Background of Hematopoietic Stem Cell Transplantation for Lysosomal Storage Diseases
Lysosomal storage disorders (LSDs) are a large group encompassing more than 40 different genetic disorders caused by defects in the activity of one or more lysosomal hydrolases. LSDs are often classified according to the nature of the primary storage material. Broad categories include mucopolysaccharide storage disorders (MPS), sphingolipid storage disorders, mucolipid storage disorders, glycoprotein storage disorders, oligosaccharide storage disorders, and glycogen storage disorders. Hematopoietic stem cell transplantation (HSCT) has been identified as an effective treatment for selected inborn errors of metabolism. The basic principle of HSCT is that the donor cells can migrate into the recipient's organ and correct the metabolic defect by locally releasing the missing enzyme. Due to the slow and incomplete process of HSCT, success in treating severe neurological disorders is limited. Nevertheless, HSCT remains the treatment of choice for certain lysosomal diseases, including the severe form of MPS I (Hurler disease).
Fig. 1. Process by which HSCT treats patients with MPS. (Taylor M, et al., 2019)
Solutions
HSCT relies on the use of hematopoietic stem cells derived from a healthy donor as a therapeutic agent. Our team of experts has extensive theoretical knowledge and experience in HSCT technology. With years of experience in drug development strategies for lysosomal storage diseases, CD BioSciences offers customized HSCT solutions for LSDs. Our cutting-edge HSCT platform allows for a dual effect.
❖ Replacement and repopulation of specific tissues with healthy cells from the donor.
❖ Associated with the secretion of functional lysosomal hydrolases by donor cells in the extracellular space and into the circulation. The secreted normal enzymes may be taken up by recipient cells and may cross-correct enzyme defects in these cells.
CD BioSciences offers hematopoietic stem cell transplantation drug discovery strategies for LSDs including, but not limited to:
Transplantation of Wild-Type Autologous Cells
We establish MPS animal models, and use autologous hematopoietic stem cells to isolate progenitor cells from the mice themselves that can be transduced in vitro with wild-type copies of the defective gene, transforming the hematopoietic system into a "factory" for enzyme production and/or secretion.
Transplantation of Genetically Engineered Autologous Cells
We provide autologous hematopoietic stem cells and gene therapy vectors designed to increase enzyme production in transplanted cells and their progeny. Our genetically engineered autologous cell transplantation can do the following:
(ⅰ) Increase the benefit potential of HCT by increasing the dose of enzymes delivered to affected tissues by the progeny of transplanted cells. We achieve this by developing efficient gene transfer vectors that allow individual cells to produce higher than normal amounts of enzyme.
(ⅱ) Significantly reduced morbidity and mortality associated with transplantation due to the use of milder pretreatment regimens and the absence of graft-versus-host disease (GvHD) in the autologous environment.
Advantages of HSCT Solutions for LSDs
- HSCT produces functional enzymes in donor-derived cells capable of migrating to the brain, thereby delaying neurocognitive degeneration.
- HSCT is indicated as an attenuated form of treatment for MPS I, Klabber's disease, and heterozygous cerebral white matter dystrophy.
- Comprehensive development of genetically modified autologous cells to enhance enzyme delivery.
- Customized HSCT solutions.
CD BioSciences' mission is to provide preclinical HSCT therapeutic strategies for lysosomal storage diseases that provide new ideas for drug discovery. We look forward to collaborating with you in the discovery of innovative LSD therapeutic strategies. If you are interested in our solutions, please feel free to contact us.
Reference
- Taylor M, et al. (2019) Hematopoietic stem cell transplantation for mucopolysaccharidoses: past, present, and future[J]. Biology of Blood and Marrow Transplantation. 25(7): e226-e246.