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Collaboratives, Companies Mobilize to BuildMomentum for 'N-of-1' ASO Therapies

Jessica Kim Cohen (Precision Medicine Online)

October 30, 2023


NEW YORK – A neurologist at Boston Children's Hospital in 2018 created what was widely reported as the first medicine developed for a single patient: a 7-year-old girl, Mila, who suffered from a fatal neurological condition. But it will be years before that therapeutic approach becomes accessible for many other rare genetic diseases.


Kateryna Kon/Science Photo Library/Getty Images

The personalized medication, named milasen after the young patient, was created and administered just one year after Mila was diagnosed with Batten disease, a congenital condition in which patients progressively lose neurological function and experience frequent seizures. Scientists led by Timothy Yu, the neurologist who treated Mila, used antisense oligonucleotides (ASOs) to target Mila's specific genetic mutation.


Mila's story, which reached the international news circuit after investigators published a report of the drug development and treatment process in the New England Journal of Medicine, put a spotlight on ASOs as a potentially scalable approach to treat various rare genetic diseases. Since then, a spate of consortiums, non-profits, and research efforts have cropped up to build on this momentum and attempt to create paths forward for getting treatments from the lab to the clinic. These efforts, though, face regulatory, ethical, funding, and other barriers.


More than a dozen ASO therapies have been approved by the US Food and Drug Administration for

multiple diseases since the first therapy, Ionis Pharmaceuticals' Vitravene (fomivirsen), was greenlit by the regulator as a treatment for cytomegalovirus retinitis in 1998 — though none for indications as rare as Mila's N-of-1 mutation. Most recently, the FDA granted accelerated approval to Biogen's Qalsody (tofersen) as a treatment for a genetic form of amyotrophic lateral sclerosis (ALS), which is estimated to affect about 3,000 patients globally.


But Yu and colleagues at his lab at Boston Children's designed milasen to target the specific mutation that Mila harbored in one copy of the MFSD8 gene that caused her form of Batten disease. As an ASO therapy, milasen comprised short strands of modified DNA designed to target messenger RNA of a defective gene — in this case, MFSD8 — and correct the abnormality.


While milasen improved Mila's quality of life by suppressing her seizures, the disease had already

progressed to an advance stage by the time it was administered, and Mila died from Batten disease at the age of 10 years old in 2021. Still, Mila's mother Julia Vitarello, who continues to advocate for

improvements to rare disease treatment, said her story has represented hope for the field.


Kim Cohen, J. (n.d.). Collaboratives, companies mobilize to build momentum for “n-of-1” aso ... Precision Medicine Online. https://www.precisionmedicineonline.com/inherited-disease/collaboratives-companies-mobilize-build-momentum-n-1-aso-therapies

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