Administration of Spinraza (nusinersen) directly into the spinal canal is feasible and well-tolerated by adults with spinal muscular atrophy (SMA) type 2 or 3. Still, such treatment can be challenging for SMA type 2 patients and those who have had spinal fusion, a study shows.
The study, “Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy,” was published in the journal Therapeutic Advances in Neurological Disorders.
SMA is caused by mutations in the SMN1 gene, which leads to reduced production of the SMN protein. While humans have a second survival motor neuron gene (SMN2) capable of producing SMN, a slight difference in its DNA sequence makes 90 percent of the resulting SMN protein shorter and nonfunctional.
Spinraza is an antisense oligonucleotide (ASO) developed by Biogen to overcome the damaging effects of SMN1 gene mutations known to cause SMA. The treatment increases the ability of the SMN2 gene to produce full-length SMN protein.
In December 2016, Spinraza became the first approved treatment indicated for almost all types of SMA in the United States. This was followed by approval in other countries, including Australia, Brazil, Japan, Switzerland, South Korea, Canada, Chile, and several other countries in Europe.
Compelling evidence exists demonstrating Spinraza’s potential to improve motor development, motor function, and survival of infants and children with SMA type 1 or type 2.
Spinraza is currently administered through an injection into the cerebrospinal fluid (the fluid in the spine) — a procedure called intrathecal injection — every four months throughout a patient’s life. Intrathecal injection allows Spinraza to easily reach the central nervous system (spinal cord and brain) that is mainly affected by SMA.
However, this type of administration presents safety and accessibility challenges in many SMA patients with spine deformities.
Bone grafts or bone-like materials are placed between the vertebrae and fixed with rods and screws while the fusion heals. This type of surgery is for patients who can no longer walk and are over age 10, as fusion prevents further growth of the spine.
Intrathecal administration of Spinraza can also cause complications and there is currently little information on the treatment’s safety and activity in adult patients.
To address this matter, a German team of researchers and clinicians evaluated the safety and tolerability of intrathecal administration of Spinraza in adults with SMA.
The study enrolled 28 patients, nine of whom had SMA type 2 and 19 who had SMA type 3. Patients received their first injection at the mean age of 35.8 years. About half of the SMA type 3 patients were able to walk when they started the treatment, whereas no SMA type 2 patients could.
The team successfully administrated Spinraza in 26 patients, who received four or more intrathecal injections. One patient with SMA type 2 did not receive the initial injection due to failure of the computed tomography (CT)-guided lumbar puncture protocol, and a second patient received the initial dose just before the study ended.
Overall, the team performed 65 conventional lumbar punctures in 14 patients with SMA type 3, all of which were successful. CT-guided lumbar punctures were performed in nine patients who had SMA type 2 and in two patients who had SMA type 3; these were successful in 97% and 100% of cases.
“With the exception of two cases, all injections were performed by the method originally intended,” researchers wrote. “A well-tolerated injection of [Spinraza] succeeded in all but one patient, independent of age, type of SMA, and the presence of a [spinal deformity].”
During the study, 81.5% of patients experienced at least one adverse event, the most common being persistent headache, back pain, nausea, constipation, and dizziness. No serious treatment-related adverse effects were reported.
“Our data provide evidence for the feasibility and safety of intrathecal treatment with nusinersen in adults with SMA type 2 and type 3 [in a] ‘real life’ clinical experience,” researchers wrote.
The team said that for patients with SMA type 3 and advanced scoliosis, the use of fluoroscopy-assisted lumbar punctures may help achieve successful Spinraza treatment. For SMA type 2 patients and for those who have had spinal fusion, CT-guided lumbar puncture may represent the best approach to avoid adverse events, they suggested.
That team believes that “detailed patient information, consideration of individual patient’s resources, and interdisciplinary cooperation between neurologists and neuroradiologists are required” to achieve the best outcome of Spinraza treatment in adult SMA patients.