Gene therapy strategies in the treatment of hypertrophic cardiomyopathy
Standard
Gene therapy strategies in the treatment of hypertrophic cardiomyopathy. / Prondzynski, Maksymilian; Mearini, Giulia; Carrier, Lucie.
In: PFLUG ARCH EUR J PHY, Vol. 471, No. 5, 05.2019, p. 807-815.Research output: SCORING: Contribution to journal › SCORING: Review article › Research
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Gene therapy strategies in the treatment of hypertrophic cardiomyopathy
AU - Prondzynski, Maksymilian
AU - Mearini, Giulia
AU - Carrier, Lucie
PY - 2019/5
Y1 - 2019/5
N2 - Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease with an estimated prevalence of 1:200 caused by mutations in sarcomeric proteins. It is associated with hypertrophy of the left ventricle, increased interstitial fibrosis, and diastolic dysfunction for heterozygous mutation carriers. Carriers of double heterozygous, compound heterozygous, and homozygous mutations often display more severe forms of cardiomyopathies, ultimately leading to premature death. So far, there is no curative treatment against HCM, as current therapies are focused on symptoms relief by pharmacological intervention and not on the cause of HCM. In the last decade, several strategies have been developed to remove genetic defects, including genome editing, exon skipping, allele-specific silencing, spliceosome-mediated RNA trans-splicing, and gene replacement. Most of these technologies have already been tested for efficacy and efficiency in animal- or human-induced pluripotent stem cell models of HCM with promising results. We will summarize recent technological advances and their implication as gene therapy options in HCM with a special focus on treating MYBPC3 mutations and its potential for being a successful bench to bedside example.
AB - Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease with an estimated prevalence of 1:200 caused by mutations in sarcomeric proteins. It is associated with hypertrophy of the left ventricle, increased interstitial fibrosis, and diastolic dysfunction for heterozygous mutation carriers. Carriers of double heterozygous, compound heterozygous, and homozygous mutations often display more severe forms of cardiomyopathies, ultimately leading to premature death. So far, there is no curative treatment against HCM, as current therapies are focused on symptoms relief by pharmacological intervention and not on the cause of HCM. In the last decade, several strategies have been developed to remove genetic defects, including genome editing, exon skipping, allele-specific silencing, spliceosome-mediated RNA trans-splicing, and gene replacement. Most of these technologies have already been tested for efficacy and efficiency in animal- or human-induced pluripotent stem cell models of HCM with promising results. We will summarize recent technological advances and their implication as gene therapy options in HCM with a special focus on treating MYBPC3 mutations and its potential for being a successful bench to bedside example.
KW - Journal Article
KW - Review
U2 - 10.1007/s00424-018-2173-5
DO - 10.1007/s00424-018-2173-5
M3 - SCORING: Review article
C2 - 29971600
VL - 471
SP - 807
EP - 815
JO - PFLUG ARCH EUR J PHY
JF - PFLUG ARCH EUR J PHY
SN - 0031-6768
IS - 5
ER -