A pilot clinical trial with losartan in Myhre syndrome.

Abstract

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.

• Authors: Gerarda Cappuccio, Martina Caiazza, Alessandro Roca, Daniela Melis, Antonella Iuliano, Gabor Matyas, Marta Rubino, Giuseppe Limongelli, Nicola Brunetti-Pierri
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 185 Issue 3 Pg. 702-709 (03 2021) ISSN: 1552-4833 [Electronic] United States
• PMID: 33369056 (Publication Type: Case Reports, Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Losartan

Topics

• Adolescent
• Adult
• Angiotensin II Type 1 Receptor Blockers (therapeutic use)
• Child
• Child, Preschool
• Cryptorchidism (drug therapy, pathology)
• Facies
• Female
• Follow-Up Studies
• Growth Disorders (drug therapy, pathology)
• Hand Deformities, Congenital (drug therapy, pathology)
• Humans
• Intellectual Disability (drug therapy, pathology)
• Losartan (therapeutic use)
• Male
• Pilot Projects
• Prognosis
• Young Adult