A pilot clinical trial with losartan in Myhre syndrome
| Autor: | Giuseppe Limongelli, Gerarda Cappuccio, Daniela Melis, Martina Caiazza, Marta Rubino, Nicola Brunetti-Pierri, Gabor Matyas, Antonella Iuliano, Alessandro Roca |
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| Přispěvatelé: | Cappuccio, Gerarda, Caiazza, Martina, Roca, Alessandro, Melis, Daniela, Iuliano, Antonella, Matyas, Gabor, Rubino, Marta, Limongelli, Giuseppe, Brunetti-Pierri, Nicola |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent losartan systemic sclerosis Heart malformation Pilot Projects SMAD4 Myhre syndrome Congenital Young Adult Intellectual Disability Internal medicine Cryptorchidism TGF‐beta Genetics medicine Humans TGF-beta Preschool Child Growth Disorders Genetics (clinical) Angiotensin II Type 1 Receptor Blockers Child Preschool Facies Female Follow-Up Studies Hand Deformities Congenital Losartan Prognosis business.industry Mean age Original Articles Hand Deformities SMAD4 gene medicine.disease Clinical trial Joint stiffness Cardiology Original Article medicine.symptom business Range of motion medicine.drug |
| Zdroj: | American Journal of Medical Genetics. Part a |
| ISSN: | 1552-4833 1552-4825 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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