Treatment is not a cure for patients with SMA

Lim (left) and Yap, seen here helping their younger son and SMA patient Branden stretch his muscles, stress that treatment for this rare disease is not a cure and that parents need to be prepared to continue providing care for their child. — ART CHEN/The Star

Where once parents of spinal muscular atrophy (SMA) patients asked her about what is the best care they can give their child, now they will first ask about treatment.

As the co-founder of the SMA non-profit organisation WeCareJourney and mother to a 12-year-old son with the rare disease, Yap Sook Yee is used to helping and supporting her fellow parents who have been told that their child has SMA.

She says: “When parents hear there’s a drug, they think everything will be cured.”

However, this is not the case.

Assuming that their child is able to access one of the three currently-available treatments for SMA, it is crucial to note that certain complications due to the condition might still occur.

In SMA, a child inherits two defective copies of the recessive SMN1 gene.

This gene is in charge of producing the majority of a protein called survival motor neuron (SMN) in the body.

Functional versions of this protein are only produced in small amounts by the SMN2 genes, which are the target of two of the treatments for SMA.

Without sufficient SMN protein, the body’s motor neurons will start to die, impacting the patient’s capability for both voluntary and involuntary muscle movement.

“What treatment does is it stops SMA – certain complications will still occur, e.g. scoliosis and lung infections like pneumonia.

“You still have to do a lot of physiotherapy and all that – the care continues,” says Yap.

In addition, the patient is unlikely to recover whatever motor function they have already lost prior to treatment.

Says her husband and WeCareJourney co-founder Edmund Lim: “If you’re looking at a child or an adult who already has a lot of motor neuron loss, the treatments will not bring back the motor neurons.

“It’s like cutting off a leg – it will not grow back, but if you are bleeding, it can stop the bleeding.

“So people mistake that if you stop the bleeding, the leg will grow back – no, it doesn’t!”

Motor neurons are among the types of cells that have very limited regenerative capabilities, so once they die, the body is unable to replace them.

He adds: “So many families, they have expectations of normalcy with treatment, but the patient will be frozen at their current level of functioning.

“They may get a bit of a bump-up because the disease is stabilised, but it will effectively be what it is.”

Currently, the genetic therapy onasemnogene abeparvovec-xioi offers the closest thing to a cure for SMA.

But even then, it comes with the warning that the patient still has SMA and may still experience symptoms like difficulty in breathing or swallowing, or muscle weakness, after the one-time treatment.

This therapy replaces one of the defective SMN1 genes with a working copy, thus enabling the body to produce sufficient levels of SMN protein.

A phase 3 clinical trial did show that babies who have SMA, developed similarly to healthy babies by 18 months of age when given the therapy before they develop any symptoms.

The study, which was published in the journal Nature Medicine last June (2022), had identified the babies via newborn screening.

However, most SMA patients face many hurdles in even getting diagnosed and are likely to have some level of motor neuron loss by the time they are identified as having SMA.

With the issue of financing, their condition is likely to have deteriorated further if and when they are able to get treated.

Therefore, Yap says: “Parents have to be given really good counselling at the start when the doctors are telling them what the treatment can do for their child.

“Not straightaway give them hope that this is a cure.”

Preventive efforts and care to keep their child as well as possible and functioning optimally are likely to still be needed, even with treatment.

This article is part of the second package of a short series written as part of the US National Press Foundation’s 2022 Covering Rare Diseases: Journalism Fellowship & Global Reporting Grant. The next one will be published this Sunday (Jan 8, 2023) in StarHealth.