Custom-made oligonucleotide therapy for girl with fatal Batten disease

By Sarah MooreReviewed by Kate Anderton, B.Sc. (Editor)Oct 14 2019

Sufferers of fatal Batten disease have been given new hope as scientists develop a custom-made therapy for a young girl. The drug has been shown to reduce the symptoms of the condition and slow the rate of cell death that is characteristic of the disease.

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A potential new treatment for a disease that is always fatal

Doctors at Boston Children's Hospital met Mila Makovec in 2017. Mila had been diagnosed with incredibly rare Batten disease which is untreatable and fatal.

For those suffering from the disease, the condition gets progressively worse, and affected children face a loss of eyesight, cognitive impairment, seizures, and loss of motor skills. As the condition worsens with time the person becomes bedridden, and dies prematurely, as early as in their childhood years.

For Mila, she was already facing faded vision at the age of four, had trouble walking at the age of five, and by six she had become completely blind and could hardly speak.

The cause of these irreversible and highly impactful symptoms on the affected person’s quality of life is due to a variety of genetic mutations. These mutations prevent the cells usual function of breaking down and getting rid of waste, leading to a buildup of waste in the brain cells, causing the premature death of the cells.

Hope has been given to those affected by the disease as results from a new study have demonstrated how doctors at Boston Children's Hospital were able to develop a tailor-made drug for Mila, which was able to successfully amend certain errors of her DNA.

While the drug has not cured her of Batten disease, the frequency of her seizures has significantly reduced since the drug trial began, and doctors have also seen her cognitive function stabilize. This indicates that the custom-made drug is likely to be slowing down the speed at which the disease is progressing.

How the customized drug was created

Published in The New England Journal of Medicine, the team at Boston explain that they performed whole-genome sequencing on Mila’s DNA in order to identify where the unique mutation was located that was responsible for causing the disease. In successfully identifying the genetic fault the doctors saw an opportunity to target it to treat Mila.

They began work creating a drug that could target the genetic error. They first tested it on Mila’s cells in the lab as well as on animals. Following the success, the US Food and Drug Administration approved it for single use. While drug development often takes years of progress, usually around 15 years, Mila’s custom-made drug was approved on 31 January 2018, a year after doctors first met with Mila.

Could the therapy be used to help others with Batten disease?

While the drug was specifically designed to treat Mila, it has given others hope of a possible treatment to slow this fatal disease, and even cure it. The doctors at Boston hope that they can further develop this kind of treatment, and believe that intervening at an even earlier stage may be the key to an even more significant slowing of the disease, this is because they cannot undo the damage - only prevent it.

In addition to acting as a treatment model for other individuals with Batten disease, doctors believe that Mila’s case could also inform future treatments for other inherited central nervous system diseases.

However, much work needs to be done before this kind of treatment could be made available to the masses, if it ever could. Doctors highlight that there are significant potential side effects along with the necessity to deliver the drug into the spinal fluid, and therefore it should only be considered in cases of life-threatening diseases.

Please note, the research team is not yet ready to discuss treatment with other patients.