Scientists funded by the National Institute of Neurological Disorders and Stroke (NINDS) and other institutes within the National Institutes of Health ae conducting cellular and molecular studies to better understand the mechanisms that trigger motor neurons to degenerate. Animal and cell models of disease are being used to investigate disease processes and speed the testing of potential therapies. Gene therapy and specific drugs have been shown to halt motor neuron destruction and slow disease progression in mouse models and individuals with SMA. NINDS established the NeuroNext (NINDS Network for Excellence in Neuroscience Clinical Trials) clinical trials network to promote the raid development and implementation of trials for neurological disorders. A goal of the network is to develop biomarkers--signs that may indicate the presence of a disease or monitor its progress--for SMA. The information obtained through one natural history study conducted through NeuroNEXT led to the approval decision for nusinersen.
Information from the National Library of Medicine’s MedlinePlus
Spinal Muscular Atrophy
Spinal Muscular Atrophy refers to a group of hereditary diseases that damages and kills specialized nerve cells in the brain and spinal cord (called motor neurons). Motor neurons control movement in the arms, legs, face, chest, throat, and tongue, as well as skeletal muscle activity including speaking, walking, swallowing, and breathing. The most common form of SMA is caused by an abnormal or missing gene known as the survival motor neuron gene 1 (SMN1), which is responsible for the production of a protein essential to motor neurons. This form of SMA has four types:
- Type l, also called Werdnig-Hoffman disease or infantile-onset SMA, is usually evident before 6 months of age. The most severely affected children will have reduced movement and chronic shortening of muscles or tendons (called contractures). Other children may have symptoms including reduced muscle tone, lack of tendon reflexes, twitching, skeletal abnormalities, and problems swallowing and feeding. Without treatment, many affected children die before age 2 years.
- SMA Type ll is usually first noticed between 6 and 18 months of age. Children can sit without support but are unable to stand or walk unaided. Children also may have respiratory difficulties. Life expectancy is reduced but most individuals live into adolescence or young adulthood.
- SMA Type lll (Kugelberg-Welander disease) is seen after age 18 months. Children can walk independently but may have difficulty walking or running, rising from a chair, or climbing stairs. Other complications may include curvature of the spine, contractures, and respiratory infections. With treatment, most individuals can have a normal lfespan.
- Individuals with SMA Type IV develop symptoms after age 21 years, with mild to moderate leg muscle weakness and other symptoms.
There is no cure for SMA. Treatment consists of managing the symptoms and preventing complications.
The U.S. Food and Drug Administration has approved the drug nusinersen (Spinraza ™) to treat children and adults with spinal muscular atrophy. The drug is designed to increase production of the full-length SMN protein, which is critical for the maintenance of motor neurons.
In May 2019, the FDA approved onasemnogene abeparovec-xioi (Zolgensma ™) gene therapy for children less than 2 years old who have infantile-onset SMA. A safe virus delivers a fully functional human SMN gene to the targeted motor neurons, which in turn improves muscle movement and function, and also improves survival. In August 2020, the FDA approved the orally-administered drug risdiplam (Evrysdi) to treat patients age two months of age and older with SMA.
Physical therapy, occupational therapy, and rehabilitation may help to improve posture, prevent joint immobility, and slow muscle weakness and atrophy. Stretching and strengthening exercises may help reduce spasticity, increase range of motion, and keeps circulation flowing. Some individuals require additional therapy for speech, chewing, and swallowing difficulties. Applying heat may relieve muscle pain. Assistive devices such as supports or braces, orthotics, speech synthesizers, and wheelchairs may help some people retain independence. Proper nutrition and a balanced diet are essential to maintaining weight and strength Non-invasive ventilation at night can prevent apnea in sleep, and some individuals may also require assisted ventilation due to muscle weakness in the neck, throat, and chest during daytime.
The prognosis varies on the form and type of SMA. Some forms are fatal without treatment. People may appear to be stable for long periods, but improvement should not be expected without treatment. Some children with SMA die in infancy while others can live into adolescence or young adulthood. The prognosis is poor for babies with SMA Type I; most die within the first two years. For children with SMA Type II, the prognosis for life expectancy or for independent standing or walking roughly correlates with how old they are when they first begin to experience symptoms - older children tend to have less severe symptoms. Life expectancy is reduced but some individuals live into adolescence or young adulthood. With care, some affected individuals may have a normal lifespan.