Lysosomal storage diseases (LSDs) are a group of metabolic disorders caused by deficiencies in several components of lysosomal function. This group includes about 70 monogenic disorders of lysosomal catabolism characterized by a progressive accumulation of nondegradable substrates in the lysosome, which in turn leads to cellular dysfunction, tissue damage, and death. Most commonly affected are lysosomal hydrolases, which are involved in the catabolism and recycling of a wide range of complex molecules and cellular structures. Most diagnoses of LSD are made after an accurate clinical/paraclinical assessment, including analysis of a number of urinary metabolites, based primarily on the detection of specific enzyme deficiencies. The development of new technologies based on high-throughput methods is now making a significant contribution to the characterization of lysosomal biology or lysosomal dysfunction and has the potential to facilitate the diagnostic process and enable the identification of new therapeutic targets.
Fig. 1. Current lysosomal storage disorder therapeutic strategies. (La Cognata V, et al., 2020)
Lysosomal Function Analysis Services in Lysosomal Storage Disease
CD BioSciences is committed to providing our global clients with a comprehensive service to analyze lysosomal changes and dysfunction in lysosomal storage diseases, primarily by detecting lysosomal hydrolase activity in a number of biological fluids (e.g. plasma, serum and urine). The selection of the type of sample to be analyzed is based on,
(i) the level of enzyme activity in a given tissue.
(ii) stability of the sample during transfer to the referring laboratory.
(iii) time to assay.
Due to the lack of specific lysosomal enzymes in LSDs, a common biochemical hallmark of these diseases is the accumulation of undigested metabolites in the lysosomes. Our scientists characterized the biochemistry of LSDs by identifying the primary storage material of LSDs and identifying the respective enzyme defects. In addition, we establish a generative technology platform for targeted gene disruption and knockout animal models of human LSD to better characterize the pathophysiology of LSD. Based on our advanced high-throughput technologies with novel techniques for bioinformatics analysis, we offer the following services.
- Identification and characterization of novel genes associated with lysosomal diseases.
- Search for LSD biomarkers.
- Characterization of lysosomal biology in LSD.
- Identification and validation of novel therapeutic targets associated with lysosomes in LSD.
In collaboration with international cytologists, we use CRISPR-Cas9 and iPSC approaches to develop cellular models of LSD, allowing the identification of novel pathways involved in the physiology and pathogenesis of LSD, and for drug screening to identify new drugs for the treatment of these diseases. We also offer animal (small multi-species such as mice and rats) models of LSD through targeted knockout and knock-in technologies that allow the study of drug pharmacokinetics, bioavailability, toxicity and the assessment of metabolic responses and functional measurements in organs and tissues.
Our Available Technologies
- Metabolomics.
- Genomic technologies and next generation sequencing (NGS).
- Proteomics approaches.
- Automated robot-based technologies.
- Cell-based assays and high-content imaging technologies.
Advantages of Our Services
- Multiple cutting-edge technologies.
- Allows manipulation of genetic information and generation of in vitro and in vivo LSD models.
- Identifies abnormal accumulation of biomarkers or metabolites that can be used as LSDs.
- Comprehensive, more fine-grained analysis services.
- Explore new identified therapeutic targets for lysosomal-related diseases.
Our professional services for the analysis of lysosomal changes and dysfunction in lysosomal storage disease have been well received by customers. Our highly skilled and dedicated scientific staff ensures that the most appropriate method and technology is selected for each specialized lysosomal project. If you have any special requirements about our services, please feel free to contact us. We are looking forward to working together with your attractive projects.
Reference
- La Cognata V, et al. (2020) Highlights on Genomics Applications for Lysosomal Storage Diseases[J]. Cells. 9(8): 1902.