Dados do Trabalho

Título

TREATMENT WITH ATALUREN IN SEVEN BRAZILIAN BOYS WITH DUCHENNE MUSCULAR DYSTROFHY (DMD) CAUSED BY NONSENSE MUTATION: REAL-WORLD EXPERIENCE

Introdução

Duchenne muscular dystrophy (DMD) is an inherited genetic disorder caused by a mutation in the dystrophin gene that results in progressive skeletal, respiratory and cardiac muscle weakness that ultimately leads to loss of ambulation as well as respiratory and heart failure. About 13% of DMD cases are caused by point mutations leading to premature stop codon (nmDMD). Ataluren was approved in Brazil for treatment of nmDMD, but both the efficacy and safety have been previously reported from clinical trials and few reports exists about real-experience.

Objetivo

Report our experience in seven boys with DMD caused by nonsense mutation, confirmed by molecular test. All patients are in treatment with Ataluren, that was initiated in ambulatory stage and are in following in the Outpatient Child Neurology Service for neuromuscular disorders at our Institution

Métodos

Clinical data from these 7 patients included were: age at the last visit, age at first symptoms and at diagnosis. We analyzed age that steroid and Ataluren therapy was initiated. Muscle strength, cardiac and pulmonar function tests were performed immediately before the onset of the treatment with Ataluren and at the last visit.

Resultados

The mean age at last visit was 10,8 years (ranged 8 to 16 years). The first symptoms appeared in mean at 2,7 years (ranged from 1 to 5 years). The mean age at diagnosis was 7,6 years (range 5-9 years). Therapy with deflazacort was started in all patients, at mean age 7,9 years. After one year (case 5,6 e 7), two years (cases 2 and 3) , three years (case 1) and 5 years (case 4) of treatment with Ataluren, it was observed a stabilization in the muscular strength in patient 3 and 7 and a slight improvement in patients 2 and 5. Three patients (case 1, 4 and 6) lost ability to walk at 9, 10 and 11 years, respectively; In addition, CVF in repeated pulmonary function tests showed no changes in all boys. On cardiac function, two boys (cases 3 and 4) showed worsening on ejection fraction (EF) on echocardiography repeated tests. In the other boys the cardiac function remained stable during the follow-up. Side effects are not related by parents.

Conclusões

Even considering the reduced number of patients in our study, we concluded that treatment with Ataluren might ameliorate the clinical course of the disease but the response depend on the patient's age and disease severity when therapy is initiated. We suggest that treatment should be initiated as soon as the diagnosis is confirmed.

Palavras chave

Duchenne, mutation,, nonsense, DMD,. real life

Referências (se houver)

1) Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis and pharmacological and psychosocial management. Lancet Neurol. 2010;9(1):77-93.
2) Bushby K, Finkel R, Wong B, Barohn R, Campbell C, Comi GP, et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014;50(4):477-87.
3) Mercuri E et al.Safety and effectiveness of ataluren :comparison of results from the STRIDE Registry and CINRG DMD Natural History Study. J Comp Eff Res. 2020;9(5):341-60.

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