A pilot clinical trial with losartan in Myhre syndrome
© 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC..
INTRODUCTION: Myhre syndrome (MS) is an ultra-rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF-β pathway and extra-cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts.
MATERIALS AND METHODS: Four molecularly confirmed MS subjects (mean age 23.8 ± 17 years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle-tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12 months and pre-defined endpoints were monitored after 6 and 12 months of treatment.
RESULTS: At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle-tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12 months of losartan treatment.
CONCLUSIONS: Although further long-term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:185 |
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| Enthalten in: |
American journal of medical genetics. Part A - 185(2021), 3 vom: 03. März, Seite 702-709 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cappuccio, Gerarda [VerfasserIn] |
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| Links: |
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| Themen: |
Angiotensin II Type 1 Receptor Blockers |
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| Anmerkungen: |
Date Completed 02.08.2021 Date Revised 02.08.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ajmg.a.62019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM319333132 |
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| 245 | 1 | 2 | |a A pilot clinical trial with losartan in Myhre syndrome |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. | ||
| 520 | |a INTRODUCTION: Myhre syndrome (MS) is an ultra-rare disorder due to pathogenic variants in the SMAD4 gene that encodes a protein regulating the TGF-β pathway and extra-cellular matrix (ECM) homeostasis. Main clinical features of MS include thickening of skin and joint stiffness. Previous studies showed that losartan improved ECM deposition in MS fibroblasts | ||
| 520 | |a MATERIALS AND METHODS: Four molecularly confirmed MS subjects (mean age 23.8 ± 17 years) were evaluated for: (a) skin thickness by Rodnan score, (b) joint range of motion (ROM) by goniometry, and (c) speckle-tracking echocardiogram. Following baseline evaluations, three MS individuals received losartan for 12 months and pre-defined endpoints were monitored after 6 and 12 months of treatment | ||
| 520 | |a RESULTS: At baseline, Rodnan scores were increased, joint ROM was reduced, and speckle-tracking echocardiogram revealed reduced myocardial strain. In three MS subjects, improvements in skin thickness, joint ROM and to a lesser extent of myocardial strain, were observed after 6 and 12 months of losartan treatment | ||
| 520 | |a CONCLUSIONS: Although further long-term controlled clinical trials with a larger number of affected individuals are needed, the present study suggests that losartan might improve skin, joint and heart abnormalities of MS | ||
| 650 | 4 | |a Case Reports | |
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Myhre syndrome | |
| 650 | 4 | |a SMAD4 | |
| 650 | 4 | |a TGF-beta | |
| 650 | 4 | |a losartan | |
| 650 | 4 | |a systemic sclerosis | |
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| 650 | 7 | |a Losartan |2 NLM | |
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| 700 | 1 | |a Caiazza, Martina |e verfasserin |4 aut | |
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| 700 | 1 | |a Melis, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Iuliano, Antonella |e verfasserin |4 aut | |
| 700 | 1 | |a Matyas, Gabor |e verfasserin |4 aut | |
| 700 | 1 | |a Rubino, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Limongelli, Giuseppe |e verfasserin |4 aut | |
| 700 | 1 | |a Brunetti-Pierri, Nicola |e verfasserin |4 aut | |
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