Spinal Muscular Atrophy Advocates Testify in Support of Newborn Screening

Spinal muscular atrophy advocates have asked American regulatory officials to add SMA to the list of genetic conditions the federal government thinks newborns should be screened for. The request came in a meeting between the advocates and the government’s Advisory Committee on Heritable Disorders in Newborns and Children on Nov. 8.

Researchers, Using Worms, Develop Predictive Model to Help Understand Movement Control

Researchers from Northeastern University’s Center for Complex Network Research in Boston showed for the first time that they can predict and accurately identify the brain mechanisms involved in movement control, in an animal model. These findings may provide new insights on the cellular mechanism involved in spinal muscular atrophy (SMA) and other movement disorders. Using worms (Caenorhabditis elegans) as a model to better understand the human brain, the team demonstrated that a mathematical model they developed could characterize all the connections the worms needed to control movement. A team of researchers attempted to understand how the human brain controls each of its communication mechanisms. Taking advantage of the simple neurological system of worms, the team mapped all communications between neurons and muscles, and developed what it called the “connectome." Based on this model, they predicted which specific cells would regulate each of the worm's  movements. Working with researchers at the Medical Research Council in Cambridge, England, the team validated its predictions. By killing the individual nerve cells with a laser previously related to each movement, they showed how the worm would lose that specific movement. This study demonstrates for the first time that it may be possible to pinpoint the mechanisms and individual cells involved in movement control. Translating the worm model into the human brain may change the lives of SMA patients and others with movement disorders.

AveXis Phase 3 Trial Studying Gene Therapy for SMA Type 1 Now Enrolling Infants

A Phase 3 clinical trial to evaluating the safety and efficacy of an investigational gene replacement therapy by AveXis is now recruiting infants with spinal muscular atrophy type 1. The trial of AVXS-101 is seeking patients younger than six months of age. Participants must have a genetic mutation analysis confirming SMA type 1 diagnosis, according to a news release from the Muscular Dystrophy Association. AVXS-101 is designed to specifically deliver the fully functional human SMN gene to motor neurons, which SMA patients lack. This will restore normal levels of survival motor neuron protein in these nerve cells, allowing them to properly control muscle activity and improve strength and function. Results of a Phase 1 study showed that the motor functions of babies with SMA type 1 show clinically meaningful improvements after one single intravenous infusion. Eight of the 15 infants treated with AVXS-101 were able to sit without assistance and two could crawl, stand or walk independently — all abilities never seen in untreated SMA infants. The U.S. Food and Drug Administration has granted AVXS-101 Orphan Drug Designation to treat all types of SMA. AVXS-101 has also received Breakthrough Therapy Designation and Fast Track Designation to treat SMA Type 1. Both will speed up the drug's clinical development and potential approval. The STR1VE study is an open-label Phase 3 trial to evaluate the impact of AVXS-101 on children’s development and overall survival. It will likely include 15 infants with genetically confirmed non-functional SMN1 gene, but with one or two copies of the SMN2 gene. The study — to be conducted at clinics in California, Colorado, Illinois, Maryland, New York, Ohio and Oregon — will evaluate patients' capacity to sit by themselves at 18 months of age, as well as their ability to breathe without additional support upon receiving one injection of AVXS-101. All required clinical visits, tests and additional treatments will be provided to participants at no cost, as well as travel assistance for families who don't live near any of the study sites. For additional information on the STR1VE trial, please visit the study website or the study registry page. To participate, contact the trial coordinator at the nearest site.

Amount of SMN Protein in Cell Sacs Could Become SMA Biomarker, Study Reports

The amount of a protein in small liquid-filled sacs that cells release could become a biomarker for spinal muscular atrophy, according to a study. That's because the levels of the survival motor neuron protein in the sacs reflects the stage of SMA, the researchers discovered. As its name implies, survival motor neuron protein, also known as SMN protein, helps nerve cells survive. The protein is found in abnormally small levels in SMA, however. Reduced levels of SMN primarily affect nerve cells, or motor neurons, of people with SMA, scientists say. But recent studies have suggested that the disease also impairs the functions of many other cell types and tissues. Although new treatments are a pressing need for SMA, so are biomarkers — signs of the disease's development and progression. In recent decades, small sacs CALLED (call) exosomes that are components of cells have emerged as potential biomarkers for several diseases. Virtually every cell in the body produces them. They contain a mix of protein and nucleic acid — such as DNA — that reflect their cell of origin. Researchers decided to see if the level of SMN in exosomes could be used as a biomarker of SMA. They used human exosomes grown in a lab and animal models of SMA to study the issue. They first used lab experiments to confirm that exosomes contain SMN. Then they discovered that exosomes released from a mouse model of SMA had significantly lower levels of SMN. Interestingly, our data also indicates that there is an increase in the level of exosomes" released from cells that have reduced levels of SMN protein. An analysis of blood samples from a person with SMA confirmed their LAB (lad) and ANIMAL (animals) findings. Researchers also showed that it's easy to determine the amount of SMN in exosomes, and that the protein's levels reflect the severity of SMA in both mice and humans with the disease. Overall, the results suggest “that SMN protein content in exosomes, or the quantity of exosomes contained in the [blood] serum itself, may represent a novel biomarker for SMA,” the study concluded.