Ability of Adeno-Associated Virus Serotype 8-Mediated Hepatic Expression of Acid α-Glucosidase to Correct the Biochemical and Motor Function Deficits of Presymptomatic and Symptomatic Pompe Mice

2008 ◽  
Vol 19 (6) ◽  
pp. 609-621 ◽  
Author(s):  
Robin J. Ziegler ◽  
Scott D. Bercury ◽  
Jonathan Fidler ◽  
Michael A. Zhao ◽  
Joseph Foley ◽  
...  
Keyword(s):  
Motor Function ◽  
Adeno Associated Virus ◽  
Hepatic Expression ◽  
Virus Serotype

scholarly journals X-linked myotubular myopathy

Neurology ◽  
2019 ◽  
Vol 92 (16) ◽  
pp. e1852-e1867 ◽  
Author(s):  
Mélanie Annoussamy ◽  
Charlotte Lilien ◽  
Teresa Gidaro ◽  
Elena Gargaun ◽  
Virginie Chê ◽  
...  
Keyword(s):  
Natural History ◽  
Motor Function ◽  
Forced Expiratory Volume ◽  
Intermediate Phenotype ◽  
Adeno Associated Virus ◽  
Mild Phenotype ◽  
Myotubular Myopathy ◽  
Virus Serotype ◽  
Ventilation Support ◽  
Function Measure

ObjectivesBecause X-linked myotubular myopathy (XLMTM) is a rare neuromuscular disease caused by mutations in the MTM1 gene with a large phenotypic heterogeneity, to ensure clinical trial readiness, it was mandatory to better quantify disease burden and determine best outcome measures.MethodsWe designed an international prospective and longitudinal natural history study in patients with XLMTM and assessed muscle strength and motor and respiratory functions over the first year of follow-up. The humoral immunity against adeno-associated virus serotype 8 was also monitored.ResultsForty-five male patients aged 3.5 months to 56.8 years were enrolled between May 2014 and May 2017. Thirteen patients had a mild phenotype (no ventilation support), 7 had an intermediate phenotype (ventilation support less than 12 hours a day), and 25 had a severe phenotype (ventilation support 12 or more hours a day). Most strength and motor function assessments could be performed even in very weak patients. Motor Function Measure 32 total score, grip and pinch strengths, and forced vital capacity, forced expiratory volume in the first second of exhalation, and peak cough flow measures discriminated the 3 groups of patients. Disease history revealed motor milestone loss in several patients. Longitudinal data on 37 patients showed that the Motor Function Measure 32 total score significantly decreased by 2%. Of the 38 patients evaluated, anti–adeno-associated virus type 8 neutralizing activity was detected in 26% with 2 patients having an inhibitory titer >1:10.ConclusionsOur data confirm that XLMTM is slowly progressive for male survivors regardless of their phenotype and provide outcome validation and natural history data that can support clinical development in this population.ClinicalTrials.gov identifierNCT02057705.

scholarly journals Epidermal growth factor receptor is a co-receptor for adeno-associated virus serotype 6

2010 ◽  
Vol 16 (6) ◽  
pp. 662-664 ◽  
Author(s):  
Melodie L Weller ◽  
Panomwat Amornphimoltham ◽  
Michael Schmidt ◽  
Paul A Wilson ◽  
J Silvio Gutkind ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Epidermal Growth

Calcium-ion-modulated ceramic hydroxyapatite resin for the scalable purification of recombinant Adeno-Associated Virus serotype 9

2015 ◽  
Vol 990 ◽  
pp. 15-22 ◽  
Author(s):  
Weihong Qu ◽  
Mingxi Wang ◽  
Yaqing Wu ◽  
Yinghui Lv ◽  
Qizhao Wang ◽  
...  
Keyword(s):  
Calcium Ion ◽  
Adeno Associated Virus ◽  
Virus Serotype ◽  
Ceramic Hydroxyapatite

scholarly journals Comparison of the transduction efficiency of tyrosine-mutant adeno-associated virus serotype vectors in kidney

