Dubai researchers have developed a new test for spinal muscular atrophy that can better identify those whose genes put them at risk of developing the debilitating condition.
Created by scientists at Al Jalila Children’s Specialty Hospital, the new technology means 13 per cent of patients whose illness would be missed with standard testing will now receive a diagnosis.
Another advantage of the new approach, says Dr Ahmad Abou Tayoun, director of the hospital’s genomics centre, is that it picks up a wide range of genetic variants associated with SMA in a single test.
"Otherwise, patients currently go through a cascade of sequential testing using different technologies, each optimised to detect a single variant type, to get a diagnosis," Dr Abou Tayoun said.
Such a barrage of tests is likely to be "at a much higher cost" and risks delays in diagnosis and treatment, potentially missing the time window for proper management of the condition.
Dr Abou Tayoun and his co-researchers have released their findings as a pre-print scientific paper before it has been reviewed by other scientists.
Their new testing approach is not yet in wide use but is expected to become "more and more routine" as it is perfected over time.
"The test can be used for newborns or older children and adults," Dr Abou Tayoun said. "This technology can be extremely fast, as data can be analysed while being generated."
What is spinal muscular atrophy?
SMA affects motor neurons, which are nerve cells that send impulses to the muscles and causes weakness in the limbs.
Some people with the condition cannot or find it difficult to walk, while SMA may also make swallowing and breathing difficult.
Children who have the most severe form, type 1, and who are not treated, are unable to sit unsupported and typically die before their second birthday, according to the US National Institutes of Health. Symptoms of type 1 begin to manifest within the first six months of life.
Type 2 causes less severe symptoms but may prevent a child from walking.
Two other forms, type 3 and type 4, affect older children and adults, with milder but still significant symptoms.
SMA’s genetic basis is better understood than that of some other neurological conditions, such as Alzheimer’s or Parkinson’s disease.
A mutation in a gene called SMN1, which codes for a protein called SMN or survival of motor neuron, causes types 1 to 4.
People have a copy of the SMN1 gene from each parent and if only one of these has the mutation, that individual does not develop SMA.
One in 40 to 60 people is a carrier, meaning they have a copy of the mutation but do not develop symptoms.
There is a one-in-four chance that any child of two carriers will inherit two defective forms of SMN1 and therefore have SMA. Between one in 6,000 and one in 10,000 newborns will develop the condition.
New treatments described as "game-changing" have been released in recent years but for their benefit to be maximised, children should be started on them as early as possible.
Costly treatment
Among the new therapies is Zolgensma, which is a form of gene therapy because it provides a working SMN gene to cells, enabling them to produce the SMN protein.
It is administered only once but has been described as the world’s most expensive drug as the single treatment costs a reported $2 million (Dh7.35 million).
Also available are gene-based treatments that have to be administered on a number of occasions at a cost of several hundred thousand dollars a year per patient.
A key characteristic of the new test developed in Dubai is its ability to identify "methylation signatures" associated with SMA.
Methylation is the process in which methyl groups, which are chemical units with similarities to methane, become attached to the DNA that makes up genes.
It is a type of epigenetic factor, meaning that it influences gene expression – the process by which genes produce proteins – without any changes to the sequence of the DNA in and around the genes.
Dr Abou Tayoun said "we currently have no idea" what causes the methylation, and trying to understand this "will now be a whole new area of research".
"If, perhaps, we revert them, that could potentially be a way to treat this disease, given the current expensive gene therapy treatment for around $2 million," he said.
"All we know is that this signature is specific to the SMN1 gene, whose deletion is causing the disease. Further work will be carried out to understand how and why."
Previous research has shown that treating cells with a demethylating agent can increase expression of genes that produce the SMN protein.
As reported in The National, Dr Abou Tayoun and his co-researchers have also recently developed a simpler and cheaper SMA screening test for newborns.
