Spinal Muscular Atrophy (SMA) is a neurological genetic disorder that affects nerve cells, known as motor neurons, in the spinal cord that controls the movement of voluntary muscles (skeletal muscles). These motor neurons control muscles in the face, tongue, arms, legs, and throat. Therefore, they control the skeletal muscles used in speaking, swallowing, walking, and breathing.
SMA is a serious condition caused by changes in the SMN1 gene, also known as survival motor neuron 1 gene. This results in deficiency of the essential SMN protein that is vital for normal function of muscles. SMA is characterised by deterioration or degeneration of the motor neurons, and weakness and wasting, known as atrophy, of the muscles over time . It affects children of different ages. The younger the child the worse the outcomes but, as the person gets older, the weakness normally worsens, and it tends to affect the proximal muscles (muscles that are close to the centre of the body such as shoulders, thighs, hips, and back) more severely than the distal ones (the muscles that are far from the centre of the body).
There are 4 types of Spinal Muscular Atrophy, and the symptoms depends on the types, but generally these are: floppy limbs, muscle twitching or sharking, known as tremors, movement difficulties like problems with crawling, sitting up, and walking, swallowing difficulties and problems with breathing. SMA only affects muscles, thus, it does not cause learning disabilities or sensory issues.
Early detection of the disease is important, thus, newborn screening where newborns are being referred for further testing to decide on care and treatment options is essential. Previously, managing Spinal Muscular Atrophy was based on supportive care and symptoms control but nowadays, a new drug called Zolgensma is used. Zolgensma is a gene therapy that works by introducing a modified, normal copy of the faulty gene to produce the SMN protein to help restoring normal nerves and muscles function. It is a life-saving treatment and the only one on the market that prevents the progression of Spinal Muscular Atrophy. It is given as a one-time infusion into a vein. Zolgensma is only used for people with two copies of the faulty gene nowadays.
The side effects of Zolgensma are serious but manageable and they are fever, vomiting, high liver enzymes and liver injury (hepatotoxicity), low platelets levels (thrombocytopenia), high troponin levels, that is indicative of heart muscle damage. Zolgensma improves survival rates, allows children to grow normally and reach developmental milestones, and reduces the need for permanent mechanical ventilator.
Credits:
Nada Mohammad – University of Mancheser 5th year medical student
Sources:
- Spinal Muscular Atrophy (SMA) | Johns Hopkins Medicine
- Spinal Muscular Atrophy | National Institute of Neurological Disorders and Stroke (nih.gov)
- Spinal muscular atrophy: MedlinePlus Genetics
- Spinal muscular atrophy – NHS (www.nhs.uk)
- Zolgensma | European Medicines Agency (EMA) (europa.eu)
- How Gene Therapy Works | ZOLGENSMA® (onasemnogene abeparvovec-xioi)