Cerliponase alfa for CLN2 disease, a promising therapy

ABSTRACT

Introduction: Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rare, lysosomal storage disease that causes progressive neurodegeneration in children. Cerliponase alfa enzyme replacement therapy is the first approved treatment for CLN2.

Areas covered: This article reviews the clinical presentation of CLN2, significant preclinical and clinical studies related to the approvals of cerliponase alfa enzyme replacement therapy (ERT) and other future disease modifying therapies like gene transfer. Authors also describe standard and novel surgical approaches and practical infusion considerations. Authors performed a comprehensive literature review using PubMed and ISI web of science. Inclusive dates of search were from September to October 2020.

Expert opinion: Prior to the approval of cerliponase alfa ERT, treatment was limited to symptomatic and palliative approaches. Cerliponase alfa intracerebroventricular therapy offers a safe and effective treatment option with long-term delay of disease progression. Current research indicates treated children have better outcomes in comparison to their natural history counterparts allowing preserved ambulation and language. Future research should be directed toward the discovery of therapies that may allow the delivery or promote production of functional CLN2 protein such as gene therapy.

KEYWORDS:

• CLN2 disease
• batten’s disease
• cerliponase alfa
• enzyme replacement therapy

Article highlights

• Cerliponase alfa intracerebroventricular therapy offers a safe and effective treatment option with long-term delay of disease progression with manageable adverse events.

• A multidisciplinary approach with key personnel including physicians, pharmacy, nurses and social workers are essential to the approach of the care of children with CLN2 disease.

• High cost and lifetime duration of this treatment modality may create financial and logistical barriers for families and institutions, and the impact of this long-term care needs further analysis.

• The emergence of disease modifying therapies have changed the landscape and outcome for children with rare disease. Gene transfer as a stand-alone therapy or to complement enzyme replacement therapy is a future avenue for research in CLN2 disease.

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Declaration of interest

E. de los Reyes has grant support and consultancy with BioMarin. S. Aylward has grant support with BioMarin. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.