Children with late-infantile onset Batten disease (CLN2) may be treated with an enzyme replacement therapy (ERT). However, this therapy cannot reverse the damage or progression children have already experienced. Researchers are exploring alternate options to provide more targeted care to children with CLN2. According to Marisa Wexler, MS, in Batten Disease News, one promising option – an experimental gene therapy called AAVrh.10hCLN2 – recently performed well in a study examining the therapy in non-human primates.

AAVrh.10hCLN2 delivers a functional copy of CLN2 to nerve cells. Children with late-infantile onset Batten disease have CLN2 mutations. This presents them from creating tripeptidyl peptidase 1 (TPP-1), a protein that breaks down waste products within cells. As a result, these waste products build up to toxic levels. By delivering a working copy of CLN2, AAVrh.10hCLN2 would allow the body to clear out those wastes from cells.

Within the study, published in Human Gene Therapy, researchers evaluated AAVrh.10hCLN2 in African green monkeys. In particular, the research team wanted to understand whether intracisternal magna administration (through the cerebrospinal fluid) was more effective than intraparenchymal administration (through the skull to a certain area in the brain). A prior study explored intraparenchymal administration in children with CLN2. They found that, while safe and enduring, intraparenchymal administration failed to stop CLN2 from progressing – even though it slowed that progression.

The research team discovered that TPP-1 levels in the cerebrospinal fluid rose in monkeys treated with AAVrh.10hCLN2. Further, TPP-1 brain expression was higher than seen through intraparenchymal administration. AAVrh.10hCLN2 was also safe. As a result, researchers believe that future studies should focus more on intracisternal magna administration to identify if this route could benefit those with CLN2.

About Late-Infantile Onset Batten Disease

Also known as: CLN2; CLN2 disease; Jansky-Bielschowsky Disease

There are multiple forms of Batten disease, with the four main forms considered infantile, late-infantile, juvenile, and adult. This rare inherited nervous system disorder is often fatal by late teens and early 20s. In late-infantile Batten disease, symptoms often appear between two and four years old, with a normal lifespan of eight to twelve years. MedLine Plus explains that symptoms of late-infantile Batten disease may include:

• Recurrent seizures
• Vision loss
• Developmental regression
• Progressive intellectual disability
• Muscle twitching
• Ataxia (impaired movement and coordination)
• Behavioral difficulties
• Language delays
• Frequent falling