SMA treatment combo helps boy with type 0 mark third birthday, and walk
Child in Japan given 3 approved drugs plus physical therapy, per case report
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A combination of approved treatments, alongside early physical therapy, was successfully deployed to help treat a boy with spinal muscular atrophy (SMA) type 0 in Japan.
Type 0 is the most severe form of SMA, marked by symptoms that start in the womb prior to birth. Without treatment, babies with SMA type 0 usually die soon after birth.
This child, however, is still alive at more than 3 years old, and while his motor development has been delayed compared with what’s considered typical, as of the latest follow-up he is able to walk, according to clinicians.
The boy’s case was described in a study titled “Outcomes of combination therapy with nusinersen, onasemnogene abeparvovec, and risdiplam over 3.5 years in a patient with prenatally diagnosed spinal muscular atrophy type 0: A case report,” which was published in the journal Brain and Development.
“Our case has shown that even in severe cases such as SMA type 0, where the disease process has already begun, [disease-modifying treatments] can provide beneficial effects if a treatment plan is prepared in advance, with adequate genetic counseling and safe therapeutic intervention,” the researchers wrote.
A genetic disorder, SMA is marked by low levels of SMN, a protein that’s vital for the survival of motor neurons, the nerve cells that control movement. Lacking SMN, motor neurons sicken and die, resulting in SMA symptoms.
Babies with SMA type 0 show signs of disease in the womb
Babies with SMA type 0 characteristically show decreased fetal movement when in the womb, and once born, they typically have profound motor deficits as well as difficulty feeding and breathing.
That was the case for this boy’s older brother, who also had SMA type 0. The brother had required ventilation soon after birth to help him breathe, and while he was able to be kept stable for a time, he ultimately died at age 5 due to a viral infection. The other four siblings were healthy and did not have SMA.
Given this family history, genetic testing was undertaken three months before this child’s birth, revealing that the boy had SMA. After this diagnosis was made, the family and their care team started making preparations to get their newborn treatment as soon as possible.
There are now three disease-modifying treatments widely available for babies with SMA: the injection therapy Spinraza (nusinersen), the one-time gene therapy Zolgensma (onasemnogene abeparvovec-xioi), and the daily therapy Evrysdi (risdiplam). Although they work through different mechanisms, each of therapies is designed to help preserve motor neurons survival by boosting SMN protein levels.
According to the researchers, the infant was born by scheduled cesarean section just after 37 weeks of pregnancy, which is considered full-term. Unlike his brother, at birth he did not show profound motor abnormalities, though testing showed some problems with reflexes and muscle tone.
Treatment, first with Spinraza, started 2 days after birth
Two days after birth, the boy was given an injection of Spinraza, which is administered directly into the spinal canal. Then, slightly more than a week later, the baby underwent treatment with Zolgensma — on the day after he achieved the target body weight.
In this boy’s case, Zolgensma was given “in the shortest possible period in Japan at that time,” the researchers noted. A steroid given the day before the Zolgensma infusion to suppress the immune system was tapered off as scheduled.
In addition to these medications, the baby was also immediately enrolled in physical therapy to supervise and support his motor development.
For the first few months of his life, he showed low muscle tone and muscle weakness on tests, but his motor function scores gradually improved as expected for a developing infant. Then, however, at about 7 months of age, his motor function started worsening, marked particularly by a loss in arm strength.
The family and clinicians decided to start the boy on Evrysdi, while continuing regular physical therapy. After starting Evrysdi, the boy’s motor function gradually improved again.
While his motor development has been delayed relative to normative standards, the child has hit most major early motor milestones, the researchers noted. He was rolling over and sitting up just before age 1; he was able to walk with support just after age 2, and he started walking independently just before his third birthday.
Early intervention with combined [disease-modifying treatments] may be beneficial for patients with severe SMA.
At his latest follow-up, he was able to walk around on his own power for several minutes at a time, had no swallowing or respiratory problems, and could stand up from the floor by grabbing an object, per the report.
However, his deep tendon reflexes were still absent, and the electrical activity resulting from stimulation of nerves of the arm and leg was lower than normal, the team noted.
Still, the researchers reported that levels of the SMN protein showed a remarkable increase at 1 year and 11 months of age, after an initial profound deficit through early infancy.
This boy’s case suggests that the combined use of SMA treatments may be beneficial in cases of severe SMA, though the researchers cautioned that more research is needed.
“Early intervention with combined [disease-modifying treatments] may be beneficial for patients with severe SMA,” the team wrote, noting that “recently introduced … therapies have markedly improved survival and motor outcomes, particularly when initiated presymptomatically or in the early symptomatic stage.”
The scientists stressed, however, that this report details only the case of a single child.
“Since evidence of efficacy and safety of combination therapy is still lacking, great caution should be paid to this treatment strategy, taking the patient’s clinical status into account,” the researchers wrote.
