The Neuronal Ceroid Lipofuscinoses (NCLs) are inherited neurodegenerative diseases representing the leading cause of childhood dementia in Europe. NCLs are characterized by motor and cognitive decline, blindness, progressive myoclonic epilepsy, leading to fatal outcome within the third decade.
Autosomal inheritance is shared among all childhood forms. Twelve mutated genes have been identified so far, coding for proteins whose locations and functions are related to different cell compartments, including lysosomes. NCLs are worldwide distributed; in Italy, the prevalence is about 1/1000000, and 4-6 new patients a year are foreseen.
Advances in diagnostic tools, quality of assistance and therapeutic strategies led to improve the care of patients and their life expectancy. Recent improvement in the pathogenetic mechanisms of some forms paved the way for therapeutic possibilities (such as the approval of cerliponase alfa, an enzyme-replacement therapy for the CLN2 form) in what were previously considered fatal and untreatable conditions.
Aim of the Research Topic is to provide a multidisciplinary up-date of the state-of-art in NCLs. The following issues will be addressed by a number of experts in the field:
1. the clinical differences between the different forms (age of onset, main clinical features during the early stages, patterns of disease progression);
2. the genotype-phenotype relationship, and the phenotypic heterogeneity within each disease form; 3. the methodology to set up disease natural history, as a required tool by regulatory agencies to validate the efficacy of new therapies (either replacement therapies, or substrate reduction treatment, etc); 4. the pathogenetic mechanisms leading to nerve cell degenerations, focusing on the cell compartments targeted by the mutated gene products (such as lysosomes, ER, membranes, plasma membrane and ion channels, etc);
5. the epilepsy in NCL, focusing on the specific patterns (see CLN1 and CLN2 diseases), on the patho-mechanisms underlying seizure occurrence, on the principles of pharmacological treatment;
6. the steps of the care to be provided to the patients and the support for their families along the disease course; foundations of treatment shared with disorders leading to childhood neurodegeneration; 7. principles of ethics in care and treatment (including the state-of-art of targeted therapies).
The following issues will be addressed through a collection of dedicated, original articles:
1. NCLs as a disease group, keeping together different forms with selected clinical differences;
2. the phenotypic heterogeneity within each disease form, taking into account the genetic variants; 3. the methodology to set up disease natural history, and its relevance in clinical trials;
4. the pathogenetic mechanisms leading to nerve cell degeneration;
5. the interplay between lysosomes and other cell compartments;
6. the epilepsy in NCL, the specificity of EEG patterns, the treatment efficacy;
7. the care and the support to be provided to patients and their families;
8. ethics in care and treatment.
The Neuronal Ceroid Lipofuscinoses (NCLs) are inherited neurodegenerative diseases representing the leading cause of childhood dementia in Europe. NCLs are characterized by motor and cognitive decline, blindness, progressive myoclonic epilepsy, leading to fatal outcome within the third decade.
Autosomal inheritance is shared among all childhood forms. Twelve mutated genes have been identified so far, coding for proteins whose locations and functions are related to different cell compartments, including lysosomes. NCLs are worldwide distributed; in Italy, the prevalence is about 1/1000000, and 4-6 new patients a year are foreseen.
Advances in diagnostic tools, quality of assistance and therapeutic strategies led to improve the care of patients and their life expectancy. Recent improvement in the pathogenetic mechanisms of some forms paved the way for therapeutic possibilities (such as the approval of cerliponase alfa, an enzyme-replacement therapy for the CLN2 form) in what were previously considered fatal and untreatable conditions.
Aim of the Research Topic is to provide a multidisciplinary up-date of the state-of-art in NCLs. The following issues will be addressed by a number of experts in the field:
1. the clinical differences between the different forms (age of onset, main clinical features during the early stages, patterns of disease progression);
2. the genotype-phenotype relationship, and the phenotypic heterogeneity within each disease form; 3. the methodology to set up disease natural history, as a required tool by regulatory agencies to validate the efficacy of new therapies (either replacement therapies, or substrate reduction treatment, etc); 4. the pathogenetic mechanisms leading to nerve cell degenerations, focusing on the cell compartments targeted by the mutated gene products (such as lysosomes, ER, membranes, plasma membrane and ion channels, etc);
5. the epilepsy in NCL, focusing on the specific patterns (see CLN1 and CLN2 diseases), on the patho-mechanisms underlying seizure occurrence, on the principles of pharmacological treatment;
6. the steps of the care to be provided to the patients and the support for their families along the disease course; foundations of treatment shared with disorders leading to childhood neurodegeneration; 7. principles of ethics in care and treatment (including the state-of-art of targeted therapies).
The following issues will be addressed through a collection of dedicated, original articles:
1. NCLs as a disease group, keeping together different forms with selected clinical differences;
2. the phenotypic heterogeneity within each disease form, taking into account the genetic variants; 3. the methodology to set up disease natural history, and its relevance in clinical trials;
4. the pathogenetic mechanisms leading to nerve cell degeneration;
5. the interplay between lysosomes and other cell compartments;
6. the epilepsy in NCL, the specificity of EEG patterns, the treatment efficacy;
7. the care and the support to be provided to patients and their families;
8. ethics in care and treatment.