By Lenika De Simone, Vera Shively and the Genetic Counseling Team at Lurie Children’s
There are many neuromuscular disorders, including SMA. Depending on the type of disorder, symptoms may appear during infancy, childhood, as well as the adult years. Research is leading to a better understanding of the genetic basis for some of these disorders and new approaches to treatment. This is the case for SMA.
SMA is a progressive neuromuscular disorder that involves nerve cells (neurons) and the muscles they control. SMA leads to a loss of motor neurons in the spinal cord. Motor neurons are important because they send messages from the brain to muscles that direct much of the movement in our bodies. When muscles do not receive these messages, they become weak and waste away.
SMA is classified into 4 different types, 1 to 4. These are based on the child’s age when symptoms first appear (onset) and the severity of symptoms. Type 1 is the most severe form, and often appears before an infant is 6 months old. Children with SMA type 1 are unable to sit up, walk, or eat on their own. The child’s breathing can also be affected.
We know that SMA is caused by a genetic change (sometimes called a mutation) in the survival motor neuron 1 gene (SMN1). The SMN1 gene carries the instructions to make the SMN protein, which is important for motor neurons to work properly. Without SMN protein, the motor neurons disappear or lose their function. Knowing the specific genetic cause of SMA has been key in the development of the new treatments for the disorder.
There are two FDA-approved treatments for SMA. The first is called nusinersen (Spinraza®), and it is an antisense oligonucleotide (ASO) therapy. The ASOs in nusinersen work by helping the body create SMN protein to keep motor neurons healthy. Nusinersen is injected into the cerebrospinal fluid that bathes the brain and spinal cord. These injections must be performed by specially trained healthcare providers, and are done on a regular, ongoing basis. Nusinersen is not suitable for all patients with SMA, and it may not benefit all patients who try this drug.
The second treatment for SMA is a gene enhancing-therapy called AVXS-101 (Zolgensma®). Gene therapies are meant to be one-time treatments that insert genetic material into the body to compensate for the non-working gene. AVXS-101 was designed to deliver a working copy of the SMN1 gene to motor neuron cells so they can produce SMN protein and continue delivering messages to muscles. The drug is given through an intravenous (IV) infusion. In 2019 it was approved for children up to the age of two years. Early reports have shown promising results. However, its extraordinary high price and a lack of access to the drug have caused much debate.
Newborn screening is a state public health service. When the baby is at least 1 day old, a small blood sample is collected from the baby’s heel and is used to screen for rare but serious medical conditions. These are conditions where early diagnosis and treatment can have a significant positive impact on the child’s health. While there is a national recommended set of conditions to screen, each state determines what conditions to add to their own panel. Given the new treatments available for SMA, many states have supported its addition to the newborn screening panel. The earlier an infant is diagnosed with SMA, the more likely one of the two treatments available will benefit the child. For this reason, Illinois will begin statewide testing for SMA in June 2020.
Parents are notified by their pediatrician or birth hospital staff that their baby has a positive newborn screen. The family will then be referred to specialists for further evaluation. The Neuromuscular and Genetic Teams at Lurie Children’s will examine the baby, explain the newborn screening test results, arrange follow-up diagnostic testing, provide guidance and counseling to parents, and coordinate any necessary treatment and medical care.
The new treatments for SMA provide hope for a healthier child, yet families experience much uncertainty about the future. Several of the resources listed below provide support, advocacy and connect families affected by SMA.