MNDRIA's Beryl Bayley Postdoctoral Fellow, Dr Michelle Farrar from the University of NSW, is spearheading Australian research into an emerging treatment called nusinersen that has been shown in clinical trials to improve motor development in babies and children with spinal muscular atrophy (SMA), a disease of the motor neurones that most often affects infants. Several Australian infants have participated in these pivotal clinical trials.
While nusinersen is approved by the US Food and Drug Administration, it has not yet been approved by the Therapeutic Goods Administration. Michelle's research has enabled a baby girl to be given the drug for free as part of an Expanded Access Program. She is the ninth infant with SMA type 1 in the world to access nusinersen outside a clinical trial. Results to date have been positive with ongoing research required to provide more information about the long-term benefits of the drug.
Before the discovery of nusinersen, there was no treatment for SMA. Results from Michelle's MNDRIA-funded research project – Motor neurone diseases in children and young people – understanding pathophysiology and developing treatment approaches – provide hope to children and families affected by the disease. Animal models of MND suggest that treatment approaches like nusinersen may be suitable for other types of MND.
The following FAQs were prepared by MNDRIA's Beryl Bayley Postdoctoral Fellow, Dr Michelle Farrar:
What is spinal muscular atrophy?
Spinal muscular atrophy (SMA) is a genetic disease that most often affects children. Like adult motor neurone disease (MND), SMA affects the motor neurones of the spinal cord, causing muscle weakness and wasting.
The most severe types of SMA result in the death of children before two years of age. Although a rare disease, SMA is the number one genetic cause of death in infants, affecting 1 in 6000 children.
SMA is caused by abnormalities in the SMN1 (Survival Motor Neuron 1) gene. When the SMN1 gene does not function properly the SMN protein cannot be produced, which causes motor neurones in the spinal cord and brainstem to die. This process may start before birth, so some children may show symptoms in the first few weeks or months of life.
There are three types of SMA that affect children: SMA type 1, SMA type 2 and SMA type 3. Like adult MND, SMA is a very complex disease that affects each person differently.
What does this new research mean?
In the past, the treatment of SMA has focused on managing complications caused by weakness, feeding and breathing difficulties. There has been no specific treatment for SMA. This has changed with the discovery of a drug called nusinersen (or Spinraza), which has been shown in clinical trials to improve motor development in babies and children with SMA types 1 and 2. Nusinersen works by helping a backup gene to produce a protein that makes up for the faulty SMN1 gene that causes SMA.
Results of some clinical trials are pending, but the information available to date suggests that this drug is more effective when administered early in the disease course. Ongoing clinical trials will provide more information about the long-term benefits of this drug. In Australia, several infants have been enrolled in nusinersen trials and there is a lot of activity in setting up more clinical trials.
How might this research influence MND research?
Nusinersen has been tested in children with SMA who have mutations in the SMN1 gene. The strategy of targeting the core genetics of SMA may be translatable to genetic types of MND in the future, e.g. MND caused by inheritance of mutations in the SOD1 gene.
Currently, nusinersen must be injected into the spinal fluid of infants affected by MND several times a year. A team of Australian researchers is developing new forms of therapies that are easier and less invasive to administer that may be suitable for people with SMA and other types of MND.
Animal studies have also suggested that increasing the SMN protein may have some benefit in sporadic MND. Read more
Is this a new treatment for MND?
An Extended Access Program (EAP) for SMA type 1 is happening in Australia so that infants with SMA will be able to access Nusinersen – free of charge to the patient, hospital or state – before it goes through the full process of regulatory approval in Australia. That regulatory process could take months or years.
I have more questions, who should I ask?
For further information talk to your neurologist or contact your local State MND Association.