Research in the era of personalized medicine

Research in the era of personalized medicine

In early 2017, a neurologist at Boston Children’s Hospital named Timothy Yu began work on the most ambitious project of his life: devising and synthesizing an experimental drug for a dying child, within a few months.

Weeks earlier, Yu had been forwarded a desperate plea made on Facebook by a woman named Julia Vitarello. Her daughter Mila, then just five years old, had been diagnosed with Batten disease: a rare but devastating neurodegenerative disease that combines the symptoms of Parkinson’s disease, dementia and epilepsy. Worse, Mila’s form of Batten disease was driven by a unique genetic mutation, meaning no existing experimental therapy would work.

Rather than accepting her daughter’s fate, Vitarello became an activist, setting up a foundation in her daughter’s name. Through crowdfunding, she has raised more than $3 million ($2.4 million) to fund a new gene therapy. This eventually led her to Yu.

After sequencing Mila’s genome to identify the responsible mutation, Yu suggested developing a drug called “antisense oligonucleotide.” This relatively new treatment approach has recently been used to create a therapy for another rare disease called spinal muscular atrophy. Antisense oligonucleotides act by binding to the molecules produced by the mutated DNA, correcting their behaviour. But in this case it would be different. Yu allegedly created a custom antisense oligonucleotide designed exclusively for Mila.

At the time, it was the boldest drug development timeline ever attempted: synthesizing new drugs typically takes years instead of months. But in the winter of 2017, the drug, which was called “milasen”, was ready.

“I didn’t want my daughter to be the first to receive personalized medicine,” Vitarello says, 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 what is possible. We have the ability to find the underlying genetic cause of a disease and then pinpoint a drug to it, even if it’s unique to only one person.It was only after Mila started getting the drug that I started to really understand what a big deal it was.

Over the next four years, the treatment helped stop the progression of Mila’s condition and improved her quality of life. “Her legs got stronger so she could climb the stairs with my help,” says Vitarello. “She Laughed and smiled at funny things in books and songs. She Thought people sneezing was hilarious.”

Unfortunately, it came too late. The disease, already in an advanced stage, eventually returned. Mila passed away on February 11, 2021, aged just 10.

His mother still struggles with the loss. “What if he started taking the drug two months earlier, when he was still speechless and not having seizures. What if he’s been on it two years earlier or since birth? I have really difficult days. It comes unexpectedly, in waves.”

But two years later, Mila’s story began to spawn its own legacy. Unknown to her mother at the time, milasen’s development was followed by geneticists from around the world. They saw it as a seminal case for how genomics-based personalized 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 department of health, and a consultant at Great Ormond Street Hospital in London.

Mila’s story illustrates both the promise of personalized medicine, but also some of its frustrations. In theory, therapies targeting a person’s genetic makeup should be more effective and have fewer side effects. But in practice, personalized medicine is often irregular and expensive, and there are often simpler solutions. It also requires people to trust governments and companies with their genomic data, while the regulatory environment around drugs is ill-equipped to deal with therapies designed for just one person. Obtaining the safety and efficacy data needed for regulatory approval usually requires clinical trials involving hundreds, if not thousands of people.

However, researchers are still trying and now it looks like there could be some real progress.

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