2012 ◽  
Vol 40 (1) ◽  
pp. 53-55 ◽  
Author(s):  
Yan F. Qi ◽  
Qiu H. Li ◽  
Vinayak Shenoy ◽  
Michael Zingler ◽  
Joo Y. Jun ◽  
...  
Keyword(s):  
Transduction Efficiency ◽  
Adeno Associated Virus ◽  
Virus Serotype

scholarly journals Cardiac Overexpression of PDE4B Blunts β-Adrenergic Response and Maladaptive Remodeling in Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (2) ◽  
pp. 161-174 ◽  
Author(s):  
Sarah Karam ◽  
Jean Piero Margaria ◽  
Aurélia Bourcier ◽  
Delphine Mika ◽  
Audrey Varin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mouse ◽  
Adrenergic Receptor ◽  
Systolic Dysfunction ◽  
Fold Increase ◽  
Aortic Constriction ◽  
Adeno Associated Virus ◽  
Transgenic Mouse Line ◽  
Virus Serotype ◽  
Fractional Shortening

Background: The cyclic AMP (adenosine monophosphate; cAMP)-hydrolyzing protein PDE4B (phosphodiesterase 4B) is a key negative regulator of cardiac β-adrenergic receptor stimulation. PDE4B deficiency leads to abnormal Ca 2+ handling and PDE4B is decreased in pressure overload hypertrophy, suggesting that increasing PDE4B in the heart is beneficial in heart failure. Methods: We measured PDE4B expression in human cardiac tissues and developed 2 transgenic mouse lines with cardiomyocyte-specific overexpression of PDE4B and an adeno-associated virus serotype 9 encoding PDE4B. Myocardial structure and function were evaluated by echocardiography, ECG, and in Langendorff-perfused hearts. Also, cAMP and PKA (cAMP dependent protein kinase) activity were monitored by Förster resonance energy transfer, L-type Ca 2+ current by whole-cell patch-clamp, and cardiomyocyte shortening and Ca 2+ transients with an Ionoptix system. Heart failure was induced by 2 weeks infusion of isoproterenol or transverse aortic constriction. Cardiac remodeling was evaluated by serial echocardiography, morphometric analysis, and histology. Results: PDE4B protein was decreased in human failing hearts. The first PDE4B-transgenic mouse line (TG15) had a ≈15-fold increase in cardiac cAMP-PDE activity and a ≈30% decrease in cAMP content and fractional shortening associated with a mild cardiac hypertrophy that resorbed with age. Basal ex vivo myocardial function was unchanged, but β-adrenergic receptor stimulation of cardiac inotropy, cAMP, PKA, L-type Ca 2+ current, Ca 2+ transients, and cell contraction were blunted. Endurance capacity and life expectancy were normal. Moreover, these mice were protected from systolic dysfunction, hypertrophy, lung congestion, and fibrosis induced by chronic isoproterenol treatment. In the second PDE4B-transgenic mouse line (TG50), markedly higher PDE4B overexpression, resulting in a ≈50-fold increase in cardiac cAMP-PDE activity caused a ≈50% decrease in fractional shortening, hypertrophy, dilatation, and premature death. In contrast, mice injected with adeno-associated virus serotype 9 encoding PDE4B (10 12 viral particles/mouse) had a ≈50% increase in cardiac cAMP-PDE activity, which did not modify basal cardiac function but efficiently prevented systolic dysfunction, apoptosis, and fibrosis, while attenuating hypertrophy induced by chronic isoproterenol infusion. Similarly, adeno-associated virus serotype 9 encoding PDE4B slowed contractile deterioration, attenuated hypertrophy and lung congestion, and prevented apoptosis and fibrotic remodeling in transverse aortic constriction. Conclusions: Our results indicate that a moderate increase in PDE4B is cardioprotective and suggest that cardiac gene therapy with PDE4B might constitute a new promising approach to treat heart failure.

Sign in / Sign up

Export Citation Format

Share Document