Texas Children’s is among the first pediatric hospitals in the nation to offer the new FDA-approved treatment for spinal muscular atrophy (SMA), a rare genetic disease affecting muscle strength and movement, and is among the leading genetic causes of death in infants.
About one in 10,000 babies are born worldwide with SMA. This inherited condition is caused by a mutation in a gene (SMN1) that produces Survival Motor Neuron (SMN) protein, which is essential to the normal function and survival of motor neurons. Motor neurons are nerves that control skeletal muscles. If motor neurons cannot function properly or are dead, it can lead to progressive debilitating weakness of all muscles in the body, including those important for breathing. Humans have two closely related versions of the SMN gene, SMN1 and SMN2.
Normally, SMN1 produces a fully functional SMN protein 100 percent of the time as the motor nerve cell “reads” the gene code and splices the amino acids together to make the protein. However, a “clumsy reading” defect in the SMN2 gene leaves out a critical amino acid (a splicing defect), which means this gene produces normal SMN protein only 10 percent of the time. Thus, motor nerve cells totally depend on SMN1 since it is the “workhorse” that produces normal SMN protein.
A new DNA-based antisense oligonucleotide therapy corrects the “clumsy reading” (splicing defect) of the SMN2 gene so it produces the SMN protein nearly 100 percent of the time that the motor nerve cell uses that code. Anti-sensense oligonucleotides are small pieces of synthetic genetic material that can fix errors during production of proteins from their starting material, DNA. This drug is marketed as Spinraza (nusinersen).
This therapy administered by injection into the spinal canal through a lumbar puncture procedure, so that the drug reaches the cerebrospinal fluid directly and can then have access to the motor nerve cells in the spinal cord. The drug cannot efficiently reach the spinal fluid or spinal cord through the bloodstream. Initially, patients receive four doses in the first two months followed by booster doses every four months for rest of their life.
“The good news is that in the clinical trials, SMA type 1 patients, who are among the most severely affected from birth, showed significant benefits in motor skills and breathing over placebo control patients,” said Dr. Timothy Lotze, neurologist and clinical medical director of the Muscular Dystrophy Association Care Center at Texas Children’s, where SMA patients are treated. “These infants, who would otherwise not be expected to even lift their heads, were rolling over, sitting up, and some even standing on their own. Many of the treated infants did not need breathing support, which is truly amazing for patients with this disease.”
In the clinical trials, potential side effects associated with this treatment were generally mild and included headaches after lumbar puncture. Since this is a medically fragile population consisting mainly of young children, some of who may have associated breathing difficulties, scoliosis and osteoporosis, there must be careful consideration as to how and where the lumbar puncture will be performed, as some of them may require assistance from interventional radiology.
“Until Sprinraza was developed, we could not offer SMA patients any treatment options, other than supportive care,” Lotze said. “For the first time, this drug offers the possibility of stopping, recovering and perhaps, even preventing SMA symptoms. It is truly a “game-changer” for these patients.”