Abstract
Marfan Syndrome (MFS) is a rare connective tissue disorder, resulting from mutations in the fibrillin-1 gene, characterized by pathologic phenotypes in multiple organs, the most detrimental of which affects the thoracic aorta. Indeed, thoracic aortic aneurysms (TAA), leading to acute dissection and rupture, are today the major cause of morbidity and mortality in adult MFS patients. Therefore, there is a compelling need for novel therapeutic strategies to delay TAA progression and counteract aortic dissection occurrence. Unfortunately, the wide phenotypic variability of MFS patients, together with the lack of a complete genotype-phenotype correlation, have represented until now a barrier hampering the conduction of translational studies aimed to predict disease prognosis and drug discovery. In this review, we will illustrate available therapeutic strategies to improve the health of MFS patients. Starting from gold standard surgical overtures and the description of the main pharmacological approaches, we will comprehensively review the state-of-the-art of in vivo MFS models and discuss recent clinical pharmacogenetic results. Finally, we will focus on induced pluripotent stem cells (iPSC) as a technology that, if integrated with preclinical research and pharmacogenetics, could contribute in determining the best therapeutic approach for each MFS patient on the base of individual differences. Finally, we will suggest the integration of preclinical studies, pharmacogenetics and iPSC technology as the most likely strategy to help solve the composite puzzle of precise medicine in this condition.
| Original language | English |
|---|---|
| Pages (from-to) | 328-335 |
| Number of pages | 8 |
| Journal | Progress in Cardiovascular Diseases |
| Volume | 61 |
| Issue number | 3-4 |
| DOIs | |
| Publication status | Published - Sep 1 2018 |
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Keywords
- FBN1
- iPSC
- Marfan syndrome
- Pharmacogenetics
- TAA
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Precise Therapy for Thoracic Aortic Aneurysm in Marfan Syndrome : A Puzzle Nearing Its Solution. / Rurali, Erica; Perrucci, Gianluca Lorenzo; Pilato, Chiara Assunta; Pini, Alessandro; Gaetano, Raffaella; Nigro, Patrizia; Pompilio, Giulio.
In: Progress in Cardiovascular Diseases, Vol. 61, No. 3-4, 01.09.2018, p. 328-335.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Precise Therapy for Thoracic Aortic Aneurysm in Marfan Syndrome
T2 - A Puzzle Nearing Its Solution
AU - Rurali, Erica
AU - Perrucci, Gianluca Lorenzo
AU - Pilato, Chiara Assunta
AU - Pini, Alessandro
AU - Gaetano, Raffaella
AU - Nigro, Patrizia
AU - Pompilio, Giulio
PY - 2018/9/1
Y1 - 2018/9/1
N2 - Marfan Syndrome (MFS) is a rare connective tissue disorder, resulting from mutations in the fibrillin-1 gene, characterized by pathologic phenotypes in multiple organs, the most detrimental of which affects the thoracic aorta. Indeed, thoracic aortic aneurysms (TAA), leading to acute dissection and rupture, are today the major cause of morbidity and mortality in adult MFS patients. Therefore, there is a compelling need for novel therapeutic strategies to delay TAA progression and counteract aortic dissection occurrence. Unfortunately, the wide phenotypic variability of MFS patients, together with the lack of a complete genotype-phenotype correlation, have represented until now a barrier hampering the conduction of translational studies aimed to predict disease prognosis and drug discovery. In this review, we will illustrate available therapeutic strategies to improve the health of MFS patients. Starting from gold standard surgical overtures and the description of the main pharmacological approaches, we will comprehensively review the state-of-the-art of in vivo MFS models and discuss recent clinical pharmacogenetic results. Finally, we will focus on induced pluripotent stem cells (iPSC) as a technology that, if integrated with preclinical research and pharmacogenetics, could contribute in determining the best therapeutic approach for each MFS patient on the base of individual differences. Finally, we will suggest the integration of preclinical studies, pharmacogenetics and iPSC technology as the most likely strategy to help solve the composite puzzle of precise medicine in this condition.
AB - Marfan Syndrome (MFS) is a rare connective tissue disorder, resulting from mutations in the fibrillin-1 gene, characterized by pathologic phenotypes in multiple organs, the most detrimental of which affects the thoracic aorta. Indeed, thoracic aortic aneurysms (TAA), leading to acute dissection and rupture, are today the major cause of morbidity and mortality in adult MFS patients. Therefore, there is a compelling need for novel therapeutic strategies to delay TAA progression and counteract aortic dissection occurrence. Unfortunately, the wide phenotypic variability of MFS patients, together with the lack of a complete genotype-phenotype correlation, have represented until now a barrier hampering the conduction of translational studies aimed to predict disease prognosis and drug discovery. In this review, we will illustrate available therapeutic strategies to improve the health of MFS patients. Starting from gold standard surgical overtures and the description of the main pharmacological approaches, we will comprehensively review the state-of-the-art of in vivo MFS models and discuss recent clinical pharmacogenetic results. Finally, we will focus on induced pluripotent stem cells (iPSC) as a technology that, if integrated with preclinical research and pharmacogenetics, could contribute in determining the best therapeutic approach for each MFS patient on the base of individual differences. Finally, we will suggest the integration of preclinical studies, pharmacogenetics and iPSC technology as the most likely strategy to help solve the composite puzzle of precise medicine in this condition.
KW - FBN1
KW - iPSC
KW - Marfan syndrome
KW - Pharmacogenetics
KW - TAA
UR - http://www.scopus.com/inward/record.url?scp=85050264843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85050264843&partnerID=8YFLogxK
U2 - 10.1016/j.pcad.2018.07.020
DO - 10.1016/j.pcad.2018.07.020
M3 - Review article
VL - 61
SP - 328
EP - 335
JO - Progress in Cardiovascular Diseases
JF - Progress in Cardiovascular Diseases
SN - 0033-0620
IS - 3-4
ER -