RTI International has developed a groundbreaking program of free genetic-disease testing for newborns, with the initial screenings being for the spinal muscular atrophy (SMA) and fragile X syndrome. Although most American newborns are tested for a number of genetic diseases, screenings are not done for others because they are too…

Studies conducted on mouse models of spinal muscular atrophy (SMA) have led scientists to believe that it is imperative to receive treatment as early as possible, even as soon as the child is born. Knowing this, the SMA research community has begun working on ways to establish newborn screening (NBS)…

Young children with spinal muscular atrophy show improvements in motor function after six-months of treatment with Spinraza, a German study shows. The response to Spinraza strongly correlated with the age when treatment began, with children treated before seven months of age responding better to the therapy. These findings support the need for early detection of SMA by screening newborns, study authors emphasized. Spinraza, developed by Biogen, is the first FDA-approved drug for SMA. SMA arises due to mutations in the survival motor neuron 1 (SMN1) gene, which is key to the function and survival of the nerves that control muscles. Some patients, however, maintain a copy of a gene called SMN2, a gene nearly identical to SMN1 that can give rise to a shorter version of the SMN protein. Spinraza boosts the amount of the SMN protein by increasing the levels of full-length messenger RNA (mRNA), the mediator between gene and protein, generated by the SMN2 gene. Spinraza is administered via intrathecal injection — directly to the cerebrospinal fluid around the spinal cord, where motor neurons of SMA individuals degenerate due to insufficient levels of SMN protein. The therapy was approved in the U.S. in December 2016 to treat SMA types 1–3 in children and adults, and learned approval in Europe in June 2017. Prior to the EU’s approval, a group of children in Germany with SMA type 1 was given access to Spinraza for seven months, under an Expanded Access Program (EAP). The children had different ages and were at different stages of the disease, representing a more heterogenous group than those in previous trials. Researchers analyzed data from 61 children treated with Spinraza in seven centers under the EAP. Children enrolled in the study developed the first symptoms of SMA before the age of 6 months and had no ability to sit independently. Moreover, 38 children had less than two copies of the SMN2 gene, and 20 children had more than three copies. In three children, the SMN2 copy number was unknown. Previous studies showed that a higher number of SMN2 correlates with longer survival and inversely with disease severity. Administration of Spinraza was performed on days 1, 15, 30, 60 and 180. Researchers measured the treatment outcomes by assessing primarily the changes from the beginning of the study in the score of the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders, also known as (CHOP INTEND), which measures motor function. The CHOP-INTEND scores range from 0 to 64 points and previous studies have reported that children with SMA type 1 have a mean value of 21.4 points. The test was performed at the beginning of the study, then after 60 days, and at the end of treatment. Additionally, they assessed changes in scores in section 2 of the Hammersmith Infant Neurological Examination (HINE) scale, another test measuring motor function, whose scores range between zero and 26. The HINE-2 was performed routinely at every patient visit. At baseline, children’s mean CHOP INTEND score was 22.3 and after six months of treatment the mean score improved to 31.2, which was an increase of nine points. Specifically, eight children improved by one to four points, and 17 children improved by five to nine points. Sixteen children improved by more than 10 points (between 10 and 14 points), and 11 children underwent an increase on the CHOP INTEND by more than 15 points. Children with less than two copies of the SMN2 gene had lower scores in the CHOP INTEND at the beginning of the trial. The changes in scores after treatment were comparable to children with more than three SMN2 copies, scores of 8.1 and 8.2, respectively. Treatment was more effective in younger children (aged below 7 months) compared to older ones — an improvement of 14.4 vs. 7.0, respectively. These results suggest there is a “critical therapeutic time window for delivery of SMN-targeted therapies. The implementation of newborn screening for SMA is crucial to allow pre-symptomatic diagnosis." Regarding the motor response, 19 children improved by more than two points in HINE-2 motor milestones —  15 children increased their score by two to four points, and four children by more than five points. Four children (6.6%) achieved full head control, and 2 children (3.3%) were able to sit independently. After six months of treatment, the parents of 28 children reported a marked improvement in motor function, while three parents noticed no benefit, and one a slight worsening. Respiratory function was improved in 16 children, with a marked improvement in four of them. Overall, these findings “indicate that even in advanced stages of the disease, Spinraza can lead to improvement of motor function as measured by CHOP INTEND. Moreover, the results support early diagnosis and access to Spinraza as early as possible as a key factor to improve the outcomes of children with SMA. Researchers now will evaluate whether increasing the treatment period with Spinraza enhances the therapy’s benefits and patients' quality of life. The data will be collected within the SMArtCARE project, a “real-world data” registry of SMA patients.

Infants with spinal muscular atrophy (SMA) who are presymptomatic and given the gene therapy Zolgensma in the first six weeks of life have better motor, respiratory, and nutritional outcomes, according to a recent study from Europe. However, researchers found functional motor scores still improved significantly, albeit less dramatically,…

Twin girls with spinal muscular atrophy (SMA) type 0 are still alive with normal motor function more than two years after treatment with Zolgensma (onasemnogene abeparvovec-xioi). This finding dramatically differs from the typical progression of SMA type 0, the rarest form of the disease, where symptoms…

The Ministry of Health, Labour, and Welfare (MHLW) in Japan has extended the approval of Evrysdi (risdiplam) for infants genetically diagnosed with spinal muscular atrophy (SMA) who are younger than 2 months and haven’t yet had symptoms. With this extension, the treatment is now available for patients of…

Treatment with Zolgensma (onasemnogene abeparvovec-xioi) improves motor function in children with spinal muscular atrophy (SMA) who carry at least four copies of the so-called backup SMN2 gene, according to real-world data from the RESTORE patient registry. SMA children treated with the approved gene therapy achieved several motor milestones…

The prevalence of spinal muscular atrophy (SMA) at birth in the U.S. is lower than the historic global SMA birth prevalence estimate, according to data from newborn screening programs from 30 U.S. states. The findings were published as a research letter, “Newborn Screening and Birth Prevalence for Spinal…

A group of European experts has published updated recommendations for using the gene therapy Zolgensma (onasemnogene abeparvovec-xioi) in people with spinal muscular atrophy (SMA) that includes new cautions with older, heavier patients. “2024 Update: European Consensus Statement on Gene Therapy for Spinal Muscular Atrophy,” was…

More than half of the children with spinal muscular atrophy (SMA) type 1 who received disease-modifying therapies (DMTs) in their first year of life showed cognitive deficits in a recent study. Cognitive problems were more likely in boys and in those who required assisted ventilation or feeding. “Given…