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Journal of Neurology, Neurosurgery, and... Dec 2022Adeno-associated virus (AAV) gene therapies are generating much excitement in the rare disease field, particularly for previously untreatable neurological conditions.... (Review)
Review
Adeno-associated virus (AAV) gene therapies are generating much excitement in the rare disease field, particularly for previously untreatable neurological conditions. Efficacy has been claimed for several gene therapy products and the number of trials is rapidly increasing. However, reports of severe treatment-related adverse reactions are emerging, including death. There is still insufficient knowledge about their aetiology, prevention and treatment. We therefore undertook to systematically review publicly available data on AAV gene therapies in order to collate existing information on both safety and efficacy. Here, we review emerging efficacy reports of these novel therapies, many of which show promise. We also collate an increasing number of adverse reactions. Overwhelmingly, these results make a case for unified reporting of adverse events. This is likely to be critical for improving the safety of these promising treatments.
Topics: Humans; Dependovirus; Genetic Therapy; Neurology
PubMed: 36190933
DOI: 10.1136/jnnp-2022-329431 -
Gene Therapy Apr 2023Gene therapy has seen a transformation from a proof-of-concept approach to a clinical reality over the past several decades, with adeno-associated virus (AAV)-mediated... (Meta-Analysis)
Meta-Analysis
Gene therapy has seen a transformation from a proof-of-concept approach to a clinical reality over the past several decades, with adeno-associated virus (AAV)-mediated gene therapy emerging as the leading platform for in vivo gene transfer. A systematic review of AAV-based gene therapies in clinical development was conducted herein to determine why only a handful of AAV-based gene therapy products have achieved market approval. The indication to be treated, route of administration and vector design were investigated as critical factors and assessed for their impact on clinical safety and efficacy. A shift in recent years towards high-dose systemic administration for the treatment of metabolic, neurological and haematological diseases was identified, with intravenous administration demonstrating the highest efficacy and safety risks in clinical trials. Recent years have seen a decline in favour of traditional AAV serotypes and promoters, accompanied by an increase in favour and higher clinical success rate for novel capsids and tissue-specific promoters. Furthermore, a meta-analysis was performed to identify factors that may inhibit the translation of therapeutic efficacy from preclinical large animal studies to first-in-human clinical trials and a detrimental effect on clinical efficacy was associated with alterations to administration routes.
Topics: Animals; Humans; Dependovirus; Genetic Therapy; Capsid; Genetic Vectors
PubMed: 36089633
DOI: 10.1038/s41434-022-00363-0 -
Asia-Pacific Journal of Ophthalmology...Genetic eye diseases, representing a wide spectrum of simple and complex conditions, are one of the leading causes of visual loss in children and working adults, and...
Genetic eye diseases, representing a wide spectrum of simple and complex conditions, are one of the leading causes of visual loss in children and working adults, and progress in the field has led to changes in disease investigation, diagnosis, and management. The past 15 years have seen the emergence of novel therapies for these previously untreatable conditions to the extent that we now have a licensed therapy for one form of genetic eye disease and many more in clinical trial. This is a systematic review of published and ongoing clinical trials of gene therapies for monogenic eye diseases. Databases of clinical trials and the published literature were searched for interventional studies of gene therapies for eye diseases. Standard methodological procedures were used to assess the relevance of search results. A total of 59 registered clinical trials are referenced, showing the significant level of interest in the potential for translation of these therapies from bench to bedside. The breadth of therapy design is encouraging, providing multiple possible therapeutic mechanisms. Some fundamental questions regarding gene therapy for genetic eye diseases remain, such as optimal dosing, the relative benefits of adeno-associated virus (AAV)-packaging and the potential for a significant inflammatory response to the therapy itself. As a result, despite the promise of the eye as a target, it has proven difficult to deliver clinically effective gene therapies to the eye. Despite setbacks, the licensing of Luxturna (voretigene neparvovec, Novartis) for the treatment of RPE65-mediated Leber congenital amaurosis (LCA) is a major advance in efforts to treat these rare, but devastating, causes of visual loss.
Topics: Adult; Child; Dependovirus; Eye Diseases; Genetic Therapy; Genetic Vectors; Humans; Leber Congenital Amaurosis; Mutation; cis-trans-Isomerases
PubMed: 36041151
DOI: 10.1097/APO.0000000000000545 -
Journal of Emergency Nursing Jul 2022Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19....
INTRODUCTION
Immunoglobulin A vasculitis is historically more commonly found in children after certain viral infections such as Epstein-Barr, varicella virus, and parvovirus B19. COVID-19 has not been formally established in literature as a trigger for immunoglobulin A vasculitis. However, a main pathogenetic mechanism of COVID-19 is vascular damage, which makes it likely that vasculitis associated with COVID-19 (ie, COVID-19-mediated immunoglobulin A vasculitis) could be biologically plausible, with serious implications, especially for adults. The purpose of this review is to assist emergency nurses in gaining knowledge on the pathophysiology, symptoms, and treatment of COVID-19-mediated immunoglobulin A vasculitis.
