Q1. What is a good resource to learn about the Genetics and treatments available for Spinal Muscular Atrophy (SMA)?

The following is a concise article from the Irish Medical Journal titled New Frontiers in the Treatment of Spinal Muscular Atrophy posted by Dr. Declan O’Rourke who is the lead expert in SMA in Ireland and is currently treating Theo.

It is a recessively inherited genetic condition, which means that both parents need to be carriers of the mutated SMN1 gene and then the child has a 1 in 4 chance of having the disease. Without this gene which produces a downstream protein called survival motor neuron protein, anterior motor neuron cells will die over time. The backup SMN2 gene dictates the severity of the disease, with SMA type 1 being the most severe* and correlates with 2 backup copies of SMN2 gene typically (~70-80% of cases of SMA type 1), but sometimes can be 3 copies which has a slightly less sever presentation. 2 copies SMA type 1 will more likely mean the patient will require ventilatory and feeding support.

Unlike a few years ago in Ireland, SMA is now a treatable condition with recent advances in genetic therapies. The key to better outcomes in patients is reliant on early diagnosis and early treatment. This is because the disease is progressive and motor neuron cells that die due to a lack of the survival protein will not recover. The key is to stop the progress of motor neuron cells dying by increasing the survival motor neuron protein they require to thrive.

The other difficulty with SMA currently is that the current cutting edge treatments are enourmously expensive and in Ireland the gene therapy Theo needs is not available to him and we cannot cover the cost and it is not reimbursed to families. It is reimbursed in other countries such as the UK and Germany.

Two breakthrough gene-targeted treatments for spinal muscular atrophy: challenges remain.
The research paper above details current treaments for SMA and recent advances in gene therapy and antisense oligonucleotide medicines (nusinersen) have changed the outcomes of thsi disease.

* SMA type 0 cases are very rarely diagnosed, it is an even more severe than type 1 and the infants generally do not survive if they are born.

Q2. How is Theo doing today ?

Theo is an amazingly happy and content baby. Thankfully SMA babies are cognitively normal. He was born April 29th 2021, and started Spinraza therapy on 19th of August at exactly 17 weeks old. He was symptomatic at treatment and had severe hypotonia (low muscle tone). At the time of writing Theo is nearing 5 months old and can not lift his head himself and is still floppy when you hold him. He has the ability to lift his arms but not much so to lift his elbows veritcally. His distal muscles work better such as feet and hands but as expected with SMA the have less muscle in proximal (close to body) muscles. We are hopeful to see some progress after his 4th dose of the Spinraza loading phase particularly in these regards to proximal mucles and head control when sitting. Luckily he can hold his head when we hold him but not very strong moving side to side.

He has difficulty swallowing so he has a nasogastric tube to prevent any aspirations to his lungs. He currently has no ventilatory support but will likely need the in the future and that he will not get better from a feeding/swallowing perspective. This is unless he gets Zolgensma gene therapy treatment which has more evidence suggesting improvements in these vital capacities. This is because Zolgensma treatment will affect more cells in the body because of it’s systemic nature, and deliver the gene and hence the protein where it’s needed more effectively.

We have to do everything in our capacity to get Theo the best treatment possible to live a good life. This will mean getting him the Zolgensma treatment in Ireland or France. With this gene therapy, there is reasonable hope that hewill be able to build muscle, to eat and breathe normally and hopefully also to walk even unassited first. With Sprinza this is less likely as Theo only has 2 copies of the backup gene on which the treatment works and so he does not have the same chance of achiveving a normal life with that therapy vs. Zolgensma.

Q3. What is Zolgensma and how does it compare to Spinraza ?

Zolgensma is a gene therapy that targets the cause of Spinal Muscular Atrophy. It replaces the missing SMN1 gene and gives the motor neurons the SMN protein that they need to survive. The treatment is given through an intravenous injection and is given only once in a lifetime. It works both in the central nervous system and peripheral organs (liver, heart, lungs etc.).

Spinraza was the first approved treatment for SMA and saved the lives of thousands of children all over the world, including Theo’s. As of today, it is the standard treatment in most European countries. It works through the backup gene, SMN2 to produce normal SMN protein. It is injected directly into the spine and works only in the central nervous system. It has to be given 4 times during the first 2 months (loading doses) and then once every 4 months (maintenance doses) for life. Although the drug itself is safe, the administration of lifelong lumbar punctures have significant risks to nerve damage, spinal headaches, radiation exposure etc. This is a very burdensome process for the child, the parents and also the medical system.

