[LS4-1D-1] Novel Therapeutic Approaches of Neurological Involvement of Lysosomal Storage Disease
Lysosomal storage diseases are monogenic disorders du to congenital deficiency of lysosomal enzymes resulting in progressive accumulation of several molecules.
Mucopolysaccharidoses (MPS) are congenital deficiency of lysosomal enzymes responsible for degradation of glycosaminoglycans (GAG). In MPSI and MPSII, dermatan sulfate(DS) and heparan sulfate(HS) accumulate in lysosome. In MPSVI, MPSIII, and MPSIV, DS, HS, and keratin sulfate(KS) accumulate, respectively. Mental retardation and regression are observed in MPSI, II, and III, suggesting accumulated HS in CNS is neurotoxic. Enzyme replacement therapy (ERT) is available in MPSI, II, IVA, and VI, but is not effective for CNS involvements. ERT targeting CNS and gene therapy are now developing.
To penetrate BBB, transcytosis with insulin and transferrin receptors are used. Ex vivo gene therapy using lentiviral vectors and in vivo gene therapy using adeno-associated viral vectors are developing.
Mucopolysaccharidoses (MPS) are congenital deficiency of lysosomal enzymes responsible for degradation of glycosaminoglycans (GAG). In MPSI and MPSII, dermatan sulfate(DS) and heparan sulfate(HS) accumulate in lysosome. In MPSVI, MPSIII, and MPSIV, DS, HS, and keratin sulfate(KS) accumulate, respectively. Mental retardation and regression are observed in MPSI, II, and III, suggesting accumulated HS in CNS is neurotoxic. Enzyme replacement therapy (ERT) is available in MPSI, II, IVA, and VI, but is not effective for CNS involvements. ERT targeting CNS and gene therapy are now developing.
To penetrate BBB, transcytosis with insulin and transferrin receptors are used. Ex vivo gene therapy using lentiviral vectors and in vivo gene therapy using adeno-associated viral vectors are developing.