Two toddlers ‘miraculously’ regain abilities to stand and sit up after new therapy to treat most deadly genetic disease in infants

Spinal muscular atrophy kills more infants than any other genetic disease

Both of Danyelle Sun’s children suffer from a genetic disorder that has robbed them of the physical strength to even stand on their own.

Ruby, age six, and Landon, age three, have spinal muscular atrophy (SMA), which kills more infants than any other genetic disorder.

But since they began getting treatments of the new drug, Spinraza, in July, Ruby and Landon have already begun to make remarkable progress.

This week, the New England Journal of Medicine (NEJM) published promising results from studies on the same drug Ruby and Landon are taking and a new gene therapy that could infants that often die of SMA within the first years of life.

Ruby and Landon will have to have Spinraza injections for the rest of their lives, but a gene therapy in clinical trials could stop the disease in its tracks with just one shot.

SMA affects about one in every 10,000 infants born, and it kills more infants than any other genetic disease, and those that do survive face developmental delays, limited mobility, and many will need lifelong care.

About one in every 50 Americans are genetic carriers of SMA, but the because the gene is recessive, there are rarely cases in a family’s medical history. There are four types of the diseases. The worst and most common is type one, which affects babies from birth.

Because SMA causes muscle atrophy, infants born with it – one of the criteria of type 1 – often struggle to swallow and even breathe, impairments that kill many.

The other three types of SMA are less common, come on later – either between six and 18 months, after 18 months, or, in very rare cases, in adulthood – and are less severe, but still very limiting.

She’ll see pictures of herself and be really confused. She’ll say ‘that was me? I could stand up?’
Danyelle Sun, describing six-year-old Ruby

Ruby Sun was just over a year old and had just started walking across the living room when the falls began. As she continued to try to walk, her mother noticed that Ruby’s falls and weakness didn’t look like normal toddler clumsiness.

By the time the neurologist diagnosed Ruby with Type 3 SMA, she was hardly walking, and couldn’t stand up on her own. A month later, Danyelle watched her daughter take what she thought would be her last steps.

Ruby has primarily used a wheelchair to get around ever since.

Landon, Danyelle’s second child with her husband Terence, has exactly the same genetic misconfiguration for SMA as his older sister.

Both children are missing a gene that codes for the making of the survival motor neuron protein: SMN1.

While both have the so-called ‘back up’ gene, SMN2, which ‘produces just a little bit of useful protein, and can kind of make up for SMN1′ it does not offset it entirely, says Megan Lenz, director of marketing and communications for Cure SMA.

Now six years old, Ruby excels in first grade, and her public school outside Milwaukee, Wisconsin, provides physical and occupational therapy. But while she enjoys her equine and swimming therapy, which help her to stay active and build strength, she has not been able to stand or walk.

Landon is now three. Danyelle says ‘he developed pretty typically until around 10 months, then one day he just stopped bearing weight on his legs. After that, he would just fold his legs and tumble down.’

‘With SMA, everyone is so different. Even with two kids with the same gene, they’re very different,’ Danyelle says. ‘You don’t notice small changes, from month to month, until you look up six months, a year later.’

The Sun family doesn’t let SMA slow them down. Danyelle (left) and her husband Terence (right) took Ruby, six (left of center), and Landon, three (right of center), to Epcot this year

Even Ruby has been surprised by her own deterioration, Danyelle says. ‘She’ll see pictures of herself and be really confused. She’ll say “that was me? I could stand up?”’

Babies with SMA type 1 appear limp and have trouble controlling their heads and necks.

Children and adults with other types, like Ruby and Landon have full cognitive abilities, but the disease makes them progressively weaker physically.

Until now, there have been no known treatments or cures for SMA. For babies with type 1, their best hope for survival depends on being on a breathing machine, permanently.

At 18-months-old (pictured) Ruby could stand on her own. Soon after this photo was taken, Ruby’s AMS progressed and she became wheelchair bound. But, with a new treatment, Ruby may stand again soon
The new gene therapy, made by Avexis, recently went through a phase one clinical trial, the results of which were published in this month’s NEJM.

It uses a modified virus to deliver the healthy version of the gene to infants with SMA, delivered through a one-time shot into a vein to replace the missing SMN1 gene.

The 15 babies from the trial are all alive, and at 20 months, none of them had been placed on breathing machines.

The average life expectancy of an infant with type 1 SMA is under two years, and only about eight percent of infants typically make it to 20 months alive and without assisted ventilation.

The success of this trial is promising for the next stage of the drug’s pathway to market, which will determine if Avexis will file for FDA-approval of the treatment.

In the meantime, Spinraza is approved for use in both children and adults and new data from one of its trials – also published this week in the NEJM – suggests that the drug is not just preventing the SMA from progressing, but allowing children with the disease to make unprecedented motor ability gains.

All of the trial subjects were given their first doses of Spinraza as infants. Spinraza is given in four loading doses in quick succession, and patients will have to get a lower-dose maintenance injection once every four months, for the rest of their lives.

Spinraza provides a fix to the back-up gene, SMN2, so that it can produce more of the missing protein.

After their first Spinraza injections, 51 percent of the infants in the study had had reached motor developmental milestones. In the control group of infants that did not receive the drug, none made any motor gains.

The drug also reduced the odds that an infant with SMA would die by nearly half.

Landon was able to sit up and swing by himself just three weeks after getting his first Spinraza injection in July
‘Often, individuals with SMA progressively lose functions as the disease progresses, so this is something that our community looks very strongly at,’ says Lenz.

For Danyelle’s children, the drug has been an inspiration.

Since she and Landon got their first injections (placed into the lower spine for children and adults, rather than intravenously in babies) in July, Ruby has begun on her knees at home, and is far less fatigued, her mother says. She is even walking in the pool.

Landon, who had to be surround by pillows when he was sitting up in case he fell over, is now sitting up without falling, has much better torso control, can reach for things, and, just this week, started kneeling again, Danyelle says.

They’re very proud, we joke around the house, whenever they do something really impressive, or exciting, they’ll say “hashtag Spinraza goals!”’ Danyelle laughs.

With drugs as new as Spinraza – and even more so for the experimental gene therapy – there is no way to set expectations for how Landon and Ruby will continue to progress, and ‘doctors don’t tell us what is going to happen,’ Danyelle says.

‘There’s no clear pathway, but I have a great sense of hope and a lot of optimism that maybe they could get there; for my personal expectations, I think Ruby could possibly get to the point of at least walking with a walker,’ she says.



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