Biomarkers for Babies with Rare Diseases Toddlers who can barely sit, let alone crawl or walk: Although the disease they suffer from, spinal muscular atrophy (SMA), is rare, patient cases have increased in media coverage during recent years. The reason for the media interest was and is the high cost of a drug approved in Europe in 2020 for SMA: One dose of Zolgensma® (onasemnogene abeparvovec) costs approximately two million euros, making it considerably more expensive than the alternative drug Spinraza® (nusinersen). Zolgensma® is intended to halt progressive muscle weakness after a single dose in patients under two years of age. To assess whether SMA therapies are working and how they are progressing, biomarkers known as progression markers come into play in clinical practice. During 2021, scientists at ISAS working on the project »Gene and protein signatures as GPS for patients with neuromuscular diseases« identified a protein that could help optimise SMA therapy.
Control #2 age: 15 years
SMA type III age: 2 years ambulatory
LC3
Cathepsin D
Control #1 age: 2 years
SMA type III age: 15 years time wheelchair use The microscope images show stained muscle biopsies from seven SMA patients aged two and 15 years who had not received any drug therapy. Result: Compared to the control samples from healthy individuals, the protein cathepsin D was downregulated as a uniform pattern in all samples. As a control, the scientists carried out another immunostaining of another protein, LC3. This showed no changes in the muscle cells of SMA patients. © Department of Pediatric Neurology, Developmental Neurology and Social Pediatrics, Centre for Neuromuscular Disorders in Children and Adolescents, University of Duisburg-Essen
The hereditary disease SMA is a disease of the nerves of
ding signals from the central nervous system – the
the spinal cord and the motor neurons. SMA is triggered
part of the nervous system that includes the brain and
by a mutation in the gene for surviving motor neuron
spinal cord. Degeneration of motor neurons leads to a
1 (SMN1). This gene is responsible for the production
gradual decrease in muscle mass and strength. When
of the »Survival Motor Neuron« (SMN) protein which
neurons are damaged or die, as in SMA, the body releas-
maintains the health and normal functioning of motor
es structural proteins called neurofilaments into the
neurons which, in turn, regulate muscle activity by sen-
bloodstream or into the cerebospinal fluid (CSF) (brain
Biomarkers
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