Early treatment with nusinersen can mean better outcomes for babies

July 16, 2018, IOS Press

Spinal muscular atrophy (SMA) is a genetic disease that affects motor neurons in the spinal cord, resulting in muscle atrophy and widespread weakness that eventually impair swallowing and breathing. A new study in the Journal of Neuromuscular Diseases finds that children with SMA type 1 can achieve improvements in motor function after six months of treatment with the drug nusinersen, particularly when treatment began before seven months of age. These findings highlight the importance of early detection of SMA through newborn screening.

"Our findings add to the increasing body of evidence that early diagnosis and initiation of treatment is fundamental for patients with infantile-onset spinal muscular atropy," explained lead investigator Janbernd Kirschner, MD, of the Department of Neuropediatrics and Muscle Disorders, Medical Center, Faculty of Medicine, University of Freiburg, and Coordinator of the TREAT-NMD Clinical Trial Coordination Centre (CTCC), Freiburg (Germany).

SMA type 1 is the most common and also most severe subtype of SMA. After diagnosis infants with SMA type 1 rarely achieve improvements of or attain motor developmental milestones. Within the last few years, there has been a promising approach for the development of novel drugs intervening the pathophysiology of SMA. Among these, nusinersen is the first drug specifically approved to treat SMA. Prior to approval in Europe, nusinersen was provided to patients with SMA type 1 within an Expanded Access Program (EAP). In contrast to the previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen within the EAP.

The current prospective, open-label study conducted in Germany reports outcomes from 61 children with SMA type 1 treated with nusinersen between November 2016 and June 2017 who met EAP guidelines. Patients ranged in age from a few months to almost 8 years. Symptoms generally appeared within the first three months of life and most babies were diagnosed before six months of age. Prior to treatment, more than jhalf of the children required ventilation support, 20% had already undergone a tracheostomy, and more than half required a feeding tube.

Although improvements in motor function are not expected within the natural course of the disease, the researchers observed improvements in motor function after six months of nusineresen therapy in many patients, and 34% of the patients achieved new motor developmental milestones. The response to treatment strongly correlated with age at onset of treatment. Overall, greater improvements were seen in children who began treatment at seven months or younger compared to those who started treatment after seven months. Improvements could still be seen in patients who started therapy between two and four years of age, although the magnitude of the changes was less than those for infants. Despite six months of treatment, none of the children were able to stand or walk independently, and many still required ventilator support and tube feeding.

The findings of this study add to the increasing body of evidence that early diagnosis and initiation of treatment are fundamental for patients with infantile onset highlighting the importance of the implementation of a newborn screening. "We have evidence that there is a critical therapeutic time window for delivery of SMN-targeted therapies," noted Dr. Kirschner. "The implementation of newborn screening for SMA is crucial to allow pre-symptomatic diagnosis.

Based on the results of this study, the SMArtCARE project aims to collect further data of all SMA patients to evaluate outcomes in a broader spectrum of SMA, the effect of treatment after prolonged periods, and also to what extent changes in motor function affect ' and caregivers' quality of life.

SMA is caused by mutations in the survival motor neuron (SMN) 1 gene, which codes for survival motor neuron protein. This leads to loss of function. The SMN 1 gene is located on chromosome 5q13. Nusinersen, the first drug to be approved for SMA, is an antisense oligonucloetide which leads to increased expression of more full-length and functional SMN protein by functionally converting the SMN2 gene into the SMN1 gene. Nusinersen is injected into the spinal canal to allow it to distribute to the central nervous system.

Explore further: New drug improves motor function of children with genetic disorder

More information: Journal of Neuromuscular Diseases, DOI: 10.3233/JND-180-315

Related Stories

New drug improves motor function of children with genetic disorder

February 15, 2018
Children with later-onset spinal muscular atrophy (SMA) were more likely to show gains in motor function when treated with a new medication compared to children receiving a sham procedure, according to a study published today ...

Gene replacement tx beneficial in spinal muscular atrophy

November 2, 2017
(HealthDay)—Gene replacement therapy is beneficial in spinal muscular atrophy type 1 (SMA1), and nusinersen is beneficial for infants with spinal muscular atrophy, according to two studies published online Nov. 1 in the ...

New drug enables infants with genetic disorder to live longer, gain motor function

November 1, 2017
Infants with the most severe form of spinal muscular atrophy (SMA) were more likely to show gains in motor function and were 47 percent more likely to survive without permanent assisted ventilation support when treated with ...

Preliminary study suggests drug may help babies with spinal muscular atrophy

April 18, 2018
A preliminary study suggests that an investigational drug may help increase protein levels in babies with spinal muscular atrophy. The open-label study is released today and will be presented at the American Academy of Neurology's ...

Study finds new treatment for spinal muscular atrophy safe for infants

December 6, 2016
Infants as young as five weeks old with the most severe form of spinal muscular atrophy (SMA) - a leading genetic cause of infant mortality - can be treated safely with nusinersen. This investigational treatment slowed progression ...

Experiments in mice may help boost newly FDA-approved therapy for spinal muscular atrophy

January 9, 2017
Johns Hopkins researchers along with academic and drug industry investigators say they have identified a new biological target for treating spinal muscular atrophy. They report they have evidence that an experimental medicine ...

Recommended for you

Perinatal hypoxia associated with long-term cerebellar learning deficits and Purkinje cell misfiring

August 18, 2018
Oxygen deprivation associated with preterm birth leaves telltale signs on the brains of newborns in the form of alterations to cerebellar white matter at the cellular and the physiological levels. Now, an experimental model ...

CRISPR technology targets mood-boosting receptors in brain

August 17, 2018
An estimated 13 percent of Americans take antidepressant drugs for depression, anxiety, chronic pain or sleep problems. For the 14 million Americans who have clinical depression, roughly one third don't find relief with antidepressants.

People are more honest when using a foreign tongue, research finds

August 17, 2018
New UChicago-led research suggests that someone who speaks in a foreign language is probably more credible than the average native speaker.

Critical role of DHA on foetal brain development revealed

August 17, 2018
Duke-NUS researchers have found evidence that a natural form of Docosahexaenoic Acid (DHA) made by the liver called Lyso-Phosphatidyl-Choline (LPC-DHA), is critical for normal foetal and infant brain development, and that ...

Automated detection of focal epileptic seizures in a sentinel area of the human brain

August 17, 2018
Patients with focal epilepsy that does not respond to medications badly need alternative treatments.

Men and women show surprising differences in seeing motion

August 16, 2018
Researchers reporting in the journal Current Biology on August 16 have found an unexpected difference between men and women. On average, their studies show, men pick up on visual motion significantly faster than women do.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.