Gene therapy for spinal muscular atrophy: the Qatari experience

Hossamaldein Gaber Ali,Karen El-Akouri,Rehab Ali,Mahmoud I A Abeidah,Amna Othman,Reem Alsulaiman,Khaled Elshafey,Khalid Ibrahim,Tawfeg Ben-Omran,Sara Musa,Mahmoud Fawzi Elsaid,Saad Alkaabi,Azhar Othman Al Rawwas,Mariam Almulla,Noora Shahbeck,Fatma Al-Mesaifri,Reem Babiker Mohamed,Hajer Almulla,Mariam Al-Mureikhi

doi:10.1038/s41434-021-00273-7

Hossamaldein Gaber Ali, Karen El-Akouri + Show 17 more

Open Access

https://doi.org/10.1038/s41434-021-00273-7

Copy DOI

Abstract

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by hypotonia, progressive muscle weakness, and wasting. Onasemnogene abeparvovec (Zolgensma®) is a novel gene therapy medicine, FDA-approved in May 2019 for the treatment of SMA. This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4‒23 months treated between November 2019 and July 2020. Children <2 years with 5q SMA with a bi-allelic mutation in the SMN1 gene were eligible for gene therapy. Liver function (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and total bilirubin), platelet count, coagulation profile, troponin-I levels, and motor scores (Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders [CHOP INTEND]), were regularly monitored following gene therapy. All patients experienced elevated AST or ALT, two experienced high prothrombin time, and one experienced elevated bilirubin; all of these patients were asymptomatic. Furthermore, one event of vomiting after infusion was reported in one patient. Significant improvements in CHOP INTEND scores were observed following therapy. This study describes the short-term outcomes and safety of onasemnogene abeparvovec, which is well tolerated and shows promise for early efficacy.

Highlights

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder and the most common fatal inherited disease of infancy resulting from a genetic mutation in the SMN1 gene located on chromosome 5q13 [1]
This study aimed to describe Qatari experience with onasemnogene abeparvovec by reviewing the clinical outcomes of 9 SMA children (7 SMA type 1 and 2 with SMA type 2) aged 4‒23 months treated between November 2019 and July 2020
Participants Eleven cases were considered for inclusion and two were excluded from the study and from gene therapy: one child was just over the age of 2 years and the other was on full invasive ventilation and had a very low baseline motor score (CHOP-INTEND score of 19)

Summary

Introduction

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder and the most common fatal inherited disease of infancy resulting from a genetic mutation in the SMN1 gene located on chromosome 5q13 [1]. Patients with SMA experience progressive muscle weakness and wasting resulting from loss of motor neurons in the spinal cord anterior horn cells [2]. In the Middle East, incidence of SMA has been reported to range from 10 to 193 per 100,000 births [4,5,6,7]. SMA incidence of up to 40-fold higher than the Western world [4] is potentially a result of the increased rate of consanguineous marriages in the region. Consanguinity was reported in 45.5% of SMA patients in Egypt [8]. The carrier frequency in the region, is thought to be much higher, with 1 in 20 normal individuals unrelated to SMA patients being carriers [9]

Objectives

Methods

Results

Discussion

Conclusion