METHODS
A systematic search for case reports of COVID-19-associated immunoglobulin A vasculitis was conducted in the PubMed and Scopus electronic databases. The search terms used were COVID-19, coronavirus 2019, SARS COVID-19, and IgA vasculitis, case reports. The following were the inclusion criteria: publication dates between December 1, 2019, and December 1, 2021; full-text article, clinical case studies, and letters to the editor available electronically in English. The following were exclusion criteria: a summary of reports and newspaper publications.
RESULTS
Only 13 clinical cases met the inclusion criteria. The median age of patients described in the case reports were 38.1 years. Of them, 3 children were less than 5 years old. Twelve patients were male. In 7 of 13 cases of immunoglobulin A vasculitis, renal involvement was found.
DISCUSSION
The analysis of published clinical cases showed that COVID-19-associated immunoglobulin A vasculitis affected mostly adults and was characterized by a more severe course because of renal involvement. COVID-19 may be a possible trigger for immunoglobulin A-related disorders. More research is needed to better understand the relationship between immunoglobulin A vasculitis and COVID-19.
Topics: Adult; COVID-19; Child; Child, Preschool; Female; Humans; IgA Vasculitis; Immunoglobulin A; Male; Vasculitis
PubMed: 35691763
DOI: 10.1016/j.jen.2022.05.002 -
Translational Research : the Journal of... Oct 2022Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of... (Review)
Review
Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of multiple gene therapies to treat human diseases. The intranasal route of vector application in gene therapy offers several advantages over traditional ways of administration. In addition to targeting local tissue like the olfactory epithelium, it provides minimally invasive access to various organ systems, including the central nervous system and the respiratory tract. Through a systematic literature review, a total of 53 articles that investigated the intranasal application of AAVs were identified, included, and summarized in this manuscript. Within these studies, AAV-based gene therapy was mainly investigated for its application in various infectious, pulmonary, or neurologic and/or psychiatric diseases. This review gives a comprehensive overview of the current technological state of the art regarding the intranasal application of AAVs for gene transfer and discusses remaining hurdles, which still have to be resolved before this approach can effectively be implemented in the routine clinical setting.
Topics: Administration, Intranasal; Dependovirus; Gene Transfer Techniques; Genetic Therapy; Genetic Vectors; Humans
PubMed: 35597541
DOI: 10.1016/j.trsl.2022.05.002 -
Journal of Perinatal Medicine Sep 2022To identify the prevalence of viral congenital infections in newborns classified as premature, low-birthweight, small for gestational age or intrauterine growth...
Diagnosis of congenital infections in premature, low-birthweight newborns with intrauterine growth restriction caused by cytomegalovirus (CMV), herpes simplex virus (HSV), Parvo-B 19, and Zika virus: a systematic review.
OBJECTIVES
To identify the prevalence of viral congenital infections in newborns classified as premature, low-birthweight, small for gestational age or intrauterine growth restriction.
METHODS
The definition considered for selecting papers were: P as newborns younger than 28 days; V as low-birthweight, prematurity and intrauterine growth restriction; O as frequency of congenital infections with Cytomegalovirus, Parvovirus B19, Herpes Simplex, and Zika virus. The research was performed using EMBASE, LILACS, SCOPUS and MEDLINE databases, with no limitations on date and language.
RESULTS
Eight studies were included. Manuscripts including Herpes Simplex, Zika virus or Parvovirus B19 did not fulfill the defined criteria. A wide variation in the frequency of CMV congenital infection (0-4.8%) was found, which might be attributed to regional and methodological differences between investigations.
CONCLUSIONS
Newborn characteristics associated with CMV congenital infections may direct investigations towards these patients with a higher probability of infection. However, as data are controversial, studies concerning screening of infection are important to define recommendations of diagnosis.
Topics: Birth Weight; Cytomegalovirus; Cytomegalovirus Infections; Female; Fetal Growth Retardation; Herpes Simplex; Humans; Infant, Newborn; Infant, Newborn, Diseases; Parvovirus B19, Human; Pregnancy; Pregnancy Complications, Infectious; Simplexvirus; Zika Virus; Zika Virus Infection
PubMed: 35427445
DOI: 10.1515/jpm-2021-0244 -
Frontiers in Pharmacology 2021Viruses cause various human diseases, some of which become pandemic outbreaks. This study synthesized evidence on antiviral medicinal plants in Africa which could... (Review)
Review
Viruses cause various human diseases, some of which become pandemic outbreaks. This study synthesized evidence on antiviral medicinal plants in Africa which could potentially be further studied for viral infections including Coronavirus disease 2019 (COVID-19) treatment. PUBMED, CINAHIL, Scopus, Google Scholar, and Google databases were searched through keywords; antiviral, plant, herb, and Africa were combined using "AND" and "OR". studies, studies, or clinical trials on botanical medicine used for the treatment of viruses in Africa were included. Thirty-six studies were included in the evidence synthesis. Three hundred and twenty-eight plants were screened for antiviral activities of which 127 showed noteworthy activities against 25 viral species. These, were Poliovirus (42 plants), HSV (34 plants), Coxsackievirus (16 plants), Rhinovirus (14plants), Influenza (12 plants), Astrovirus (11 plants), SARS-CoV-2 (10 plants), HIV (10 plants), Echovirus (8 plants), Parvovirus (6 plants), Semiliki forest virus (5 plants), Measles virus (5 plants), Hepatitis virus (3 plants), Canine distemper virus (3 plants), Zika virus (2 plants), Vesicular stomatitis virus T2 (2 plants). Feline herpesvirus (FHV-1), Enterovirus, Dengue virus, Ebola virus, Chikungunya virus, Yellow fever virus, Respiratory syncytial virus, Rift Valley fever virus, Human cytomegalovirus each showed sensitivities to one plant. The current study provided a list of African medicinal plants which demonstrated antiviral activities and could potentially be candidates for COVID-19 treatment. However, all studies were preliminary and screening. Further are required for plant-based management of viral diseases.
