Lysosomal Acid Lipase Deficiency (LAL-D)
Lysosomal Acid Lipase Deficiency (LAL-D), including Wolman disease and cholesterol ester storage disease (CESD), stands as a rare autosomal recessive lysosomal storage disorder. In the realm of rare diseases, our company has emerged as a trailblazer, specializing in cutting-edge services that cater to the intricate needs of researchers and scientists.
Overview of LAL-D
The rare nature of LAL-D is underscored by its estimated prevalence range of 1:40,000 to 1:300,000 individuals. At the core of this disorder lies a deficiency in the enzyme lysosomal acid lipase (LAL), crucial for the breakdown of cholesterol esters and triglycerides within lysosomes. Consequently, the accumulation of these lipids in diverse tissues triggers a spectrum of debilitating symptoms affecting vital organs like the liver, spleen, and cardiovascular system.
Fig.1 The role of LAL-mediated lipid hydrolysis in cellular lipid homeostasis. (Korbelius, M., et al., 2023)
Pathogenesis of LAL-D
Driven by defects in the LIPA gene, LAL-D disrupts the intralysosomal degradation of cholesteryl esters and triglycerides, initiating a cascade of lipid buildup within tissues that culminates in inflammation, tissue damage, and organ malfunction. Among the most severely impacted organs are the liver and spleen, leading to complications such as hepatomegaly, splenomegaly, liver fibrosis, and potentially liver failure. Moreover, the deposition of lipids in blood vessels can precipitate cardiovascular issues like atherosclerosis, further complicating the landscape of LAL-D.
Fig.2 Structure of human LAL. (Korbelius, M., et al., 2023)Therapeutics Development of LAL-D
| Types | Drug Names | Mechanism of Action | Targets | Research Phase |
|---|---|---|---|---|
| Cell Therapy | Hematopoietic Stem Cell Transplantation | Rescue the deficiency of LAL | / | Clinical research |
| Enzyme Replacement Therapy | Sebelipase alfa | Recombinant human LAL | LIPA | Approved |
| Lipid-lowering Drugs | Lovastatin | HMG-CoA reductase inhibitors | HMG-CoA reductase | Approved |
| Ezetimibe | Inhibits the gastrointestinal absorption of cholesterol | NPC1L1 | Approved | |
| Gene Therapy | AAV-mediated gene therapy | Target LIPA expression | LIPA | Preclinical research |
Our Services
Our company has a team comprised of experts with in-depth knowledge and experience in rare diseases, with the advanced animal model and therapeutic development platform. By leveraging our expertise, resources, and commitment to advancing research in rare diseases like LAL-D, we aim to be the preferred partner for researchers and scientists seeking comprehensive support.
Therapeutics Development Platforms
Animal Models of LAL-D
Within the realm of translational research, animal models of LAL-D serve as invaluable tools for delving into the intricacies of the disorder, aiding researchers in elucidating disease mechanisms and evaluating potential therapeutic interventions. Our company spearheads the provision of diverse animal models tailored to facilitate groundbreaking research endeavors in this domain.
By feeding animals a high-fat diet rich in cholesterol and triglycerides, researchers can induce lipid accumulation in tissues and mimic aspects of LAL-D pathology.
Optional Models: High-fat diet model, etc.
These animal models are typically created by introducing mutations in the gene encoding LAL, leading to a deficiency of the enzyme and mimicking the human disorder.
Optional Models: Lipa-/- model, etc.
Why Choose Us
We offer a comprehensive suite of services including pharmacokinetic studies and drug safety evaluation, which are tailored to meet the diverse needs of researchers and scientists working in the field of rare diseases.
If you are interested in our services, we invite you to contact us for more information.
References
- Korbelius, Melanie et al. "Recent insights into lysosomal acid lipase deficiency." Trends in molecular medicine 29.6 (2023): 425-438.
- Pastores, Gregory M, and Derralynn A Hughes. "Lysosomal Acid Lipase Deficiency: Therapeutic Options." Drug design, development and therapy 14 (2020): 591-601.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.