Remarkable Breakthrough in Spinal Muscular Atrophy

Happy toddler eating breakfast with hands up

We’ve all mused about how our children will never understand what it was like to use a rotary dial phone or to wait for your favorite song to play on an 8-track tape. Technology just moves so quickly. Chances are, the newest generation may feel that way about gene therapy.

Dr. Samiah Al-Zaidy, MD, presented the latest evidence for the potential of gene therapy at the April 2018 meeting of the American Association of Neurology in Los Angeles. She discussed a recent trial for young children with Spinal Muscular Atrophy Type 1 (SMA 1). This Phase 1 trial was designed to look at the safety of the treatment, as Phase 1 trials do. But the outcomes were impossible to ignore.

Over ninety percent of the time, the outcome for SMA1 without treatment is death before the second birthday. These children do not meet developmental milestones, and their health declines rapidly to include ventilator dependence in the later stages of the disease.

But for the 15 children treated with gene therapy, the course of disease is quite different. They are all alive and not dependent on a ventilator. This is more than 24 months after treatment.

Happy toddler eating breakfast with hands up

Researchers at Nationwide Children’s Hospital in Columbus, OH, studied the effects of replacement of the mutated gene encoding for survival motor neuron (SMN) 1. They achieved this by administering a single dose of intravenous adenovirus vector gene therapy encoding the missing SMN protein. Three of the patients received a minimally effective dose, while the remaining patients received high doses.

The primary outcome in the study, as mentioned, was safety. Two patients had severe elevations in liver transaminases at about three weeks post-dosage, but that was controlled with prednisolone with no long-term consequences. There were no other severe adverse events.

The secondary outcome was time to death or permanent ventilator assistance. Initial results from August 2017, 20 months post-dosage, were published in the New England Journal of Medicine in November. The final results at 24 months post-dosage were reported at the AAN meeting by Dr. Al-Zaidy. All children remain alive, and none require ventilator assistance. Some have achieved milestones unexpected for children with SMA1, including sitting up with assistance, sitting unassisted for 30 seconds, and even walking. None of the children have lost milestones achieved previously during the study.

Dr. Al-Zaidy reports that after the encouraging final follow-up at 24 months post-dosage, a long-term follow-up study is planned to monitor progress in these children for 15 years.

It is difficult to overstate how life changing the remarkable results of this treatment will be for children born with SMA1 and their parents. It also offers hope for the many who are affected by genetic disease of all kinds. Let’s hope these kids grow up and view the pre-gene therapy days in the same way they’ll view the days before streaming video—as part of the dark ages.

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