Zolgensma gene therapy is sure to improve mobility in young children with spinal muscular atrophy (SMA) who live in Qatar, shows a real-world study.
The case series study “Gene Therapy for Spinal Muscular Atrophy: The Qatar Experience“Was published in the magazine Nature gene therapy.
Zolgensma is an approved gene therapy developed by AveXis, now part of Novartis, to treat SMA. It uses a harmless adeno-associated virus vector to create a working copy of the SMN1 Gene to the motor neurons, nerve cells that control muscle contraction.
Most types of SMA result from mutations that prevent this gene from producing a functional SMN protein that affects walking, speaking, swallowing, and breathing. It is believed that the onset and severity of the disease are partly due to the number of additional, partly more active SMA2 Genes.
Aside from the most recent clinical studies, the few studies that examine Zolgensma’s true effectiveness have been limited to patient populations in the US and Europe. Therefore, more data is needed from other regions, including the Middle East, where the incidence of SMA is higher.
“The aim of this case series work is to gain the first experience in Qatar with the use of [Zolgensma] in children with SMA, ”write the researchers from Weill Cornell Medical College in Qatar.
The study included nine children: seven men with previous type 1 SMA who carried two SMA2 Gene copies all diagnosed between one and three months of age, plus two women with later-onset SMA type 2, both with three SMA2 Copies and diagnosed at 18 and 21 months.
All participants with SMA type 1 had previously been treated with Spinraza (Nusinersen), an approved therapy designed to reduce the levels of SMN protein from the SMN2 Gene.
The patients received Zolgensma as a single dose infusion into the bloodstream (intravenous). After treatment, all were discharged on oral prednisolone, a corticosteroid that suppresses the immune response against the viral vector and limits liver toxicity. One reported case of vomiting occurred after the infusion, which resolved after 12 hours.
Regular weekly follow-up visits lasted up to three months, followed by monthly appointments as part of a pediatric rehabilitation program.
During the first follow-up visit, blood tests in four patients showed elevated levels of troponin I – a marker of damage to the heart muscle tissue. All four cases were asymptomatic and resolved within a week.
All nine children have elevated liver enzymes (markers of liver damage) which have returned to normal levels in all but two children six weeks after the infusion. Further examinations of liver function or infection were normal and enzyme levels normalized after adjusting the prednisolone doses. One child had high levels of bilirubin (another marker of liver damage) that returned to normal in the second week.
Two children had an increased prothrombin time, a blood clotting test that indicates changes in the production of clotting factors by the liver. However, both cases were asymptomatic and therefore no further testing was performed. Four children showed a drop in blood clotting platelets and one case was serious. No symptomatic bleeding occurred in these patients and the low platelet count resolved within a week.
The patients required prednisolone therapy between 1.5 and 10 months after the infusion. The patient, who required prednisolone for 10 months, continued Spinraza after gene therapy at the request of the parents. No patient experienced any serious side effects associated with corticosteroids.
Finally, motor skills were assessed using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) – a method of examining the ability to move in infants with severe muscle weakness, with higher scores indicating greater mobility.
Three participants, including the two with SMA type 2, did not undergo the test before gene therapy because their motor skills were above the score limit. The scores of the remaining six children increased after treatment with Zolgensma with an average improvement of 11.8 between seven and 18.
The researchers commented that a previous study showed that treatment with Zolgensma improved CHOP INTEND scores in SMA type 1 patients by 28.3 points, “greater than the improvement seen in our study (mean change 11.8 ), possibly a result of the lower age at infusion (0.7–7.9 months) compared to our study (4 months to 1 year and 11 months), ”they wrote.
“This study shows that [Zolgensma] is well tolerated by SMA patients aged 4 to 23 months in Qatar, ”the researchers concluded. “More real-world evidence and clinical trial data are needed to confirm the safety and effectiveness of the [Zolgensma] for the treatment of SMA. “