A little girl destined to die, a disease diagnosed after two years, and a drug synthesized just for her. These are the ingredients of what appears to be the plot of a drama movie. What will the epilogue be?

It’s the story of Mila Makovec, a little girl who lives in Colorado and who, at the age of three, began to demonstrate very worrying symptoms: convulsions, reduced motor activity — to the point of being unable to lift her head — and the progressive loss of her vision. She had to wait two years and endure dozens of specialist medical examinations before arriving at the right place: Boston Children’s Hospital, in 2016.

Through innovative DNA sequencing techniques, with which I have been lucky enough to work more or less directly over the past ten years, it was possible for researchers to first diagnose the pathology, called Batten disease, and then identify the exact genetic defect linked to a gene called MFSD8 that encodes a protein, and that is fundamental for the action of lysosomes. Lysosomes are vesicles (i.e. a structure within or outside a cell) that are found in cells and destroy their waste.

Batten disease is an autosomal recessive disease, meaning that both parents must be carriers of the mutation. Its annual incidence is difficult to estimate, but there are data in Sweden that suggest that it is around 1 in 45,000, and in Germany 1 in 143,000. It usually occurs around the age of 6 and quickly leads to vision loss, cognitive decline and epilepsy. Dementia and motor disorders increase progressively, and unfortunately life expectancy is usually only about ten years after the onset of symptoms.

With this bleak picture, you can understand how apprehensive Mila’s parents were. Mila’s Mom in particular fought as only a Mom can, so she also founded a non-profit organization that raises funds to perform research on Batten disease.

What happened after the DNA sequencing?

The researchers did something unique and never attempted before: they developed an ad hoc drug, specific for Mila’s mutation; in fact, Batten disease is characterized by several mutations in different genes and this makes it, like many other diseases: difficult to diagnose and very difficult to treat.

Boston Children’s Hospital is a cutting-edge treatment and research institute, and the team that treated Mila has developed an oligonucleotide anti-sense drug. That is, they synthesized a small fragment of DNA, mirroring the sick one and therefore were able to mask the defect. Before using it on little Mila, the researchers performed tests on rodents, and the tests were so encouraging that the Food and Drug Administration (FDA) gave the go-ahead for the infusion of the drug. On January 31 2018, Mila was administered for the first time and the researchers named it “Milasen” in her honor.

Improvements were seen after only a short time, and now Mila is almost back to her normal life; she has largely recovered her motor skills, and in fact, she no longer needs the feeding tube in order to feed herself — she stands upright on her own, and her convulsions have decreased from 30 per day to a maximum of 6 per day.

It’s not yet known how long the treatment with this drug will extend her life, but it certainly (and unexpectedly) improved her quality of life.

It’s also a wonderful example of Personalized Medicine, where the combination of the skills of a state-of-the-art hospital, the determination of some individuals, and the generosity of many others, has pushed medicine another significant step forward. In this case, paraphrasing Neil Armstrong’s famous phrase, it can be said to be “a big step for a little girl” and “a huge step for all of humanity!”

This post is also available in: Italiano

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