How spinal muscular atrophy is diagnosed.

Spinal muscular atrophy

Spinal muscular atrophy, or SMA, is a rare, progressive neuromuscular disease that affects about one in 10.000 newborns are affected (1). It is the most common hereditary disease resulting in death in infancy. Predominantly diagnosed in early childhood. (2,3)

In SMA, nerve cells that control muscle movements – called motor neurons – are damaged, leading to the progressive loss of these cells'. (2) As a result, affected individuals suffer from increasing muscle weakness, the main symptom of SMA, as well as muscle atrophy and paralysis. (4) SMA is more than a disease of motor neurons, meaning it also affects the function of other organs such as the heart and digestive tract.

Cause of SMA

The cause of spinal muscular atrophy is a mutation, d.h. a loss or alteration of the so-called SMN1-gene. This gene forms the blueprint for the protein called "Survival of Motor Neuron" – SMN for short. SMN is important in a wide variety of body cells and plays u.a. plays a critical role in allowing nerve cells to communicate with muscle cells and muscles to function properly. (2) Besides the SMN1-gene, there is a second gene in the human body to produce the SMN protein – the SMN2-Gene. However, the body can only produce about 10% functional SMN protein using this gene. (2)

Does the SMN1-gene because of the gene defect, as is the case in people with SMA, only the SMN2-gene to produce the vital SMN protein. The amount of SMN protein that can be produced depends largely on how many copies of the SMN2-gene a person with SMA has. SMA patients with a higher number of SMN2-Gene copies are usually less affected by the disease. This results in the different types of the disease.

Causes, symptoms, treatment

SMA is an autosomal recessive hereditary disease. This means that only those people who receive a defective SMN protein from both their mother and father will develop the disease SMN1-Inherit gene. If the parents each possess one correct and one defective SMN1-gene copy, and are thus carriers of the SMA hereditary trait, there is a 25% chance that their offspring will develop SMA. (5) Studies indicate that about 1 in 50 people is a carrier. (1)

Knowledge of both the effects of SMN1-The understanding of the genetic defect on the human body, as well as possible treatment approaches for people with SMA, has grown significantly in recent years. This chance seizes

Roche with its research program – aimed at developing new treatment options for people with SMA.

You can find out more about treatment options for SMA here

Inheritance of SMA

What is SMA?

SMA is a hereditary disease that manifests itself – in varying degrees of severity – by progressive muscle atrophy and motor function loss. SMA is caused by a deficiency of the SMN protein. The resultant death of muscle-controlling nerve cells. (2)

Frequency: ca. 1 of 10.000 live births per year. (1)

Type 1 of spinal muscular atrophy

The first signs of SMA type 1 appear in babies before 6 months of age. It occurs during the first month of life. In this severe form, the disease is manifested by a pronounced inability to move. Babies also often find it very difficult to breathe and swallow. If left untreated, babies with SMA never reach important motor milestones in childhood development, such as.B. the ability to sit unassisted, and often die of respiratory failure before reaching the age of two. ( 6)

Every person with SMA is different – the three most common types of the disease

SMA type 2 is referred to when children (usually around 7 to 18 months of age) reach the motor milestone of "sitting without an aid". ( 6) In the case of type 2 disease, motor development is nevertheless severely delayed: Although the children can sit without assistance, they often need support to get into the sitting position. They will never be able to stand or walk. ( 6,7) Life expectancy can also be significantly shortened in this form of SMA compared to healthy individuals. ( 7)

Type 2 of spinal muscular atrophy

People with SMA type 3 are ambulatory at least some of the time in their lives. However, as SMA progresses, they may lose this ability again. ( 9) In SMA type 3, muscle weakness is often more pronounced in the legs than in the arms. ( 6) SMA type 3 usually occurs after the 18. Month of life on. In very rare cases, however, symptoms may not appear until adulthood, in which case we speak of SMA type 4. ( 9) Even if untreated, people with SMA type 3 have a mostly normal life expectancy, unlike SMA types 1 and 2. ( 6)

