Neuronal Ceroid Lipofuscinosis (NCL)
Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. Protheragen is committed to providing cutting-edge diagnostic and therapeutic development solutions to address the challenges of NCLs management. As your reliable partner in NCLs therapeutic research, we provide comprehensive and high-quality services to meet all your scientific research needs.
Introduction to Neuronal Ceroid Lipofuscinosis (NCL)
Neuronal ceroid lipofuscinoses (NCLs) represent a group of inherited lysosomal storage disorders characterized by progressive neurodegeneration, vision loss, and premature death. With an estimated incidence of 1 in 100,000 live births, NCLs are classified into more than 13 genetic subtypes (CLN1-CLN14), each defined by mutations in specific genes regulating lysosomal function.
Table 1 Some subtypes of neuronal ceroid lipofuscinoses (NCLs).
| Subtypes | Gene Defect | Onset Age | Hallmark Symptoms | Life Expectancy |
| CLN1 (Infantile) | PPT1 | 6–24 months | Rapid regression, blindness, seizures | <5 years |
| CLN2 (Late-Infantile) | TPP1 | 2–4 years | Myoclonus, ataxia, speech loss | 6–12 years |
| CLN3 (Juvenile) | CLN3 | 4–10 years | Visual failure, dementia, Parkinsonism | Teens to thirties |
| CLN6 (Variant Late-Infantile) | CLN6 | 3–8 years | Motor decline, seizures, cerebellar atrophy | 10–15 years |
Pathogenesis of Neuronal Ceroid Lipofuscinosis (NCL)
Neuronal ceroid lipofuscinoses (NCLs) are caused by genetic defects in lysosomal proteins (e.g., PPT1 in CLN1, TPP1 in CLN2) or membrane trafficking factors (e.g., CLN3, CLN6), leading to impaired autophagy and accumulation of toxic lipopigments (ceroid/lipofuscin) in neurons. This storage triggers mitochondrial dysfunction, oxidative stress, and neuroinflammation, resulting in selective neuronal death, particularly in cortical and retinal tissues. The specific mutated gene determines the subtype and severity of this progressive neurodegenerative cascade.
Fig.1 (A) CLN1 disease spreads in a "bottom-up" manner; (B) CLN3 disease spreads in a "top-down" manner. (Ostergaard J R, et al., 2022)
Therapeutic Development for Neuronal Ceroid Lipofuscinosis (NCL)
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| NGN-101 | AAV-mediated gene therapy delivering functional TPP1 enzyme | TPP1 gene | NCT05228145 | Phase I/II |
| AT-GTX-501 | Recombinant human PPT1 enzyme replacement with enhanced blood-brain barrier penetration | PPT1 protein | NCT02725580 | Phase I/II |
| CLN-301 | Monoclonal antibody targeting lipofuscin deposits to facilitate clearance | Pathological lipofuscin aggregates | NCT03770572 | Phase I/II |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
At Protheragen, we focus on preclinical research in neuronal ceroid lipofuscinoses (NCLs), providing comprehensive solutions from biomarker identification to development of CNS targeted therapeutics. Our expertise covers disease modeling, including patient-derived iPSCs, genetically engineered models, and advanced blood-brain barrier (BBB) models for evaluating drug penetration and neuroprotective efficacy. We provide partners with target validation, lead compound optimization, and comprehensive preclinical research services.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
- CLN1 Knockout Model
- CLN2 Knockout Model
- CLN3 Knockout Model
- CLN5 Knockout Model
- CLN6 Knockout Model
- Other Models
Protheragen takes pride in offering comprehensive preclinical research services for neuronal ceroid lipofuscinoses (NCLs) using advanced disease models. These services encompass various aspects of drug research, including pharmacodynamics (PD), pharmacokinetics (PK), and safety evaluations, ensuring a holistic approach towards drug development in this challenging medical area. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Ostergaard J R, Nelvagal H R, Cooper J D. Top-down and bottom-up propagation of disease in the neuronal ceroid lipofuscinoses[J]. Frontiers in Neurology, 2022, 13: 1061363.