Mila Makovec, a 6-year-old girl diagnosed with Batten disease, has showed stunning progress in a cutting-edge treatment involving personalized genomic medicine.
Batten disease falls within the family of Neuronal Ceroid Lipofuscinosis (NCL), a class of rare and fatal nervous system disorders. Batten is an autosomal recessive inherited genetic disorder, meaning that both parents must be carriers of the defective gene to pass it along.
Patients with Batten disease typically have problems with the function of lysosomes, organelles that help dispose of waste. By disrupting lysosomal function, the cells’ ability to dispose of waste and recycle molecules is compromised, causing certain proteins and lipids to build up. When too much waste builds up, the cells themselves begin to die.
The problem arises when neuronal cells — cells in the nervous system — are affected. Unlike other cells in the body, neuronal cells do not regenerate, which can result in rapid brain damage. Brain damage not only affects cognitive function but can also result in motor impairments and personality changes.
Batten disease affects approximately two to four births per 100,000 births in the United States. Symptoms of the juvenile Batten disease typically arise between five to 10 years of age, affecting vision first. Common symptoms following vision loss include seizures, dementia, abnormal movements, decline in cognitive abilities, and progressive loss of speech and other motor abilities.
Julia Vitarello and Alek Makovec, the parents of Mila Makovec, began to realize that something was wrong when their child began to lose her vision, her ability to speak and swallow, and her ability to walk. In December 2016, Mila was diagnosed with Batten disease.
Vitarello and Makovec were able to raise awareness of Mila’s condition by founding a non-profit called Mila’s Miracle Foundation. Through protein-sequencing, Mila’s doctors in Colorado were able to find the presence of a mutation of the CLN7 gene — a protein that most likely codes for lysosomal function.
During this long process, however, Dr. Cindy Lien, a physician at Beth Israel Deaconess Medical Center in Boston, caught word of Mila’s case. Lien took matters into her own hands and recruited Dr. Timothy Yu, a neurologist and neurogeneticist at Boston Children’s Hospital, who confirmed the CLN7 mutation and that Mila’s CLN7 gene was producing an ineffective protein.
Yu approved Mila for a clinical trial of a new gene therapy treatment using an antisense oligonucleotide which is able to “turn off” the defective gene.
In January 2018, with the approval of the U.S. Food and Drug Administration, Mila began her treatments. Mila’s parents posted updates on GoFundMe during this process.
“After a long, hard fight, we have finally arrived,” Vitarello wrote. “Just one year ago, Mila was given no hope. Now she has a real shot at life. But we face new questions around how Mila will respond. Will she improve? Will she flatline? Or will she get worse and have a bad reaction? The treatment is so new that there is no way to predict the outcome, and each possibility is real.”
Although there is no direct evidence of the CLN7 gene inhibiting the production of effective lysosomal proteins, the researchers were able to see a gradual decrease in the number and severity of Mila’s seizures with increasing treatment.
“We are in awe of our scientific team and what they have accomplished,” Vitarello wrote.
Mila’s personalized treatment seems to have not only halted the progression of Batten but also demonstrated the potential in using personalized medicine for other rare diseases.
Yu was excited about what Mila’s recovery could mean for medicine.
“I think this really does open up a path that could be applied to other genetic diseases,” Yu said, according to Science.
“We are in awe of our scientific team and what they have accomplished,” Vitarello said.
Mila’s personalized treatment seems to have not only halted the progression of Batten’s but has also demonstrated the potential in using personalized medicine for other rare diseases.
Yu was excited about what Mila’s recovery could mean for medicine. “I think this really does open up a path that could be applied to other genetic diseases,” Yu said in an interview with Science.