The neuronal ceroid lipofuscinoses (NCLs) comprise a group of incurable neurodegenerative storage disorders primarily affecting the brain and the retina of children and young adults, leading to dementia, blindness, epilepsy, and early death. |
For one specific form of NCL (CLN2 disease), replacement of the dysfunctional lysosomal enzyme through intraventricular infusion of a functional enzyme (cerliponase alfa) has recently been shown to effectively attenuate the progression of the disease in patients. |
Other potential treatment options for NCLs include small molecule therapy, neuroprotection, stem cell therapy, and gene therapy, in addition to enzyme replacement therapy. |
As vision loss is among the characteristic clinical symptoms of most NCL variants, treatments are needed that attenuate retinal degeneration in addition to neurodegeneration in the brain. |
1 Introduction
Designation of disease | OMIM | Gene | Protein | Cellular localization | ||||
---|---|---|---|---|---|---|---|---|
CLN1 disease | Infantile | Late infantile | Juvenile | Adult | 256730 | CLN1 (PPT1) | Palmitoyl protein thioesterase 1 (PPT1) | Soluble lysosomal protein |
CLN2 disease | Late infantile | Juvenile | 204500 | CLN2 (TPP1) | Tripeptidyl peptidase (TPP1) | Soluble lysosomal protein | ||
CLN3 disease | Juvenile | 204200 |
CLN3
| CLN3 | Lysosomal membrane protein | |||
CLN4 diseasea | Adult | 162350 | CLN4 (DNAJC5) | Cysteine string protein α (CSP α) | Cytosolic, associated with vesicular membranes | |||
CLN5 disease | Late infantile | Juvenile | Adult | 256731 |
CLN5
| CLN5 | Soluble lysosomal protein | |
CLN6 disease | Late infantile | Adult | 601780 |
CLN6
| CLN6 | ER membrane protein | ||
CLN7 disease | Late infantile | Juvenile | 610951 | CLN7 (MFSD8) | CLN7 | Lysosomal membrane protein | ||
CLN8 disease | Late infantile | Juvenile | 600143 |
CLN8
| CLN8 | ER membrane protein | ||
CLN10 disease | Congenital | Juvenile | Adult | 610127 | CLN10 (CTSD) | Cathepsin D (CTSD) | Soluble lysosomal protein | |
CLN11 disease | Adult | 614706 | CLN11 (GRN) | Progranulin | Soluble lysosomal protein | |||
CLN12 disease | Juvenile | 610513 | CLN12 (ATP13A2) | ATP 13A2 | Lysosomal membrane protein | |||
CLN13 disease | Adult | 615362 | CLN13 (CTSF) | Cathepsin F | Soluble lysosomal protein | |||
CLN14 disease | Infantile | Late infantile | 611725 | CLN14 (KCTD7) | Potassium channel tetramerization domain-containing protein type 7 | Cytosolic, partially associated with membranes |