SMA Gene Therapy

SMA Gene Therapy Now Available

Spinal muscular atrophy is a group of rare genetic disorders that cause patients to lose control and movement of their muscles due to the deterioration of nerve cells in the brain stem and spinal cord.

SMA is a neurological condition and a type of motor neuron disease categorized into 4 main types:

Type 1: The most severe form with age of onset occurring in babies less than 6 months

Type 2: The second most severe type with age of onset occurring in babies between 7 to 18 months

Type 3: The least severe type that affects children, age of onset typically occurs after 18 months

Type 4: Generally a mild form of SMA that only affects adults

Spinal muscular atrophy (SMA) causes the muscles to waste away and become weak. This deterioration of the muscles can lead to difficulty control head movements, standing, walking, and even in some cases, it may even lead to issues breathing and swallowing.

According to the Genetics Home Reference SMA affects between 8000-10,000 people worldwide, and whilst some types of SMA may be present at birth, others develop later in life.

There is currently no cure for SMA, however medications such as nusinersen (Spinraza) and onasemnogene abeparvovec-xioi (Zolgensma) gene therapy, have been shown to slow down progress.

Different Types of SMA

SMA Type 1

Type 1, also known as Werdnig-Hoffmann disease, is a very serious form of the condition that typically develops after 6 months. Type 1 causes breathing problems, which can become fatal within a year if left untreated.

Symptoms include twitching, muscle weakness, a loss of ability to move limbs, trouble eating, and, then over time, it can also lead to the curvature of the spine.

Type 1 can be detected prior to birth typically noticed by the fetus low levels of movement during the later stages of pregnancy. In cases where the condition is not diagnosed prior to birth it will then likely become evident after just a few months.

Whilst there is no current cure for Type 1 SMA, newer treatments such as disease modifying therapies (DMTs), are now enabling some children to sit and/or walk.

SMA Type 2

Type 2 SMA is a less severe form of SMA than type 1. It often appears between the ages of 6-18 months, and whilst children with the condition may be able to learn to sit, its likely they will never be able to walk or stand, and without treatment it’s also possible for the patient to even lose their ability to sit.

Life expectancy of SMA 2 largely depends on whether or not related breathing problems are also present. Those without breathing issues are likely to have a longer life expectancy; however, most people with the condition survive into adolescence or young adulthood.

Again, whilst there is no cure for SMA Type 2, treatment with DMTs has been shown to help reduce symptoms.

SMA Type 3

Also known as Kugelberg-Welander disease, SMA Type 3 typically appears after 18 months. It can lead to the development of scoliosis (side ways curvature of the spine), contractures (tightening of the muscles and/or tendons), which can lead to joint pain and problems with coordinated movement.

Type 3 is less severe than Type 2, and as a result most patients will be able to walk, however it is common to develop an unusual gait, and some may have troubles running, climbing steps or getting up from a chair. In some cases it can also cause slight tremors in the hand.

Another complication that may arise from SMA Type 3 is a higher risk of respiratory infections, however with the correct treatment, it is possible for patients with SMA type 3 to live relatively normal lives, with a normal life expectancy.

Type 4 SMA / Adult SMA

This mild type of SMA is known to only affect adults over the age of 21, and generally only leads to mild symptoms of muscle weakness, typically in the muscles around center mass (moderate proximal weakness).

Causes of SMA

SMA occurs when mutations to the survival motor neuron 1 (SMN1) and SMN2 cause motor neurons in the spinal cord and the brain to malfunction. Since motor neurons are the nerve cells responsible for movement, and the SMN1 and SMN2 genes are responsible for passing instructions to create the protein necessary for these motor neurons to function, when changes to these gene occur it can interfere with this process and lead to the development of SMA. For example, a problem SMN1 will lead to SMA, while issues with SMN2 will affect the type and severity.

It’s reported that 1 in every 40-60 people have the genetic problem that could lead to SMA, however for the condition to be inherited both parents must have this mutated gene. Even then it’s estimated that only 1 in every 4 children will e end up inheriting it.

SMA Gene Therapy Now Available 1

Diagnosis of SMA

Diagnosis is usually carried out once a parent or caregiver starts to notice the telltale lack of movement in a fetus or child with SMA.

At this point, a doctor will perform a medical history and family history check and a physical exam.

This exam will look for signs that the muscles have become flaccid, floppy, or weak in any other way. It will also check for tongue twitching. The physician will also test the patient’s deep tendon reflexes.

Additional tests used to diagnose SMA may include:

Treatments for SMA

As previously noted, there is currently no cure for any type of SMA, however, there are several medications and forms of therapies that can lessen symptoms and in less severe cases, promises regular life expectancy.


Medications for SMA

One type of medication the can reduce the severity of symptoms is DMTs (disease modifying therapies). By reducing the severity of symptoms patients can improve their outlook and in many cases lead a relatively normal lifestyle. Two FDA approved medications are available for SMA, these include:


Can treat all types of SMA by reducing muscle weakness, however its effectiveness is known to vary between patients. It is typically administered in 4 initial doses over 2 months; with follow doses every 4 months. Spinraza works utilizing a class of drugs known as antisense oligonucleotides (ASOs), which target the underlying problem by promoting the production of RNA.


This is a type of gene therapy used to treat children under the age of 2. It is administered in a single dose, which adds new copies of healthy genes to replace the broken/defective ones causing the condition.

ZOLGENSMA gene therapy for the treatment of SMA in children less than 2 years old was approved by the FDA in 2019 and is available by prescription. The treatment has been shown to be highly effective with 100% of patients increasing their CHOP-INTEND points by at least four, while just 71% of those who took Nusinersen increased in their score.

Assisted Devices and Therapy

In addition to the medications available to treat SMA, there are also a number of assisted devices and therapies that can help improve the lives of those with the condition. Assistive technology can include powered wheelchairs, modified access to certain areas such the computer or bathroom, ventilators to assist with breathing, as well as other walking aids that can help patients get around.

Physical Therapy

Perhaps the most popular type of therapy administered to those with SMA, therapies typically include wheelchair sports and water therapy.

Outlook for SMA

Outlook and life expectancy for those with SMA can vary greatly depending on the severity of the symptoms. Infants are often at most risk, and can develop respiratory diseases that can sometimes be fatal, especially when left untreated.

However, those with milder forms of SMA often live as long as those without SMA, although some may need medical aid, and support will typically be required along the way.

Unfortunately it is still not possible to prevent SMA, however modern medications, and treatments such as physical therapy, as well as other strategies can all work together to help make a person with SMA live a long and full active life.

Furthermore, the search for a cure to this rare has not rested. Researchers learn more about SMA everyday with the hopes of developing new and experimental treatment that show true promise in treating, or even preventing, and curing the rare disease the not too distance future.

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