Referral Notes:

  • CLN2 Batten disease is a rare pediatric neurodegenerative disorder that leads to seizures, motor decline, dementia, and blindness.
  • Cerliponase alfa, an enzyme replacement therapy, is approved for intracerebroventricular use; off-label intravitreal delivery may prevent vision loss.
  • In late 2024, NYU Langone specialists were the first in the country to administer intravitreal cerliponase alfa outside of a research setting, with the patient maintaining a stable eye exam.
  • NYU Langone is uniquely positioned to offer access to emerging Batten-specific therapies in the New York metropolitan area.

Specialists at NYU Langone Health are helping to pioneer a new treatment strategy for neuronal ceroid lipofuscinosis type 2 (CLN2) Batten disease.

The rare pediatric lysosomal storage disorder is often characterized by early onset, progressive neurodegeneration. In its classic form, affected children experience normal development until ages 2 to 4 before developing language delay and seizures, followed by rapid loss of motor, cognitive, and visual function.

Cerliponase alfa is an enzyme replacement therapy for CLN2 disease that slows the loss of motor and language function. However, because the agent cannot cross the blood–retina barrier when administered as an infusion into the fluid-filled spaces of the brain, the ventricles, it does not slow the progression of retinal degeneration. As a result, patients may still develop blindness despite their motor and cognitive symptoms being managed.

NYU Langone ophthalmologist Zachary Elkin, MD, MPH, and neurogenetics specialist Nicolas J. Abreu, MD, associate director of the Division of Neurogenetics, developed a protocol for intravitreal delivery of cerliponase alfa. In late 2024, NYU Langone became the first center in the country to administer cerliponase alfa to a patient as an intravitreal injection outside of a research setting.

“Our first patient has had a stable eye exam for over a year, and she has passed the age when vision may begin to deteriorate.”

Zachary Elkin, MD, MPH

“A small study from the UK was the first to suggest that intravitreal delivery of cerliponase alfa could preserve retinal function and morphology in patients with CLN2 disease,” explains Dr. Elkin. “This data, combined with personal communications with collaborators conducting a clinical trial of intravitreal cerliponase alfa at Nationwide Children’s Hospital in Ohio, served as the basis for writing our protocol.”

“Our first patient has had a stable eye exam for over a year,” adds Dr. Elkin, “and she has passed the age when vision may begin to deteriorate.”

Designing and Implementing the Protocol

CLN2-associated retinal degeneration is characterized by early degeneration of the macula, followed by a primary degeneration of the outer retinal layers and a secondary degeneration of the inner retinal layers.

As the disease progresses, retinal degeneration leads to complete loss of the outer retinal layers in the fovea and later in the perifovea—and ultimately affects the entire macula and peripheral retina—resulting in blindness. “Our goal is to prevent blindness in these children,” says Dr. Elkin.

To develop the protocol, the researchers convened experts from neurogenetics, ophthalmology, pharmacy, nursing, and anesthesia to design and implement a process for off-label delivery of cerliponase alfa directly into the vitreous cavity of the eye.

Their goal was to make the treatment process as seamless as possible, ensuring that those treated with standard intracerebroventricular infusions could safely receive the intravitreal injections concurrently.

“We are committed to ending the ocular complications of this disease.”

Nicolas J. Abreu, MD

First, patients who are deemed appropriate for intravitreal injections are brought to the operating room for a diagnostic examination under anesthesia. During this exam, fluorescein angiography, optical coherence tomography, and RetCam® images are collected. After receiving the intravitreal injection, the patient is transferred for their intracerebroventricular infusion.

One patient at NYU Langone has been treated to date. Although there is no specific age restriction, the goal is to initiate therapy prior to the onset of retinal degeneration. Individuals who have already experienced complete vision loss are not considered candidates for this treatment.

Excellence in Batten Disease

As one of seven nationally recognized Batten Disease Centers of Excellence from the Batten Disease Support, Research, and Advocacy Foundation, NYU Langone is uniquely positioned to provide Batten-specific care, pioneer research, and offer access to emerging therapies, particularly in the New York metropolitan area. Dr. Abreu also serves as site principal investigator and co-leads the Career Development Core for the NIH-funded Batten Disease Clinical Research Consortium.

Since developing the intravitreal protocol, Drs. Elkin and Abreu have begun helping other institutions across the country implement it. They hope it will become the standard model for treating children with CLN2 Batten disease.

“These patients should not be predestined for blindness,” Dr. Abreu says. “We are committed to ending the ocular complications of this disease.”

Disclosures

Dr. Abreu has received funding from BioMarin Pharmaceutical, the manufacturer of cerliponase alfa.