Neuronal Ceroid Lipofuscinosis (NCL)
Neuronal ceroid lipofuscinosis (NCL) refers to a group of conditions that affect the nervous system. With our pioneering efforts in NCL research, we are at the forefront of developing cutting-edge diagnostic tools and therapeutics to facilitate the effective management of NCL. As your reliable partner in NCL research, we offer unmatched support to fulfill your scientific research needs.
Overview of NCL
Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is a group of rare and devastating neurodegenerative disorders primarily affecting the nervous system, particularly in childhood. These inherited conditions lead to the accumulation of lipofuscins, within cells, impairing their normal function and ultimately resulting in cell death. NCL is relatively rare, with an incidence of approximately 1 in 25,000.
Fig. 1 Dysregulation of the endocytic and autophagic pathways in LSDs including the NCLs. (Mukherjee, et al., 2019)NCL encompasses various subtypes, each characterized by distinct genetic mutations and differing presentations. The genetic mutations associated with NCL affect the normal functioning of lysosomes, cellular organelles responsible for degrading and recycling unwanted materials. As a result, waste products such as lipofuscin accumulate, leading to cellular dysfunction and subsequent neuronal death.
Table. 1 Relationship between major subtypes of NCL and mutated genes
| NCL Subtypes | Description | Gene |
|---|---|---|
| CLN1 | Ceroid lipofuscinosis, neuronal, 1 (CLN1), also known as infantile NCL, begins between approximately 6 months and 2 years of age and progresses rapidly. | PPT1 |
| CLN2 | Ceroid lipofuscinosis, neuronal, 2 (CLN2), also known as late infantile NCL, begins between 2 and 4 years of age. | TPP1 |
| CLN3 | Ceroid lipofuscinosis, neuronal, 3 (CLN3), also known as juvenile NCL, begins between the ages of 5 and 8 years. | CLN3 |
| CLN4 | Ceroid lipofuscinosis, neuronal, 4 (CLN4), also known as adult NCL, generally begins before age 40 and causes milder symptoms that progress slowly. | CLN6, DNAJC5 |
Diagnostics Development of NCL
Diagnostic methods for NCL encompass a comprehensive approach, including genetic testing, enzyme activity assays, electroencephalography (EEG), neuroimaging, and histopathological examination.
- Genetic testing plays a pivotal role in identifying specific mutations associated with NCL subtypes, enabling precise diagnosis and genetic counseling.
- Enzyme activity assays provide valuable insights into the deficiency of lysosomal enzymes, further aiding in subtype classification.
- EEG and neuroimaging techniques help detect characteristic abnormalities in brain activity and structure, respectively.
- Histopathological examination of tissue samples confirms the presence of lipofuscin accumulation, validating the diagnosis.
Therapeutics Development of NCL
Enzyme Replacement Therapy (ERT)
In the case of NCL, ERT aims to supplement the deficient lysosomal enzymes responsible for the degradation of lipofuscins. Brineura™ (cerliponase alfa) is an FDA-approved enzyme replacement therapy for the therapy of CLN2. It has demonstrated efficacy in slowing the rate of decline in motor and language function in affected children.
Gene Therapy
Gene therapy holds immense promise for the therapy of genetic disorders like NCL. In NCL, where specific genetic mutations disrupt lysosomal function, gene therapy aims to deliver the corrected gene to affected cells, enabling the production of functional lysosomal enzymes. Several preclinical studies are underway to evaluate the safety and efficacy of gene therapy approaches for NCL.
Small Molecule Therapies
Small molecule therapies are currently being explored to restore cellular homeostasis, reduce lipochrome accumulation, and mitigate neurodegeneration in NCL. Research in this area involves the identification and development of small molecules that can penetrate the blood-brain barrier and exert therapeutic effects within the central nervous system.
Our Services
With years of extensive involvement in rare disease research, our company boasts a highly skilled team and vast expertise. We harness state-of-the-art technology to drive the development of innovative diagnostic tools, enabling early detection of NCL. By establishing animal models and conducting in-depth investigations into NCL pathogenesis and targets, we advance therapeutic drug development.
Our Research Platforms
Our Services
Animal Models of NCL
| Genetically Engineered Models | ||
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| At our company, we specialize in developing genetically engineered models for NCL research. Our expertise in genetic engineering techniques, such as CRISPR/Cas9 technology, allows us to generate accurate and reliable models that recapitulate the genetic alterations observed in NCL individuals. | ||
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| Optional Species | Mice, Zebrafish, Fruit Flies, Dogs, Sheep, Cattle, Others | |
No matter what stage of research you are at, we can provide you with corresponding research services. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Mukherjee, Anil B., et al. "Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses." Molecular neurodegeneration 14 (2019): 1-23.
- Specchio, Nicola, et al. "Neuronal ceroid lipofuscinosis: potential for targeted therapy." Drugs 81 (2021): 101-123.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.