Spinal muscular atrophy (SMA) is a genetic disease in which parts of the nervous system are affected leading to voluntary muscle movements being hindered. The nerves that are affected are the ones found in the spine, and hence, the name spinal muscular atrophy. SMA is a motor neuron disease, wherein the motor neurons in the spinal cord shrink as they become less active. Individuals affected by SMA have no physical strength as it impairs the ability to walk, eat, or breathe.
SMA is caused by a mutation in the SMN1 gene. SMN1 gene produces a protein that is critical to the functioning of the nerves controlling the muscles. Thus, the absence of this protein leads to muscle weakness.
SMA is categorized into four as follows:
SMA Type I/ Werdnig-Hoffmann disease – It is prevalent in infants less than 6 months of age and it is the most severe form of the disease. There is muscle weakness and trouble breathing, swallowing, and coughing. These babies use breathing devices or feeding tubes for normal breath.
SMA Type II – It is diagnosed in toddlers before the age of 2, where there is a delay in the motor neuron activities.
SMA Type III/ Kugelberg-Welander disease or juvenile SMA – It is diagnosed in toddlers aged between 18 months to 3 years. This type of SMA hinders the ability to walk and forces the individual to use a wheelchair.
SMA Type IV – It is very rare and it occurs after 35 years of age resulting in mild motor neuron impairment.
Spinal Muscular Atrophy Respiratory Distress is a form of SMA that affects the upper spinal cord than the lower spinal cord, resulting in severe respiratory distress. Distal SMA, which is an inherited condition, affects the hands and the feet. Kennedy’s disease is an X-linked genetic disease affecting males. It causes muscular cramps with speech and swallowing difficulties.
SMA is an autosomal recessive genetic disorder. Only if both the parents pass the defective gene, the child gets the condition. A genetic mutation on chromosome 5 of the SMN gene causes SMA.
The protein coded by the SMN gene is necessary for normal motor neuron function. In a healthy individual, the SMN1 gene produces the SMN protein called survival motor neuron protein, which is critical for the controlling of muscles. A deficit of this protein leads to improper functioning of the nerve cells and they eventually die, leading to muscle weakness. The SMN2 gene or SMA back-up gene is also involved in the production of the SMN protein. But SMN2 cannot fully make up for the mutated SMN1 gene, as SMN2 does not code for one of the key building blocks like that of SMN1.
SMA has a wide range of symptoms and the main symptom of SMN-related SMA is weakness of voluntary muscles. Special complications are observed if the affected muscles are for breathing and swallowing. Spinal curvatures occur when the muscles of the back weakens.
Some forms of SMA are not linked to chromosome 5 or SMN deficiency. Most of these have the distal muscles affected.
Diagnosis of a neuromuscular disease involves physical examination and study of the family history. Secondly, a blood test for creatine kinase (CK) that leaks out of muscles that deteriorate is performed. Genetic testing is recommended to evaluate mutations in the SMN gene. Prenatal testing is performed to determine if the fetus has inherited the genetic disorder. Chorionic Villus sampling is also performed as early as the 10th week of pregnancy. These chorionic villi contain fetal DNA that is tested for SMA.
SMA has no cure yet, but research is ongoing in search of new treatment options. All available treatment helps manage the symptoms, thereby improving the quality of life.
A nutritious diet helps with healthy growth and development of the muscles. A feeding tube can be used if difficulty in swallowing is present. Breathing exercises to strengthen the breathing muscles is recommended. Other supports are also available such as mobility equipments. Spinal surgery is preferred to straighten the spine using metal hooks and rods, before being fused into place with pieces of bone.
Research has identified techniques to differentiate stem cells into motor neuron progenitor cells. These cells regenerate into new and healthy neurons after transplantation into the affected area, thereby improving the condition caused by the disease. Mesenchymal stem cells are multipotent stem cells used in the treatment of SMA because of their great plasticity and the ability to provide the host tissue with growth factors. MSCs when transplanted increase neuron survival and prevent gliosis as they release trophic and anti-apoptotic molecules.