PubMed: 35002686
DOI: 10.3389/fphar.2021.682794 -
Asian Journal of Transfusion Science 2021Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not... (Review)
Review
BACKGROUND
Human parvovirus B19 (B19V) is one of the blood-borne viruses. The virus can be transmitted to susceptible individuals by blood or blood products. The virus is not associated with significant disease in general population, while people with underlying problems such as immunodeficiency can cause anemia and arthritis. The current systematic review and meta-analysis aimed to estimate the overall prevalence of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies in blood donors worldwide.
METHODS
A systematic search was carried out in online databases for relevant studies from inception until March 30, 2019. Study selection was performed based on predesigned eligibility criteria. The proportion of B19V DNA, anti-B19V IgG, and anti-B19V IgM antibodies were pooled using the inverse variance method. All statistical analyses were performed using the R version 3.5.3, package "meta."
RESULTS
According to the random-effects model, the pool prevalence of B19V DNA, anti-B19V IgM, and anti-B19V IgG among blood donors was calculated to be 0.4% (95% confidence interval [CI] =0.3%-0.6%), 2.2% (95% CI = 1.3%-3.7%), and 50.1% (95% CI = 43.1%-57.1%), respectively.
CONCLUSION
For the transmission of B19V through blood, the presence of the virus genome is required, and the present study showed that the prevalence of the virus genome in blood donors is <1%. Therefore, there is no need to screen donated blood for B19V infection.
PubMed: 34908757
DOI: 10.4103/ajts.ajts_185_20 -
Microbial Pathogenesis Jan 2022The potential association between Parvovirus B19 and heart disease has been controversial. The aim of the present study was to report the prevalence of B19 in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The potential association between Parvovirus B19 and heart disease has been controversial. The aim of the present study was to report the prevalence of B19 in myocarditis and dilated cardiomyopathy (DCM) as well as measure the statistical association between them.
METHODS
Our systematic search was carried out to retrieve published articles between January 2000 and March 2021 using three major databases: PubMed, Scopus, and Web of Science, as well as the Google Scholar search engine. The overall prevalence of HAV, pooled odds ratio, and heterogeneity were estimated by comprehensive meta-analysis (V2.2, Biostat) software.
RESULTS
The overall prevalence results in myocarditis and DCM were 23.7% (95% CI: 18.7%-29.5%) and 34.1% (95% CI: 23.8%-46.1%) respectively; in addition, the overall OR for B19 and myocarditis was 4.317 (95% CI, 1.831-10.180) versus 1.163 (95% CI: 0.706-1.916) for B19 and DCM.
CONCLUSION
Our findings have shown a significant association between Parvovirus B19 and myocarditis with a high prevalence. In the case of DCM, no significant association was found while the prevalence of the virus was relatively high.
Topics: Cardiomyopathy, Dilated; Humans; Myocarditis; Parvoviridae Infections; Parvovirus B19, Human; Prevalence
PubMed: 34563612
DOI: 10.1016/j.micpath.2021.105207 -
Journal of Tropical Pediatrics Aug 2021An increasing number of reports have described human parvovirus B19 infection in association with a variety of neurological manifestations, especially in children. This...
An increasing number of reports have described human parvovirus B19 infection in association with a variety of neurological manifestations, especially in children. This study assessed the clinical and laboratory outcomes found in a case series of immunocompetent children who tested positive for parvovirus B19 by qualitative polymerase chain reaction assays of cerebrospinal fluid, in a tertiary referral center in the western Brazilian Amazon. We screened 178 children with clinically diagnosed central nervous system infections (meningoencephalitis). Of these, five (2.8%) were positive for parvovirus B19. A literature review also presented herein identified a further 50 cases of parvovirus B19 with neurological manifestations. Thus, even if the classic signs of parvovirus B19 infection are absent, such as the well-known rash, children with signs of neurological infection should also be evaluated for parvovirus B19 infection.
Topics: Child; Erythema Infectiosum; Humans; Nervous System Diseases; Parvoviridae Infections; Parvovirus B19, Human; Polymerase Chain Reaction
PubMed: 34545404
DOI: 10.1093/tropej/fmab078