n of 1

Newborn screening programmes offer the chance to detect genetic diseases earlier and treat them. But there are some huge dilemmas about the technology

Photo by Jewel Afflerbaugh.

Julia Vitarello is sitting in a child's bedroom. Behind her, the bed is neatly made with a white coverlet and soft toys. What is missing, so painfully, is her daughter Mila. She died over a year ago at the age of 10 of a very rare and fatal genetic disorder known as Batten disease. The error created a deficiency in a metabolic enzyme which, in turn, meant that proteins and lipids built up in her brain causing neurodegeneration.

Children like Mila, with inborn errors of metabolism, spend years developing normally. They learn to run or cycle and have friends. Then, tragically, they regress and die. When she was seven, Mila became the first person in the world to receive a tailor-made medicine. The drug, a molecule known as an "antisense oligonucleotide" was designed to bind to, and silence, her faulty genetic code—something that allowed the correct enzymes to be produced.

The drug, called milasen, arrived in time to suppress her seizures and improve her quality of life, but far too late to save her. From a now-empty bedroom, Julia says she feels an enormous sense of responsibility to other children because "Mila showed what was possible". But to turn that possibility into reality, we need to find these children earlier in life. And that poses a difficult conundrum.

To understand the problem, let us take a look at the bigger picture. More than 7,000 rare diseases are known and three-quarters are genetic in origin. Most are exceptionally serious if not fatal. And although any single genetic disorder is rare, collectively they are a huge problem. Global Genes, an American advocacy group, says that 400m people around the world are affected by them, half of which are children. This is the “long tail” of medicine that has been hard for pharma companies to work on. Not only are there small numbers of patients but diseases are discovered too late. 

Scientists and pharma firms are also working on treatments one gene at a time. It is painfully slow progress. Tragically so, if you happen to be the parent of a child who is ill. Mila's story showed that finding the underlying genetic cause of her disease--in her case a single genetic mutation--opened up a pathway to treatment. And because there are often only one, or a handful, of patients with a mutation like Mila's treating such diseases is often referred to as "n of 1"-- a reference to the fact that the number (or n) of patients testing a medicine is small and individualised. 

If progress can be made on developing n-of-1 therapies more quickly, and cheaply, so they can be adapted to a variety of different mutations, this will offer a route to curing rare diseases all around the world. But to start developing drugs for these ultra-rare genetic conditions, one needs to diagnose them earlier. And the way to do that is through newborn genetic screening.

As it happens there are plans to expand newborn genetic screening all around the world. I recently published a piece in the Science section, for which this post is overmatter. Alongside was a leader (op-ed) at the front of the magazine. And today our podcast The Intelligence published a further conversation on the subject (free to listen).

One of the contentious issues is over the extent of genetic tests. Some parents do not want to know about diseases that there may be no cure for. And some doctors don’t want to test for diseases that involve invasive follow-ups such as liver biopsies or lumbar punctures. That is because if one needs to screen lots of healthy babies with these follow-up tests, you may end up doing more harm to children. What this means is that public health bodies are likely to test for a more limited set of diseases as standard practice—that is certainly what is emerging from a public consultation underway in Britain.

Although not all parents want to know about all their child’s genetic diseases at birth (and thus run the risk that they will have to live with years of anxiety over the child’s future), some, like Julia, do and will. These parents consider that “knowledge is power”. The benefit of finding out more at birth is that there might be the option to join a trial, or find an individualised therapy. It is these parents that will fuel the next step in progress on the long tail of medicines. For scientists working on custom-anti-sense oligonucleotides, they need to do more to identify children with genetic diseases—whether currently treatable or not—earlier in life.

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Notes:

Julia Vitarello is the founder and CEO of Mila’s Miracle Foundation, and Genomics England is currently consulting on the future of a public newborn genetic screening programme. This piece was overmatter from the Science & Technology section of The Economist.