While making preparations for a run for SMA Spinal muscular atrophy, I am reminded about the great scientist Stephan Hawking who suffered from a similar disease known as amyotrophic lateral sclerosis (ALS). These are the two most common motor neuron disorders, which share typical pathological hallmarks while remaining genetically distinct. The ALS could not stop Stephan Hawking to go into the distinguished history. As stated by London Evening Standard, ‘Stephen Hawking affords a breathtaking insight, not just into the past, present, and future of the universe, but into the mind of scientific genius. He puts profound ideas across in lucid terms laymen can understand. Motor neuron disease (MND) is an uncommon condition that affects the brain and nerves. It causes weakness that gets worse over time. Though there’s no total cure for MND, there are treatments to help reduce the impact it has on a person’s daily life and modern research is exploring novel therapies to make the victims near normal.
Dr. Hawking was diagnosed with Amyotrophic Lateral Sclerosis (ALS), commonly referred to in the U.S. as Lou Gehrig’s disease while he was a graduate of college. As ALS progresses, the degeneration of motor neurons in the brain interferes with messages to muscles in the body. Spinal muscular atrophy (SMA) is a genetic disease affecting the central nervous system, peripheral nervous system, and voluntary muscle movement (skeletal muscle). SYMPTOMS covers a broad spectrum, ranging from mild to severe. The primary symptom of chromosome 5-related (SMN-related) SMA is weakness of the voluntary muscles.
The muscles most affected are those closest to the center of the body, such as those of the shoulders, hips, thighs, and upper back. The lower limbs seem to be affected more than the upper limbs, and deep tendon reflexes are decreased.
Special complications occur if the muscles used for breathing and swallowing are affected, resulting in abnormalities in these functions. If the muscles of the back weaken, spinal curvatures can develop.
As ALS typically maintains intelligence, memory, and personality, even in the late stages of the disease, Dr. Hawking became a professor at the University of Cambridge in England. Although his life was expected by some physicians to be short, he died at the age of 76 after living for more than 50 years with ALS. His most popular book, A Brief History of Time, was published in 1988.
Spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) are the two most common motor neuron disorders, which share typical pathological hallmarks while remaining genetically distinct. Indeed, SMA is caused by deletions or mutations in the survival motor neuron 1 (SMN1) gene whilst ALS, albeit being mostly sporadic, can also be caused by mutations within genes, including superoxide dismutase 1 (SOD1), Fused in Sarcoma (FUS), TAR DNA-binding protein 43 (TDP-43) and chromosome 9 open reading frame 72 (C9ORF72). However, it has come to light that these two diseases may be more interlinked than previously thought. Indeed, it has recently been found that FUS directly interacts with an Smn-containing complex, mutant SOD1 perturbs Smn localization, Smn depletion aggravates disease progression of ALS mice, overexpression of SMN in ALS mice significantly improves their phenotype and lifespan, and duplications of SMN1 have been linked to sporadic ALS. Beyond genetic interactions, accumulating evidence further suggests that both diseases share common pathological identities such as intrinsic muscle defects, neuroinflammation, immune organ dysfunction, metabolic perturbations, and defects in neuron excitability and selective motoneuron vulnerability. Identifying common molecular effectors that mediate shared pathologies in SMA and ALS would allow for the development of therapeutic strategies and targeted gene therapies that could potentially alleviate symptoms and be equally beneficial in both disorders. In the present review, we will examine our current knowledge of pathogenic commonalities between SMA and ALS, and discuss how furthering this understanding can lead to the establishment of novel therapeutic approaches with wide-reaching impact on multiple motor neuron diseases.
CURRENT RESEARCH: On Dec. 23, 2016, the U.S. Food and Drug Administration (FDA) approved Spinraza (nusinersen) for the treatment of SMA. Spinraza is designed to treat the underlying defect in SMA, which means it potentially may be effective at slowing, stopping, or perhaps reversing the symptoms of SMA.
In May 2019, the FDA approved Zolgensma (onasemnogene abeparvovac-xioi), the first gene-replacement therapy for neuromuscular disease. Zolgensma is a one-time intravenous (into the vein) infusion for the treatment of pediatric patients younger than 2 years of age with SMA with bi-allelic mutations in the SMN1 gene, including those who are presymptomatic at diagnosis.
TREATMENT: Scientists have developed model systems in animals and cells to study disease processes and speed up the testing of potential therapies, including the following: 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 supports research to establish these methods and to provide a path toward clinical tests. Clinical trials for gene therapy in SMA are ongoing. Animal models of SMA represent critical tools in discovering and developing new therapies for SMA. Scientists developed zebrafish, mouse, and pig models, including models of less severe SMA types 2 and 3, which may greatly aid the identification of new therapeutic targets and candidate therapies. To prevent respiratory infections, almost everyone with SMA should get a flu shot every year. Other precautions include staying away from crowds and getting adequate rest and nutrition.
PREVENTION: Preventing spinal muscular atrophy Due to this condition being genetically transferable via recessive genes, spinal muscular atrophy can be prevented by genetic screening techniques, including preconception SMA carrier gene screening.
A 2010 study showed that ultrasound can help doctors tell the difference between subtypes of SMA. More recently, results of a 2023 study revealed that ultrasound imaging of the limbs and respiratory muscles can help assess disease progression in all four types of SMA.
The Spinal Muscular Atrophy (SMA) is no more incurable. With modern medical management techniques, parents can prevent to give rise to the birth of SMA children. Also by updating regularly victims of SMA can win over it like noted scientist Stephan Hawking who lived 76 years with the similar disease ALS. The key solution is to bring high awareness of SMA prevention treatment and skills to live with it to win the world.