Personalized Medicine: A Drug Tailored for a Six Year Old With Batten Disease May Serve as a Template for Similar Rare Disorders


Mila Makovec began her life as a normal, healthy infant, and according to a recent article in Science Magazine, she continued along this path until reaching the age of six.

Her parents did notice some early warning signs but it was not until 2016, when Mila was about to turn six, that her symptoms had progressed so rapidly that she was hospitalized.

Tests showed that her brain volume was shrinking. That was the obvious cause of her seizures, partial loss of vision, balance, and slurred speech.

Genetic testing led to the devastating diagnosis of Batten disease. It is a rare genetic disorder of the nervous system and it causes death in late childhood or by mid-teens.

About Batten Disease

Batten disease has thirteen forms, CLN1 through CLN13, but all forms seem to be associated with cells called lysosomes.

In 2016 Mila’s doctors identified a mutation in the CLN7 gene that proved to be Batten disease.

Lysosomes are called the “recycle bin” of the cell. They breakdown proteins, waste and lipids that are then discarded or recycled.

The CLN7 mutation disturbs the cells by limiting their ability to dispose of waste. The cells are thrown off balance due to the resulting build-up of proteins and lipids (fats).

Mila’s doctors made a thorough examination of her genome and discovered that an extra piece of DNA had found its way into the CLN7 gene.

This prevented the cell from reading the gene’s instructions because the instructions were being cut off.  As a result, the cell was unable to make the full protein.

Doctors at Boston Children’s Hospital Offered Help

 Neurologist Timothy Yu heard of Mila’s condition and together with his co-workers had a strand of RNA synthesized with the intention of masking the CLN7 gene that was causing the death of Mila’s brain cells.

The first step was to prove that an antisense oligonucleotide drug that they named “milasen” was able to correct the defective CLN7 found in cells that were cultured from Mila’s skin. Milasen is similar to a recently approved drug (brand name Spinraza) for spinal muscular atrophy.

Doctor Yu explained that antisense oligonucleotides are synthetic molecules composed of genetic material (nucleic acids) that are capable of concealing the error in order for the full protein to be produced.

Within one year, by January 2018, the doctors were given FDA approval to begin treatment. They started infusing RNA into Mila’s spinal fluid. Results from the first year of her treatment suggest an improvement in the number and duration of her seizures.

Interim Results

 Prior to the study, Mila had about fifteen to thirty seizures daily. Each seizure lasted about two minutes. During the treatment, the frequency fell to between zero and twenty seizures daily with the duration of the seizures lasting about one minute.

A measurement of Mila’s brain waves confirmed a decline of about fifty percent in the number of seizures and their duration. Although to date there have been no harmful side effects, it is uncertain what effects the drug may have on Mila in the future.

Dr. Yu reported his interim results in the October 9, 2019 edition of the New England Journal of Medicine. His team reported that Mila is still losing brain volume but her seizures remain suppressed and other neurological tests have shown improvement or have stabilized.

It should be noted, however, that Mila’s symptoms progressed rapidly while she waited for her treatment to begin. By the time the doctors were able to begin treatment, Mila’s condition had deteriorated to a point where she was unable to see, walk or speak without assistance.

A Template For the Future

Dr. Yu described Mila’s treatment in terms of how it can impact patients in the future. He suggested using the procedure as a template for the rapid development of personalized genetic treatments.

Dr. Yu noted, however, that this drug cannot be used to treat other patients because it was specifically tailored for Mila’s mutation. He explained that the drug, in its current form, may be used only for extremely severe life-threatening disorders.

The FDA cautioned that this type of therapy must be carefully evaluated as desperate parents may believe that they are witnessing improvement without clinical evidence.

Regulators must first decide on the amount of lab data that should be submitted before the drug is administered to patients.

Dr. Yu has recently been advising doctors who are treating a woman with an oligonucleotide matching a mutation that causes amyotrophic lateral sclerosis. Yet he explains that his team is not prepared to have further discussions with other families that have contacted his Boston lab.

Mila’s Miracle Foundation Website

Mila’s family started Mila’s Miracle Foundation Website to find a cure for Batten disease and similar neurological diseases. Information about donations to the charity may be accessed here.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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