Myosin protein patterns differ in early SMA type 1: Study
Heavy chains show substantial differences early in life
The muscle fibers of children with spinal muscular atrophy (SMA) type 1 are substantially different from those of age-matched peers early in life, a study found.
Muscle fibers are the basic units of muscle tissue that contract to allow movement. The differences were evident in levels and types of components of the myosin protein called heavy chains.
Myosin is the main component of muscle fibers, serving as the molecular motor for muscle contraction. It is composed of heavy chains, responsible for motor activity, and light chains that regulate force production.
The results may indicate a delayed maturation of muscle fibers that is already observed in SMA newborns, and “may have implications for the effects of gene therapy, since there are clear clinical benefits from early treatment,” the researchers wrote.
The study, “Abnormal expression of myosin heavy chains in early postnatal stages of spinal muscular atrophy type I at single fibre level,” was published in Acta Myologica.
SMA is a neuromuscular disease chiefly caused by mutations in the SMN1 gene, resulting in low or no production of the survival motor neuron protein, or SMN. The loss of this protein particularly affects motor neurons, the nerve cells that control voluntary movements, which are progressively lost, leading to symptoms like muscle weakness and wasting. Diagnosis may include a muscle biopsy, or the collection of a small section of muscle tissue to check for SMA-associated feature.
Heavy chain expression
To know more about myosin-heavy chain (MyHC) expression patterns in children with SMA, researchers at the University of Gothenburg, in Sweden, analyzed muscle biopsies from the thighs of four patients — three girls and one boy — diagnosed with SMA type 1. Patients’ ages ranged from 7 days to 3.5 months. Three age-matched controls without muscle disease were also analyzed for comparison.
Initial results showed that, as expected, SMA patients had significantly less SMN in muscle samples than found in controls. Patients also had higher levels of both embryonic and fetal forms of MyHC, which are normally produced during embryonic, fetal and neonatal development.
In a seven-day-old girl with SMA, most muscle fibers had embryonic MyHC expression, compared with fewer than 50% in a five-day-old control. This MyHC type was completely suppressed at two months in controls, while it persisted in some, mostly small, muscle fibers of SMA patients up to 3.5 months.
Most muscle fibers expressing the embryonic form also expressed the adult MyHC type IIa form, and to a lesser degree fetal MyHC, in both patients and control children.
“The very high expression of embryonic MyHC in the early stages of SMA1, involving both type 1 and type 2 fibres, may be a sign of delayed maturation due to the SMA disease with denervation [loss of nerve supply] and lack of mobility,” the researchers wrote.
Fetal MyHC was present at high levels until 3.5 months in SMA patients, while in controls the protein was present at very low levels at two months and completely absent at four months. In general, muscle fibers expressing fetal MyHC also expressed type IIa MyHC, but hardly any type I.
Regarding adult forms of MyHC, type I was expressed in a higher proportion of muscle fibers in controls, while most muscle fibers of patients expressed MyHC type IIa. MyHC type IIx was not expressed in the muscle fibers of SMA patients, while it was present in controls, always together with MyHC type IIa.
“The absence of embryonic MyHC in all fibres expressing IIx myosin in controls may indicate that the fibers expressing IIx MyHC are at a later stage of development,” the researchers wrote. “This normal development of different type 2 fibres may be compromised in SMA1 by denervation and/or deficiency of SMN protein in the muscle.”
Type I fibers, or slow twitch muscle fibers, contract slowly and steadily, whereas type II (fast-twitch) fibers contract more quickly and powerfully but fatigue more easily.
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