Milasen: The First Custom Drug

Meet Mila Makovec, an eight-year-old living in Colorado with her mother Julia. Mila had been like any other toddler until she lost her ability to see, eat, and even hold up her head on her own. Julia learned in December 2016 that her daughter had a disease called Batten disease, a rapidly progressing neurological disorder.

Mila began having symptoms of Batten disease when she was three years old. She suffered up to 30 seizures a day and required the use of a feeding tube to survive. Strangely, Mila only had one defective, disease-causing gene instead of the two usually needed for Batten to manifest. Dr. Timothy Yu and his colleagues at Boston Children’s Hospital found an explanation for this anomaly in March 2017. They discovered that, despite possessing a fully intact second gene, the gene had a small piece of extra DNA at the end that interfered with the production of an important protein, which led to the development of Batten disease.

Three years ago, the Food and Drug Administration (FDA) approved Spinraza, a drug that treats spinal muscular atrophy, another rare neurodegenerative disease. Spinraza works by blocking the effects of the gene mutation that causes spinal muscular atrophy. Dr. Yu believed that he could make a custom version of Spinraza for Mila by adapting Spinraza’s active ingredient to block the extra DNA Mila had. In just 10 months, Dr. Yu created and delivered “milasen,” named after the only person who would ever receive it.

Within just one month of treatment, Mila’s mother noticed that her daughter’s condition was less severe. Mila experienced fewer and shorter seizures with each passing day. After continued treatment, Mila experienced zero to six seizures a day, many of which did not last for long. Now, she rarely needs her feeding tube and can eat pureed foods. Though Mila is still unable to stand on her own, she can hold her neck and back straight when held upright. Though milasen will not cure her Batten, it will help stop the progression of the disease and prevent Mila’s untimely death.

Despite the happy ending to Mila’s story, the creation of the first “custom drug” raises many ethical questions. Many of these questions lie in the fairness of custom drugs. Pharmaceutical and insurance companies have little incentive to spend time and money researching and developing a drug that would be taken by only one person. The burden of paying for the creation and use of such a drug would therefore fall on the family of the patient. In Mila’s case, her mother managed to raise enough money to fund her daughter's treatment. However, not every family can do so. Only families who can gain the support of foundations or raise large sums of money would have custom drugs as an option for treatment. The possibility of custom drugs creates a greater disparity between the rich and the poor, where the rich would have access to these drugs while the poor would be shut out completely.

Currently, scientists do not have the technology to produce custom drugs quickly and cheaply. Developing all-new medicines, therefore, takes huge amounts of time: regular drugs take a decade to develop, with many of those years spent on clinical trials. For custom drugs, there is no need for repetitive safety trials, as only one person will receive them at a time. However, the efficacy of a custom drug cannot be measured for the same reason. A patient may wait for several years for their drug to be developed, only to find that it barely improves their quality of life.

The onset of custom drugs also brings up the uncomfortable notion of queues. It is difficult to determine who should have their potential cure developed first and therefore receive their drugs first. There are many factors in making this decision, such as the number of people with the disease or the severity of it, as well as the life expectancy of a person with a certain disease. A disease with many patients would appeal to researchers seeking a treatment plan, as a custom treatment for one person could be adapted for another person with the same or similar disease. In an ideal world, each person with a rare disease would receive the treatment they deserve. However, in the pharmaceutical world, one governed by money, this creates a dilemma in which certain groups of patients would be left without treatment options. The ultra-rich would be unaffected once again since they would be able to pay their way through treatment. “Abandoning” patients whose diseases are unprofitable could very well lead to social tensions resulting from the unfair distribution of healthcare.

However, there is still hope for personalized drugs. The advent of new medical innovations has given hope to those suffering from rare genetic diseases. Researchers have understood the functions of obscure sections of the human genome in genetic diseases, and this knowledge may one day lead to accessible treatments. The FDA has acknowledged the significance of personalized medicine by integrating it into their regulatory policies. The FDA has also outlined steps they would have to take to include genetic and biomarker information for clinical use and drug development.

Mila’s story has become one of hope for those suffering from rare diseases. Despite the ethical questions surrounding custom drugs, proof of concept has been shown, which is all that is needed to give hope to millions of families around the world.