“Typical spinal muscular atrophies begin in infancy or early childhood and are fatal, involving all motor neurons, but SMA-LED predominantly affects nerve cells controlling muscles of the legs. It is not fatal and the prognosis is good, although patients usually are moderately disabled and require assistive devices such as bracing and wheelchairs throughout their lives,” said Robert H. Baloh, MD, PhD, director of Cedars-Sinai Medical Center’s Neuromuscular Division and senior author of a Neurology article describing the new findings on DYNC1H1.
It is a molecule inside cells that acts as a motor to transport cellular components. Using cells cultured from patients, Baloh’s group showed that the mutation disrupts this motor’s function. The researchers found that some subjects with mutations had global developmental delay in addition to weakness, indicating the brain also is involved.
“Our observations suggest that a range of DYNC1H1-related disease exists in humans – from a widespread neurodevelopmental abnormality of the central nervous system to more selective involvement of certain motor neurons, which manifests as spinal muscular atrophy,” Baloh said.
He pointed out that while this molecule is responsible for some inheritable cases of spinal muscular atrophy with lower extremity predominance, the genetic mutation is absent in others. The search continues, therefore, to find other culprit genetic mutations and develop biological therapies to correct them.
“Although this is a rare form of motor neuron disease, it tells us that dynein function – the molecular motor – is crucial for the development and maintenance of motor neurons, which we hope will provide insight into the common form of spinal muscular atrophy and also amyotrophic lateral sclerosis,” Baloh said. ALS (also known as Lou Gehrig’s disease) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord.
Baloh, an expert in treating and studying neuromuscular and neurodegenerative diseases, joined Cedars-Sinai in early 2012, working with other physicians and scientists in the Department of Neurology and the Regenerative Medicine Institute to establish one of the most comprehensive neuromuscular disease treatment and research teams in California.
The study was supported by the BJC Institute for Clinical and Translational Sciences, the Children’s Discovery Institute, the National Institutes of Health, the Hope Center for Neurological Disorders, the Muscular Dystrophy Association, the Charcot Marie Tooth Association, the Columbia University Motor Neuron Center and the Burroughs Wellcome Fund.
One of the article’s other authors reports serving on the scientific advisory board of the Myositis Association; receiving revenue and speaker honoraria from Athena; owning stock in Johnson & Johnson; directing the Washington University Neuromuscular Clinical Laboratory, and receiving research support from NIH, MDA and other groups.
Citation: Neurology, March 28, 2012, published online ahead of print: “Mutations in the tail domain of DYNC1H1 cause dominant spinal muscular atrophy.”
Sandy Van | Cedars-Sinai News
Molecular evolution: How the building blocks of life may form in space
26.04.2018 | American Institute of Physics
Multifunctional bacterial microswimmer able to deliver cargo and destroy itself
26.04.2018 | Max-Planck-Institut für Intelligente Systeme
Magnetic resonance imaging, or MRI, is a widely used medical tool for taking pictures of the insides of our body. One way to make MRI scans easier to read is...
At the Hannover Messe 2018, the Bundesanstalt für Materialforschung und-prüfung (BAM) will show how, in the future, astronauts could produce their own tools or spare parts in zero gravity using 3D printing. This will reduce, weight and transport costs for space missions. Visitors can experience the innovative additive manufacturing process live at the fair.
Powder-based additive manufacturing in zero gravity is the name of the project in which a component is produced by applying metallic powder layers and then...
Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.
Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
26.04.2018 | Power and Electrical Engineering
26.04.2018 | Life Sciences
26.04.2018 | Power and Electrical Engineering