None approved; Milasen is a landmark personalized ASO (single-patient IND)
Batten disease is a group of inherited neurological disorders known formally as neuronal ceroid lipofuscinoses (NCLs). The CLN3 form (juvenile NCL) is the most common type, caused by mutations in the CLN3 gene. CLN3 encodes a lysosomal membrane protein involved in cellular waste recycling. When CLN3 is non-functional, lipofuscin-like ceroid material accumulates in neurons and other cells, causing progressive neurodegeneration.
Juvenile CLN3 disease typically begins between ages 5 and 10 with vision loss, followed by progressive cognitive decline, seizures, motor deterioration, and behavioral changes. The most common mutation is a 1 kb deletion that removes exons 7 and 8 of CLN3, accounting for approximately 85% of disease alleles.
Batten disease holds a unique place in the history of personalized antisense oligonucleotide therapy. In 2018, a team at Boston Children’s Hospital designed and administered a personalized ASO called Milasen for a single patient — Mila Makovec, a 6-year-old girl with a rare form of Batten disease (CLN7, caused by a MFSD8 mutation). Mila’s mutation was an intronic SVA retrotransposon insertion that created an aberrant splice site, leading to inclusion of a pseudoexon in the MFSD8 mRNA. The team designed an ASO to block this cryptic splice site, moved from target identification to intrathecal administration in less than a year, and received emergency IND authorization from the FDA.
Milasen demonstrated that the entire pathway from mutation identification to patient treatment could be compressed from years to months when an individualized approach is taken. It was a proof of concept not just for the ASO mechanism but for the personalized medicine model itself. The case was published in the New England Journal of Medicine and catalyzed regulatory and scientific discussions about personalized ASO treatments.
For CLN3 Batten disease specifically, the common 1 kb deletion removing exons 7 and 8 can potentially be addressed with exon-skipping or splice-switching strategies, depending on the specific mutation and reading frame context. Other CLN3 mutations, including point mutations and splice site variants, may require different ASO approaches.
Pequliar designs personalized ASO candidates for Batten disease, following the same design principles that enabled Milasen. The platform identifies the optimal ASO strategy based on the patient’s specific mutation, designs and scores antisense sequences, and provides synthesis-ready specifications. For families facing a Batten disease diagnosis, Pequliar automates the bioinformatics step of candidate identification — the same step that the Boston Children’s Hospital team performed manually for Mila.
Describe your mutation and get ranked, synthesis-ready ASO candidates in minutes. $399 per design.
Start a designPequliar is a computational research tool for informational purposes only. All sequences are computationally predicted candidates that have not been experimentally validated. Pequliar does not prescribe, recommend, or administer any compound. Independent validation by qualified professionals is required.