa (RP), X-linked retinoschisis, and achromatopsia. Overall, AAV therapy vectors were associated with a cumulative incidence of at least one SAE of 8% (95% confidence intervals [CIs] of 5% to 12%). SAEs were often associated with the surgical procedure rather than the therapeutic vector itself. Poor or inconsistent reporting of adverse events (AEs) were a limitation for the meta-analysis. The proportion of patients with any improvement in BCVA and visual sensitivity was 41% (95% CIs of 31% to 51%) and 51% (95% CIs of 31% to 70%), respectively. Systemic immune involvement was associated with a cumulative incidence of 31% (95% CI = 21% to 42%).
CONCLUSIONS
AAV gene therapy vectors appear to be safe but the surgical procedure required to deliver them is associated with some risk. The large variability in efficacy can be attributed to the small number of patients treated, the heterogeneity of the population and the variability in dosage, volume, and follow-up.
TRANSLATIONAL RELEVANCE
This systematic review will help to inform and guide future clinical trials.
Topics: Humans; Retinal Degeneration; Dependovirus; Macular Degeneration; Retinitis Pigmentosa; Genetic Therapy
PubMed: 37982768
DOI: 10.1167/tvst.12.11.24 -
Journal of Translational Medicine Oct 2023Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Myalgic encephalitis/chronic fatigue syndrome (ME/CFS) is a long-term disabling illness without a medically explained cause. Recently during COVID-19 pandemic, many studies have confirmed the symptoms similar to ME/CFS in the recovered individuals. To investigate the virus-related etiopathogenesis of ME/CFS, we conducted a systematic assessment of viral infection frequency in ME/CFS patients.
METHODS
We conducted a comprehensive search of PubMed and the Cochrane Library from their inception through December 31, 2022, using selection criteria of viral infection prevalence in ME/CFS patients and controls. Subsequently, we performed a meta-analysis to assess the extent of viral infections' contribution to ME/CFS by comparing the odds ratio between ME/CFS patients and controls (healthy and/or diseased).
RESULTS
Finally, 64 studies met our eligibility criteria regarding 18 species of viruses, including a total of 4971 ME/CFS patients and 9221 control subjects. The participants included healthy subjects and individuals with one of 10 diseases, such as multiple sclerosis or fibromyalgia. Two DNA viruses (human herpes virus (HHV)-7 and parvovirus B19, including their co-infection) and 3 RNA viruses (borna disease virus (BDV), enterovirus and coxsackie B virus) showed odds ratios greater than 2.0 compared with healthy and/or diseased subjects. Specifically, BDV exceeded the cutoff with an odds ratio of ≥ 3.47 (indicating a "moderate association" by Cohen's d test) compared to both healthy and diseased controls.
CONCLUSION
This study comprehensively evaluated the risk of viral infections associated with ME/CFS, and identified BDV. These results provide valuable reference data for future studies investigating the role of viruses in the causation of ME/CFS.
Topics: Humans; Encephalitis; Fatigue Syndrome, Chronic; Fibromyalgia; Virus Diseases
PubMed: 37898798
DOI: 10.1186/s12967-023-04635-0