Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses

Alfried Kohlschütter, Angela Schulz, Udo Bartsch, Stephan Storch, Alfried Kohlschütter, Angela Schulz, Udo Bartsch, Stephan Storch

Abstract

The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative lysosomal storage disorders caused by mutations in at least 13 different genes and primarily affect the brain and the retina of children or young adults. The disorders are characterized by progressive neurological deterioration with dementia, epilepsy, loss of vision, motor disturbances, and early death. While various therapeutic strategies are currently being explored as treatment options for these fatal disorders, there is presently only one clinically approved drug that has been shown to effectively attenuate the progression of a specific form of neuronal ceroid lipofuscinosis, CLN2 disease (cerliponase alfa, a lysosomal enzyme infused into the brain ventricles of patients with CLN2 disease). Therapeutic approaches for the treatment of other forms of neuronal ceroid lipofuscinosis include the administration of immunosuppressive agents to antagonize neuroinflammation associated with neurodegeneration, the use of various small molecules, stem cell therapy, and gene therapy. An important aspect of future work aimed at developing therapies for neuronal ceroid lipofuscinoses is the need for treatments that effectively attenuate neurodegeneration in both the brain and the retina.

Conflict of interest statement

Alfried Kohlschütter and Angela Schulz have been consultants to BioMarin Pharmaceutical Inc., Novato, CA, USA during a clinical trial of cerliponase A and have received fees, honoraria, and travel support. Stephan Storch and Udo Bartsch have no conflicts of interest that are directly relevant to the content of this review.

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