Enzyme Treatment Slows Decline Caused by CLN2 Batten Disease
Study published in the New England Journal of Medicine indicates early treatment may prevent damage.
With every diagnosis of CLN2 Batten disease, Emily de Los Reyes, MD, had a difficult conversation with parents.
“I told parents this is a brain disorder that will result in the early death of your child and that you may see your child melt before your eyes,” says Dr. de Los Reyes, a neurologist and director of the Nationwide Children’s Batten Disease Center of Excellence. “Now, I can tell them that we have a treatment. Or maybe even a cure if children get the treatment before they lose function.”
Dr. de Los Reyes and Lenora Lehwald, MD, an attending neurologist at Nationwide Children’s and co-investigator of the CLN2 trials, led the U.S. portion of an international study that shows an enzyme treatment delivered directly to the brains of children with CLN2 significantly slows motor and language declines. The response rate was 87 percent at 96 weeks.
The study is published in the New England Journal of Medicine.
CLN2 is caused by the lack of the enzyme tripeptidyl peptidase 1 (TPP1). Without a functioning TPP1 enzyme, lysosomal storage material accumulates and causes degeneration throughout the central nervous system.
Most children with the disease function normally until ages 2 to 4. Then, they typically begin showing language delay followed by seizures. A rapid decline in motor, language, cognitive and visual function follows. Most die by early adolescence.
– Emily de Los Reyes, MD
In this study, 23 children, ages 3 to 16, received an infusion of cerliponase alfa, a recombinant proenzyme form of human TPP1, every two weeks for at least 96 weeks.
During the 96 weeks, none of the treated children suffered an unreversed 2-point decline on a CLN2 clinical rating scale of their language and motor skills. Medical records of comparable untreated children, historical controls, show they reached a mean 2-point decline in skills at just under a year.
The decline rate per 48-week period was a mean of 0.27 points among treated children versus 2.12 points among historical controls.
Differences in motor, language, cognitive and visual function measurements between the treated and untreated children grew over time, indicating the treatment benefit persisted.
The youngest two participants began the study with no signs of impairment due to CLN2 and continue to have none. That suggests early treatment may provide the greatest benefit, Dr. de Los Reyes says.
To test that theory, the researchers are now studying the treatment in children younger than 3 years.
Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P, Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A, CLN2 Study Group. Study of intraventricular cerliponase alfa for CLN2 disease. New England Journal of Medicine. 2018 May 17;378(20):1898-1907.