Type 3 spinal muscular atrophy

The three most common types of SMA and what makes them different

SMA type 1SMA usually appears between 0 and 6 months of age, babies can only lie down but never sit up. (6,8)

SMA type 2 Mostly affects infants between 7 and 18 months of age. You can sit, but never stand. (6)

SMA type 3: SMA most often presents in infants after 18. However, it can also appear for the first time in people in early adulthood. Affected individuals learn to walk, but may lose this ability due to the progression of the disease. (6)

It should be noted that the transitions between the types are fluid. Every SMA patient is different. Depending on the severity, the lack of SMN protein affects the whole body. Is associated with a variety of complications. These include respiratory, cardiovascular, and digestive problems, swallowing difficulties, and lower bone density with increased risk of bone fractures. ( 10,11,13,14) These symptoms indicate that the SMN protein is involved in important basic functions of each body cell. ( 12)

SMA – more than a disease of motor neurons?

SMA is first suspected in the severe type 1 form by observing the characteristic physical abnormalities, v.a. of muscle weakness in legs and arms. Especially in infants, a bell-shaped chest is an important sign of spinal muscular atrophy. (4) Since many SMA patients are young children, the parents play an important role in answering questions relevant to the diagnosis of the disease. Molecular genetic testing provides certainty about the diagnosis of SMA. This means that the doctor takes blood from the person. The cells contained therein are then tested in the laboratory for a defect in the SMN1-gene examined for. Diagnosis as soon as possible and early initiation of causative therapy can best prevent motor neuron loss and significantly improve treatment outcomes for SMA patients.

How is spinal muscular atrophy diagnosed??

A reliable diagnosis of SMA can only be made by genetic testing. For this, blood is taken from the patient to test the blood cells for a defect in the SMN1-gene.

Therapy of SMA

Current treatment options

Since 2017, a first drug therapy for spinal muscular atrophy has been available in Germany. Other therapeutic approaches are under development by various companies. Currently, there are two different approaches. Both aim to increase the amount of functional SMN protein:

via the SMN1 gene: An altered virus produces a defective SMN1-gene into human cells (so-called gene therapy).

via the SMN2 gene: The medication improves the translation of the SMN2-gene into functional SMN protein (so-called "splicing modification").

According to expert recommendations, the treatment of SMA patients requires comprehensive, multidisciplinary medical care due to the complexity of the disease. It is composed of the following eight areas: Nutrition, orthopedics, rehabilitation, pulmonary care, acute care, medication and care of other organs. In addition, rehabilitation measures such as regular physiotherapy can help people with SMA to positively influence the course of the disease. (4)

What are the treatment options for SMA?

A defect-free SMN1-Bringing a gene into the cells (gene therapy)

Better translation of the SMN2-gene into functional SMN protein

Diagnosis of SMA

To date, there is growing evidence that SMN protein deficiency not only affects muscle-controlling neurons, but also interferes with the normal functions of other body cells. (11,15) With this in mind, we at Roche have established a long-term research program on spinal muscular atrophy. The goal is to develop modern treatment options based on the latest findings that can sustainably improve the lives of people with SMA.

Research into SMA continues

For people with spinal muscular atrophy, it's not just about the disease itself. The impact of SMA plays a role in the daily life of patients. of your relatives plays a major role. Since it is a very complex disease, people with SMA need to be treated by an interdisciplinary team of experts, including neurologists and optometrists. Neuropediatricians, pulmonologists, orthopedists, gastroenterologists and physical therapists are supported. It is often a challenge to fit the many, regular examinations into the daily routine. The severe forms of SMA in particular, which occur in early childhood, are an enormous burden for families – especially in everyday life. Feeling alone as a loved one is often an effect of the SMA. All the more important is the exchange with other people with SMA.

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