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Tailor-made drug shows success in Batten disease

In an unprecedented move, a drug has been entirely custom-made for a young girl diagnosed with Batten disease; Mila Makovec.

The drug, dubbed “Milasen”, is a splice-modulating antisense oligonucleotide drug tailored to just the one person, which was found to cause no serious adverse events, and treatment was associated with objective reduction in seizures.

This study, funded by Mila’s Miracle Foundation and others, offers a possible template for the rapid development of patient-customised treatments.

Mila had developed the insidious onset of blindness, ataxia, seizures, and developmental regression. At five years old she came to medical attention because of modest language and social regression, as well as increased clumsiness and stumbling. In the months before she turned six, the progression of symptoms accelerated, and she was hospitalised after the rapid development of loss of vision, frequent falls, dysarthria, and dysphagia.

After obtaining written informed consent from Mila’s parents, the researchers obtained blood and skin samples for genomic and molecular characterisation under an appropriate human subjects research protocol.

Whole-genome sequencing was then undertaken to search for the missing second mutation, which was hypothesised to be a noncoding mutation or a structural variant missed by standard clinical sequencing.

At first Mila was having approximately 15 to 30 seizures per day, each lasting one to two minutes, but over the course of the clinical study, the frequency decreased to between zero and 20 seizures per day, and the duration of each seizure decreased to less than one minute.

The researchers also confirmed that Milasen remains an investigational drug, and it is not suited to the treatment of other patients with Batten’s disease because its design is customised to the specific patient’s specific mutation.

The success does, however, indicate that antisense oligonucleotides may deserve consideration as a platform for the rapid delivery of individualised treatments.