Mila was three years old when her parents realized something was wrong. The little girl, who had previously been spinning, was climbing everywhere and jolly running around, suddenly curved her leg as she walked. Nor could she formulate complete sentences anymore. When Mila was four, she had difficulty seeing. In five years, she had become increasingly uncomfortable. "I was safe with 100 doctors near her, in the US and Canada," says mother Julia Vitarello on the phone. The family lives near Boulder, Colorado. "Nobody knew what she had."
When her condition suddenly worsened at the age of six, Mila came to the hospital. "She didn't react anymore and didn't even blink when her quick light shone in her eyes," the mother recalls. An MRI scan of the head showed that the tissue in Mila's brain had broken. A few more tests were followed by a devastating diagnosis: "Batten's disease." This is a very rare hereditary disease in which nerve cells in the brain die. "The doctors told us to enjoy the rest of our time with our child," Vitarello says, saying there is no help. Life expectancy of sick children is 8 to 12 years.
But Julia Vitarello sought help. Their Facebook call was accidentally read by neurogenetic wife Timothy Yu of Boston Children's Hospital. "Dr. Yu called us a few weeks later, "says Vitarello. He wanted to look for the cause of the disease. The parents' first hope, but it's no easy task for the researchers, because in Batten's disease, two copies of the gene from his father and mother were pathologically altered. mutation in Mila.
Only one year until therapy
Vitarello wanted to know the exact cause of the illness because Mila has a little brother. Can he get a serious illness too? "He was two and a half then," the mother says.
As neurogenetic agent Timothy Yu, along with a large research team, clarified the cause of Mila's disease and developed therapy specifically for her within just one year, scientists recently described the New England Journal of Medicine. The team thus laid the groundwork for personalized treatment of very rare genetic defects – first for those affecting the brain.
Yu and his team found a second genetic defect after analyzing the entire Milo genome. Although a DNA defect has never been described by Batten's disease before, it did remind the researcher of another genetic disorder: spinal muscular atrophy (SMA). The disease, which in its most severe form is fatal to 90 percent of diseased infants, has recently received innovative therapy in the United States. The active ingredient is called Nusinersen and has been approved as "Spinraza" in Switzerland since 2017.
"We have identified the path as personalized medicine also for other patients with very rare genetic defects. "Julia Vitarello, Mila's mother
Molecular biologists and geneticists have elegantly crafted the principle behind it. Short DNA-like molecules called antisense oligonucleotides (ASOs) are used. They intervene in the process of translating a gene into a protein. This process is similarly disrupted in SMA-affected individuals as in Mila, and the result is equally devastating for the sick: they cannot produce one important protein at a time. In patients with SMA, it is a protein called SMN, which is essential for muscle-stimulating nerve cells. Soap, however, lacks a sufficient amount of protein called CLN7. Required for waste disposal in cells.
So the research team could focus on the already approved Nusinersen active ingredient. "We used very similar chemical ingredients to make the Milo drug, like the drug maker in Nusinersen," says Charles Fiver of David Fischer. A US company conducted safety tests with ASO on animals.
Three million dollars costs
Mother Mila is immensely grateful to Timothy Yu's entire team. The researchers contacted the drug manufacturer after scientific testing, organized safety tests, and finally sought approval from the U.S. Food and Drug Administration (FDA). The cost of such experimental therapy paid as in Switzerland in the US, there is no health insurance. Vitarello founded the Mila's Miracle Foundation – and raised $ 3 million. Time was pressing. Just before Milain's seventh birthday, her condition worsened again. She could no longer pronounce words, barely swallowed, and had severe seizures, sometimes 15 to 30 daily for one to three minutes.
Meanwhile, laboratory experiments with Milas cells have shown that the prepared antisense oligonucleotides help to produce the CLN7 protein and that the cells are thus rendered almost healthy. Then rodent safety tests showed the substance was non-toxic. So the doctors got help from a drug agency, and Milain's family moved to Boston. In late January 2018, under general anesthesia, the girl received the first infusion of antisense oligonucleotides injected into the cerebrospinal fluid around the spinal cord, from where they entered the brain. Mila is a medicine called Milasen. "For the first four months, Mila received an infusion every two weeks," the mother says. "We were in the hospital for three days each."
In particular, the first half of the year was a success, says Vitarello. Mila could lift her head again, laugh, swallow, and she answered her colleagues. The number of seizures declined sharply.
"We saw very early on that Milasen had a positive effect," says David Fischer of Charles River. How great the effect is, Vitarello now says, "There are good weeks and bad ones." On the one hand, Mila is currently even better than other children with Batten disease. She can even do something with the help of her mother, which is no longer possible for other people at that age. On the other hand: Mila is not cured. Brain volume decreased even further. "The course of the disease is so rapid and the effects are often irreversible," Fischer says. Therefore, future patients should receive treatment as early as possible at the onset of Batten's disease, so hope.
Criticism of parents
"Some have criticized us for developing such experimental therapy for Milo," Vitarello says. Substances are poorly tried, which is unethical. "I find it unethical not to help my daughter." Vitarello also supports other people with its foundation. "We are paving the way for personalized medicine for other patients with very rare genetic defects," she says.
Mila has her birthday today. He is nine years old. "Yes, we will celebrate," says the happy mother. The brother will also be there. Genetic tests have shown that Julia Vitarello inherited one of the genes for Milo's disease – but not her son. He's healthy.
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Created: 04.11.2019, 17:43