David Cox (BBC)
June 4, 2023
The Human Genome Project was supposed to lead to personalised medicine tailored to our DNA. It's finally happening, but it is proving more difficult than anyone could have imagined.
In early 2017, a neurologist at Boston Children's Hospital called Timothy Yu began work on the most ambitious project of his life: to design and synthesise an experimental drug for a dying child, within a timeframe of just a few months.
Weeks earlier, Yu had been forwarded a desperate plea made on Facebook from a woman called Julia Vitarello. Her daughter Mila, then just five years old, had been diagnosed with Batten disease: a rare but devastating neurodegenerative disorder combining symptoms of Parkinson's disease, dementia, and epilepsy. Worse, Mila's form of Batten disease was driven by a unique gene mutation, meaning no existing experimental therapies would work.
Rather than accept her daughter's fate, Vitarello became an activist, setting up a foundation in her daughter's name. Through crowdfunding, she raised more than $3m(£2.4m) with the aim of funding a novel gene therapy. This ultimately led her to Yu.
After sequencing Mila's genome to identify the responsible mutation, Yu suggested developing a drug called an "antisense oligonucleotide". This relatively new treatment approach had recently been used to create a therapy for another rare disease called spinal muscular atrophy. Antisense oligonucleotides work by binding to the molecules produced by the mutated DNA, correcting their behaviour. But in this case, it would be different. Yu would create a personalised antisense oligonucleotide designed solely for Mila.
At the time it was the most audacious drug development timeline ever attempted: synthesising new medications typically takes years rather than months. But by the winter of 2017 the drug, named "milasen", was ready.
"I didn't set out for my daughter to be the first to receive a personalised medicine," says Vitarello, speaking to the BBC from her home in Colorado, US. "I was hoping we could find the mutation that was causing her disease, but then milasen, the drug Tim Yu developed for Mila, showed just what is possible. We have the ability to find the underlying genetic cause of a disease and then target a drug to it, even if it is unique to just one person. It was only after Mila started receiving the drug that I started to really understand what a big deal that was."
Over the next four years, the treatment helped to halt the progression of Mila's condition, and improved her quality of life. "Her legs got stronger so she could go up stairs with my help," says Vitarello. "She laughed and smiled at funny things in books and songs. She though people sneezing was hilarious."
Unfortunately, it came too late. The disease, already in an advanced stage, eventually returned. Mila died on 11 February 2021, aged just 10.
Her mother still wrestles with the loss. "What if she had started receiving the drug two months before when she still had her words and wasn't suffering seizures. What if she had got it two years earlier or from birth? I have days that are really hard. It just comes unexpectedly, in waves."
But two years on, Mila's story has begun to generate it's own legacy. Unknown to her mother at the time, the development of milasen was followed by geneticists around the world. They saw it as a landmark case of how genomic-driven personalised medicine could be used to tackle rare diseases. "This story is a really powerful example of what's possible," says Richard Scott, chief medical officer at Genomics England, which is run by the UK's department of health, and a consultant at Great Ormond Street Hospital in London.
Mila's story illustrates both the promise of personalised medicine, but also some of its frustrations. In theory, therapies targeted to a person's genetic makeup should be more effective and have fewer side effects. But in practice, personalised medicine is often erratic and expensive, and often there are simpler solutions. It also requires people to trust governments and companies with their genomic data, while the regulatory environment around medicines is ill-equipped to cope with therapies that are designed for just one person. Getting the safety and efficacy data needed for regulatory approval usually requires clinical trials involving hundreds, if not thousands of people.
Nevertheless, researchers are still trying – and it now seems there may be some genuine progress.
Cox, D. (2023, June 15). The quest for the era of personalised medicine. BBC Future. https://www.bbc.com/future/article/20230602-are-we-entering-the-era-of-personalised-medicine