Introduction to treatments
Spinal Muscular Atrophy (SMA) is a rare, genetic neuromuscular condition causing progressive muscle wasting (atrophy) and weakness leading to loss of movement. This may affect walking and upper body movement, breathing and swallowing. Importantly, SMA does not affect a person’s ability to think, learn or build loving relationships with others.
Does my child have SMA?
Early diagnosis means early intervention. Learn more about the symptoms of SMA here: www.signsofsma.com
Should you have any concerns, contact your child's healthcare provider without delay. Email firstname.lastname@example.org for support and more information.
What causes SMA?
Patients with the disease lack a protein called 'survival motor neuron' (SMN), which is essential for the normal functioning and survival of motor neurons. Without this protein, the motor neurons deteriorate and eventually die. This causes the muscles to fall into disuse, leading to muscle wasting (atrophy) and weakness.
The SMN protein is made by two genes, the SMN1 and SMN2 genes. Most patients with spinal muscular atrophy lack the SMN1 gene but have the SMN2 gene, which mostly produces a 'short' SMN protein which cannot work properly on its own.
There are different forms of SMA and a wide spectrum of how severely children and adults are affected. The most common form is known as ‘5q SMA’; referring to the chromosome containing the genetic cause.
When a child or adult is first diagnosed, the doctor gives a clinical classification - SMA Type I, II, III or IV - which reflects the age of onset of symptoms and the motor milestones that someone would be expected to achieve. The severity of the condition varies from person to person, both within and between ‘Types’ - each is affected differently.
Spinraza was developed by Biogen and was approved in Ireland for treating patients with SMA Types I, II or III in June 2019. It works by increasing production of the survival motor neuron (SMN) protein, which is essential for the function and survival of motor neurons.
Most SMN protein is produced by the survival motor neuron 1 (SMN1) gene. Individuals with SMA lack sufficient functional SMN1 due to mutations in this gene. The related survival motor neuron 2 (SMN2) gene can also produce SMN protein, but only about 10% of the amount from SMN1. The more copies of SMN2 an individual has, the milder their SMA tends to be.
Spinraza is an antisense oligonucleotide drug that binds to RNA produced by the SMN2 gene. It works as a 'molecular patch' to prompt increased production of full-length SMN protein containing all essential components.
Treatment involves loading doses given directly into the spinal canal, followed by maintenance doses given every 4 months. Spinraza increases SMN protein levels in motor neurons, which may help preserve muscle function.
In Ireland, Spinraza is currently reimbursed by the HSE for patients under 18 years old with SMA Types I, II or III. An application was submitted in 2020 to extend reimbursement to adults as well. The outcome is still pending but would provide an important new treatment option for adults with SMA in Ireland.
Zolgensma (onasemnogene abeparvovec) is a gene therapy that was approved for reimbursement in Ireland by the HSE in November 2021. It is designed to address the underlying genetic cause of spinal muscular atrophy (SMA).
In SMA, a defect in the survival motor neuron 1 (SMN1) gene results in insufficient production of the SMN protein, which is essential for motor neuron function. Zolgensma provides a functional copy of the SMN1 gene via an adeno-associated virus vector. This allows motor neurons to produce enough SMN protein to improve nerve and muscle function.
Zolgensma was developed by Avexis, now part of Novartis Gene Therapies, and received EMA approval in May 2020. It is administered as a one-time intravenous infusion. Due to the high cost, strict criteria determine which patients qualify for Zolgensma in Ireland:
- Confirmed genetic diagnosis of 5q SMA
- Clinical diagnosis of SMA Type I, or presymptomatic with bi-allelic SMN1 mutations and ≤3 copies of SMN2
- Age under 24 months at time of treatment
- Weight restrictions may also apply
By providing a functional SMN1 gene, Zolgensma aims to halt progression of SMA if given early enough, transforming the lives of affected children.
Evrysdi (risdiplam) is an 'anti-sense oligonucleotide' medicine similar to Spinraza. It works by modifying splicing of messenger RNA from the survival motor neuron 2 (SMN2) gene, leading to increased production of functional SMN protein.
Unlike Spinraza which is injected into the spinal canal, Evrysdi is administered orally in a liquid solution taken daily at home. This offers greater convenience for patients.
Evrysdi was approved by the European Medicines Agency in August 2021 and in August 2023, the HSE approved reimbursement in Ireland as a monotreatment for patients aged no more than 18 years old with a clinical diagnosis of SMA type I, II or III, with 1-4 SMN2 copies. For comprehensive details, see HSE Risdiplam Criteria
The number of adults in Ireland without access to any treatment totals approximately 16. SMA Ireland deeply regrets that these adultsmost of the click are currently excluded from this treatment, despite substantial evidence of its efficacy in patients up to 60 years of age.
This arbitrary age limit of 18 is not only distressing but also lacks scientific justification. SMA Ireland remains committed to advocating for the inclusion of adults in the treatment criteria and will continue its campaign to address this critical issue.