Atrofia muscular espinal

La atrofia muscular espinal (AME) se refiere a un grupo de enfermedades hereditarias que pueden dañar y destruir células nerviosas especializadas en el cerebro y la médula espinal (neuronas motoras). Las neuronas motoras controlan el movimiento de los brazos, las piernas, la cara, el pecho, la garganta y la lengua, así como la actividad de los músculos esqueléticos, como hablar, caminar, tragar y respirar.

The most common form of spinal muscular atrophy (SMA) is caused by a mutated or missing gene known as the survival motor neuron gene 1 (SMN1), which is typically responsible for the production of a protein essential to motor neurons. There are four types of this form of SMA:

1. Type l (also known as Werdnig-Hoffman disease or infantile-onset SMA) is usually evident before six months of age. The most severely affected children will have reduced movement and chronic shortening of muscles or tendons (contractures). Other children may have symptoms including reduced muscle tone, lack of tendon reflexes, twitching, skeletal abnormalities, and problems with swallowing and feeding. Without treatment, many affected children die before age two.
2. SMA Type ll is usually first noticed between six and 18 months of age. Children can sit without support but are unable to stand or walk without help. Children may also have respiratory difficulties. Life expectancy is reduced, but most individuals live into adolescence or young adulthood.
3. SMA Type lll (also known as Kugelberg-Welander disease) is seen after age 18 months. Children can walk independently but may have difficulty doing so or when 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 an average lifespan.
4. SMA Type IV develops after 21 years of age, with mild to moderate leg muscle weakness and other symptoms.

The most common form of SMA is caused by a mutated or missing gene known as the survival motor neuron gene 1 (SMN1). The SMN1 gene is located on chromosome 5q and produces the survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons.

People living with SMA have insufficient levels of the SMN protein, which leads to loss of motor neurons in the spinal cord and causes weakness and wasting of the skeletal muscles. The weakness is often more severe in the trunk (chest) and upper leg and arm muscles than in muscles of the hands and feet.

Many types of spinal muscular atrophy are caused by changes in the same genes. Less common SMA forms are caused by changes in other genes including the:

• Gen VAPB en el cromosoma 20
• Gen DYNC1H1 en el cromosoma 14
• BICD2 gene on chromosome 9
• UBA1 gene on the X chromosome

Except in rare cases, spinal muscular atrophy (SMA) is inherited in an autosomal recessive manner, meaning that the affected individual has two mutated genes, often inheriting one from each parent. Those who carry only one mutated gene are carriers of the disease who will not have any symptoms.

A blood test is available to look for mutations or deletions of the SMN1 gene. This test identifies at least 95 percent of SMA Types I, II and III, and also may reveal if a person is a carrier. If the SMN1 gene is not found to be problematic or the individual’s history and examination are not typical of SMA, other diagnostic tests may include:

• Electromyography to record the electrical activity of the muscles during contraction and at rest
• Nerve conduction velocity studies to measure the nerve’s ability to send an electrical signal
• Biopsia muscular para diagnosticar muchos trastornos neuromusculares
• Other blood tests

Las personas con atrofia muscular espinal (AME) presentan niveles insuficientes de la proteína SMN, lo que provoca la pérdida de neuronas motoras en la médula espinal y causa debilidad y atrofia de los músculos esqueléticos. La debilidad suele ser más grave en el tronco (pecho) y los músculos de los brazos y las piernas que en los de las manos y los pies. Además de la debilidad y la disminución del tono muscular, los síntomas incluyen movilidad reducida, problemas respiratorios, escoliosis (curvatura de la columna vertebral), retraso en el desarrollo de la motricidad gruesa, dificultades para comer y tragar, y movimientos espontáneos de la lengua.

A blood test is available to look for mutations or deletions of the SMN1 gene. This test identifies at least 95 percent of SMA Types I, II and III, and also may reveal if a person is a carrier. If the SMN1 gene is not found to be problematic or the individual's history and examination are not typical of SMA, other diagnostic tests may include:

• Electromyography to record the electrical activity of the muscles during contraction and at rest
• Nerve conduction velocity studies to measure the nerve's ability to send an electrical signal
• Biopsia muscular para diagnosticar muchos trastornos neuromusculares
• Other blood tests

There is no complete cure for spinal muscular atrophy (SMA). Treatment consists of managing the symptoms and preventing complications.

Medicamentos:

• The U.S. Food and Drug Administration (FDA) approved nusinersen (Spinraza™) as the first drug approved to treat children and adults with SMA. The drug is designed to increase production of the SMN protein, which is critical for the maintenance of motor neurons.
• The FDA approved onasemnogene abeparovec-xioi (Zolgensma™) gene therapy for children less than two 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 survival.
• The FDA approved the orally administered drug risdiplam (Evrysdi) to treat patients aged 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 contractures, increase range of motion and keep circulation flowing. Some individuals require additional therapy for speech and swallowing difficulties. Assistive devices such as supports or braces, orthotics, speech synthesizers and wheelchairs may be helpful to improve functional independence.

Proper nutrition and calories are essential to maintaining weight and strength, while avoiding prolonged fasting. People who cannot chew or swallow may require insertion of a feeding tube. Noninvasive ventilation at night can improve breathing during sleep, and some individuals also may require assisted ventilation during the day due to muscle weakness in the neck, throat and chest.

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 contractures, increase range of motion and keep circulation flowing. Some individuals require additional therapy for speech and swallowing difficulties. Assistive devices such as supports or braces, orthotics, speech synthesizers and wheelchairs may be helpful to improve functional independence.

Proper nutrition and calories are essential to maintaining weight and strength, while avoiding prolonged fasting. People who cannot chew or swallow may require insertion of a feeding tube. Noninvasive ventilation at night can improve breathing during sleep, and some individuals also may require assisted ventilation during the day due to muscle weakness in the neck, throat and chest.

Consider participating in a clinical trial so clinicians and scientists can learn more about SMA. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat or prevent disease.

Se necesitan voluntarios (tanto sanos o con alguna afección o enfermedad), de todas las edades, sexos, razas y etnias para garantizar que los resultados del ensayo sean relevantes para la mayor cantidad posible de personas, y que los tratamientos sean seguros y eficaces para todo aquel que los necesite.

For information about participating in clinical research, visit NIH Clinical Research Trials and You. Learn about clinical trials currently looking for people with SMA at Clinicaltrals.gov, a searchable database of current and past federal and private clinical studies.