Zolgensma’s effect seems to go into every part of the body due to its systemic nature. So it works slightly better than Spinraza for motor skills and significantly better for respiratory and swallow functions. Based on the available data, it is incorrect to say that Zolgensma and Spinraza have the same effects for a SMA type 1 child.

The report published by the European Medicines Agency (EMA), which approved Zolgensma for use in Europe says: “Although another available treatment option is nusinersen (Spinraza), nusinersen treatment is associated with significant burden for the patient since it requires lifelong intrathecal injection (injection into spine), associated with safety risks. It is agreed that the data from Zolgensma assessed so far strongly suggests that the efficacy of Zolgensma in the intended patient population will exceed that of nusinersen (Spinraza). In addition, it is considered that given the difference in mechanism of action between nusinersen (Spinraza) and Zolgensma, Zolgensma is expected to be more efficacious in patients with 2 SMN2 copies since nusinersen (Spinraza) boosts the transcription of full-length protein from the SMN2 gene. Therefore, a major therapeutic advantage for Zolgensma is to be expected.” Page 147.


Children with SMA type 2 generally have better respiratory and swallow functions compared to SMA 1. It is unfair to compare the effect of Spinraza on children with SMA type 2 with the effect on children with SMA type 1, which is the most severe form of the disease. In the natural course of the disease in SMA type 1, swallowing begins to weaken usually around the first birthday. This was the case with Anika as well – an indication that Spinraza does not help Anika in that respect. If we want to stop the progression of Anika´s disease and restore the weakened functions, we must find access to a more efficient treatment. There are examples that show that Zolgensma can do that! Even though every form of SMA is scary, comparing a child with SMA 1 with a child with SMA 2 does not make sense, when it comes to the effectiveness of therapy or life-threatening effects of disease. While Zolgensma might be Anika´s only chance to stop life-threatening effects of SMA on her breathing and swallowing, Spinraza is still very good medicine that has saved many lives and brings increased life quality to many children and adults with different types of SMA.

Q4. Is Zolgensma a cure ?

Whether Zolgensma is a cure or not is difficult to answer. Children who receive Zolgensma before their symptoms appear develop like normal children. So, for these presymptomatic children, Zolgensma works like a cure. Children who are treated after their symptoms appear, sometimes achieve normal development, but it doesn’t apply for every child. In all cases, Zolgensma seems to produce positive results, but to different magnitudes. Therefore, we like to call Zolgensma an “almost cure”.

It is important to get Theo the Zolgensma treatment as soon as possible for two reasons. One reason is the crieteria means that he has to be under a certain weight limit and under the age of 2 years of age. The second reason, the lower his weight the less of the drug he needs to be given and thus safety is higher.

Q5. What are the long term effects of Zolgensma ?

A five year follow up study was published on May 17th 2021 this year Five-Year Extension Results of the Phase 1 START Trial of Onasemnogene Abeparvovec in Spinal Muscular Atrophy. The results are very promising, ‘These results support the favorable long-term safety profile of onasemnogene abeparvovec and provide evidence of sustained clinical durability of the therapeutic dose’. Children who received the approved dosage have continued to improve and show no sign of deterioration. Majority of them are not on any additional treatment. This would suggest also that the financially it is a better solution than Spinraza as the equivalent in Spinraza is 5 years * 300,000 euros + extra loading doses at beginning of treatment and children are expected to get stronger in time with the treatment which is required for life. Whereas with Zolgensma this is a once off procedure. The results suggest that the treatment will help Theo survive, and live a long and fulfilling life.

Q6. What are the options for our family to get Theo the treatment ?

We will know in next month or so if Theo is eligible for treatment for Zolgensma in France, where we will move to live for the year or more to ensure he is well looked after. Our second option is that the HSE review of the approval for Zolgensma. The stage of the process is managed by the Corporate Pharmaceutical Unit, HSE. Thee negotiations are still underway but hopefully there will be an outcome in November, I’ve contacted the HSE but have not received a reply yet.

If these two current options fail our next best bet is to start fundraising the money ourselves through crowdfunding. We have to do everything we can to give Theo the best chance at life possible and we are sure this is with Zolgensma. We will make our decision on fundraising likely end of November or as soon as we hear knews from the HSE.

There have been numerous good news stories in the last year or two at home and abroad of people being able to raise the funds in a short period of time. We heard about successful fundraising campaigns in Belgium, Netherlands, Hungary, Russia, Romania, Poland, Slovenia and Turkey. At home we heard of the do it for Dan campaign which unfortunately the funds were raised but he was not eligible, but they donated the funds to Team Livie who received the treatment in St. James in Dublin this year.

In the meantime our other action will be to invite everyone possible to sign a petition to make Zolgensma available for reimbursement in Ireland.

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