Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses
Although the advent of enzyme replacement therapy (ERT) for mucopolysaccharidoses (MPS) has paved the way for the treatment for these hereditary disorders, the blood brain barrier (BBB) has prevented patients with MPS involving the central nervous system (CNS) from benefitting from ERT. Therefore, f...
Main Authors: | , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2020-01-01
|
Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/21/2/400 |
id |
doaj-2e97b68ce17d473f9986853ea299b1be |
---|---|
record_format |
Article |
spelling |
doaj-2e97b68ce17d473f9986853ea299b1be2020-11-25T02:05:45ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-01-0121240010.3390/ijms21020400ijms21020400Novel Enzyme Replacement Therapies for Neuropathic MucopolysaccharidosesYuji Sato0Torayuki Okuyama1Research and Development, JCR Pharmaceuticals, Hyogo 659-0021, JapanCentre for Lysosomal Storage Diseases, National Centre for Child Health and Development, Tokyo 157-8535, JapanAlthough the advent of enzyme replacement therapy (ERT) for mucopolysaccharidoses (MPS) has paved the way for the treatment for these hereditary disorders, the blood brain barrier (BBB) has prevented patients with MPS involving the central nervous system (CNS) from benefitting from ERT. Therefore, finding ways to increase drug delivery into the brain across the BBB remains a crucial challenge for researchers and clinicians in the field. Attempts have been made to boost brain uptake of enzymes by targeting various receptors (e.g., insulin and transferrin), and several other administration routes have also been tested. This review summarizes the available information on clinical trials (completed, ongoing, and planned) of novel therapeutic agents with efficacy against CNS symptoms in neuropathic MPS and also discusses the common associated challenges and pitfalls, some of which may help elucidate the pathogenesis of the neurodegeneration leading to the manifold CNS symptoms. A summary of current knowledge pertaining to the neuropathological progression and resultant neuropsychiatric manifestations is also provided, because it should be useful to ERT researchers looking for better approaches to treating CNS lesions in MPS.https://www.mdpi.com/1422-0067/21/2/400neuropathic mucopolysaccharidosisneurodegenerationenzyme replacement therapyblood brain barriertransferrin receptorinsulin receptortranscytosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuji Sato Torayuki Okuyama |
spellingShingle |
Yuji Sato Torayuki Okuyama Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses International Journal of Molecular Sciences neuropathic mucopolysaccharidosis neurodegeneration enzyme replacement therapy blood brain barrier transferrin receptor insulin receptor transcytosis |
author_facet |
Yuji Sato Torayuki Okuyama |
author_sort |
Yuji Sato |
title |
Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses |
title_short |
Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses |
title_full |
Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses |
title_fullStr |
Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses |
title_full_unstemmed |
Novel Enzyme Replacement Therapies for Neuropathic Mucopolysaccharidoses |
title_sort |
novel enzyme replacement therapies for neuropathic mucopolysaccharidoses |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-01-01 |
description |
Although the advent of enzyme replacement therapy (ERT) for mucopolysaccharidoses (MPS) has paved the way for the treatment for these hereditary disorders, the blood brain barrier (BBB) has prevented patients with MPS involving the central nervous system (CNS) from benefitting from ERT. Therefore, finding ways to increase drug delivery into the brain across the BBB remains a crucial challenge for researchers and clinicians in the field. Attempts have been made to boost brain uptake of enzymes by targeting various receptors (e.g., insulin and transferrin), and several other administration routes have also been tested. This review summarizes the available information on clinical trials (completed, ongoing, and planned) of novel therapeutic agents with efficacy against CNS symptoms in neuropathic MPS and also discusses the common associated challenges and pitfalls, some of which may help elucidate the pathogenesis of the neurodegeneration leading to the manifold CNS symptoms. A summary of current knowledge pertaining to the neuropathological progression and resultant neuropsychiatric manifestations is also provided, because it should be useful to ERT researchers looking for better approaches to treating CNS lesions in MPS. |
topic |
neuropathic mucopolysaccharidosis neurodegeneration enzyme replacement therapy blood brain barrier transferrin receptor insulin receptor transcytosis |
url |
https://www.mdpi.com/1422-0067/21/2/400 |
work_keys_str_mv |
AT yujisato novelenzymereplacementtherapiesforneuropathicmucopolysaccharidoses AT torayukiokuyama novelenzymereplacementtherapiesforneuropathicmucopolysaccharidoses |
_version_ |
1724937110686793728 |