Mesenchymal Stem Cell-Based Therapy for Lysosomal Storage Diseases and Other Neurodegenerative Disorders

Abstract

Lysosomal storage diseases (LSDs) are a group of approximately 50 genetic disorders caused by mutations in genes coding enzymes that are involved in cell degradation and transferring lipids and other macromolecules. Accumulation of lipids and other macromolecules in lysosomes leads to the destruction of affected cells. Although the clinical manifestations of different LSDs vary greatly, more than half of LSDs have symptoms of central nervous system neurodegeneration, and within each disorder there is a considerable variation, ranging from severe, infantile-onset forms to attenuated adult-onset disease, sometimes with distinct clinical features. To date, treatment options for this group of diseases remain limited, which highlights the need for further development of innovative therapeutic approaches, that can not only improve the patients’ quality of life, but also provide full recovery for them. In many LSDs stem cell-based therapy showed promising results in preclinical researches. This review discusses using mesenchymal stem cells for different LSDs therapy and other neurodegenerative diseases and their possible limitations.

Left-sided valvular heart disease and retinopathy in a 38-year-old woman with attenuated mucopolysaccharidosis: a case report

“…Stem cell–based approaches have shown promise in preclinical trials. 18 – 20 Multipotent adult mesenchymal stem cells (MSCs) derived from bone marrow are of particular interest. MSCs have self-renewing and multi-lineage differentiation capacity.…”

“…MSCs are easily accessible and cultured in the clinical setting from the bone marrow of the specific patient (autologous) or from donors (allogeneic). 18 In addition, MSCs are known to be immune-privileged and can be genetically modified with lentiviral or adeno-associated viral transduction to overexpress specific defective lysosomal enzymes. 18 Another novel therapeutic approach employed for MPS I is the autologous transplantation of both hematopoietic stem cells and progenitor cells that have been transduced ex vivo with an IDUA-encoding lentiviral vector after myeloablative conditioning.…”

“… 18 In addition, MSCs are known to be immune-privileged and can be genetically modified with lentiviral or adeno-associated viral transduction to overexpress specific defective lysosomal enzymes. 18 Another novel therapeutic approach employed for MPS I is the autologous transplantation of both hematopoietic stem cells and progenitor cells that have been transduced ex vivo with an IDUA-encoding lentiviral vector after myeloablative conditioning. 20 Preliminary data from these studies show promising results including a similar safety profile to autologous hematopoietic stem cell transplantation, prompt and sustained engraftment of gene-corrected cells and supraphysiologic blood IDUA activity within a month, and decreased urinary GAG excretion.…”

Gene and Cell Therapy for Epilepsy: A Mini Review

“…It is important to select a suitable donor in the case of allogeneic transplantation, not only in terms of HLA compatibility, but also in the heterogeneity of effector molecules secreted by the cells, which vary considerably between different donors and can lead to a significant variation in the treatment efficacy ( Montzka et al, 2009 ; Mukhamedshina et al, 2019 ). The migration ability of cells also imposes restrictions on the use of cell-based therapy in clinical practice since highly invasive cell delivery is sometimes required to reach the target area and cross the blood-brain barrier ( Issa et al, 2020 ).…”

Gene Therapy of Sphingolipid Metabolic Disorders

“…ERT is considered the current standard of care for sphingolipidoses, and most currently approved drugs are based on this type of treatment. However, most sphingolipidoses affect the central (CNS) and peripheral nervous systems, which is a limiting factor for the use of ERT [ 59 , 60 ]. Gene therapy seems to be a promising approach for sphingolipidose treatment.…”