Non-clinical evaluation of a blood-brain barrier-penetrating enzyme for the treatment of mucopolysaccharidosis type I

Kida, Sachiho; Kinoshita, Masafumi; Tanaka, Shingo; Okumura, Miho; Koshimura, Yuri; Morimoto, Hideto

doi:10.1016/j.ymgme.2018.12.205

Cited by 4 publications

(6 citation statements)

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“…Although TAT, as a ligand, induced receptor-mediated endocytosis using the negatively charged heparan sulfate proteoglycans (HSPGs) on the cell surface, HSPGs in the form of receptors are ubiquitously expressed on many types of cells. Interestingly, J-Brain Cargo ® ( Figure 5 ) [ 2 , 29 ], established by JCR Pharmaceuticals (Ashiya, Japan), is a system to deliver drugs into the brain across the BBB via RMT, using ADCs composed of anti-TfR mAb and drugs. This system is used by the drug idursulfase beta ( Figure 5 ), approved in Japan on 23 March 2021 for the treatment of Hunter syndrome [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…RMT is one solution using receptors such as TfR or InsR that are expressed at the apical membrane of the capillary endothelial cells in the BBB. The delivery of cancer drugs into the brain via RMT can be developed using a system similar to J-Brain Cargo ® ( Figure 5 ) [ 2 , 29 ], based on the conjugates of anti-TfR mAb and their cargoes. Moreover, drug delivery methods that can cross the BBB using anti-TfR mAb as a vector were reported widely, although they had not yet been used for brain cancers [ Table 1 ].…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, J-Brain Cargo ® (Figure 5) [2,29], established by JCR Pharmaceuticals (Ashiya, Japan), is a system to deliver drugs into the brain across the BBB via RMT, using ADCs composed of anti-TfR mAb and drugs. This system is used by the drug idursulfase beta (Figure 5), approved in Japan on 23 March 2021 for the treatment of Hunter syndrome [30].…”

Section: Anti-receptor Adcs That Cross the Endothelium Via Rmtmentioning

confidence: 99%

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Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

Tashima

2022

Biomedicines

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Advances in pharmacotherapy have brought extraordinary benefits to humanity. However, unmet medical needs in patients remain, particularly in the treatment of central nervous system (CNS) diseases and cancers. CNS drug delivery into the brain across the endothelium is difficult due to the blood-brain barrier (BBB), which is composed mainly of tight junctions and efflux transporters, such as multiple drug resistance 1 (MDR1) (P-glycoprotein). On the other hand, the development of anti-cancer drugs is a challenging task due to their frequent off-target side effects and the complicated mechanisms of cancer pathogenesis and progression. Brain cancer treatment options are surgery, radiation therapy, and chemotherapy. It is difficult to remove all tumor cells, even by surgical removal after a craniotomy. Accordingly, innovative brain cancer drugs are needed. Currently, antibody (Ab) drugs that show high therapeutic effects are often used clinically. Furthermore, antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan, an anti-HER2 (human epidermal receptor 2) ADC with low-molecular cancer drugs through the suitable linker, have been developed. In the case of trastuzumab deruxtecan, it is internalized into cancer cells across the membrane via receptor-mediated endocytosis. Moreover, it is reported that drug delivery into the brain across the BBB was carried out via receptor-mediated transcytosis (RMT), using anti-receptor Abs as a vector against the transferrin receptor (TfR) or insulin receptor (InsR). Thus, anti-TfR ADCs with cancer drugs are promising brain cancer agents due to their precise distribution and low side effects. In this review, I introduce the implementations and potential of brain cancer drug delivery into the brain across the BBB, based on RMT using ADCs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Anti-receptor Adcs That Cross the Endothelium Via Rmtmentioning

confidence: 99%

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Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

Tashima

2022

Biomedicines

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“…Despite its orphan designation in Japan, which was approved in March 2021, this constitutes a major breakthrough for such platforms, as this proprietary modular platform can be potentially used for brain-targeted delivery for other diseases, such as mucopolysaccharidosis I, which is being evaluated using JR-171, a fusion protein of J-Brain Cargo and α-L-iduronidase (IDUA) [90]. Although its inclusion is on the basis that antibodies are essentially nanomedicines in their own right, it exemplifies the promise of such receptor-mediated delivery systems, with the primary consideration for testing ensuring the model accounts for the inter-species TfR expression disparities (2.5-fold higher in mice brain microvessels) [91].…”

Section: Transferrin (Tfr) Receptor-mediated Transcytosismentioning

confidence: 99%

Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

Lynch

Gobbo

2021

Nanomaterials

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Nanotheranostics constitute a novel drug delivery system approach to improving systemic, brain-targeted delivery of diagnostic imaging agents and pharmacological moieties in one rational carrier platform. While there have been notable successes in this field, currently, the clinical translation of such delivery systems for the treatment of neurological disorders has been limited by the inadequacy of correlating in vitro and in vivo data on blood–brain barrier (BBB) permeation and biocompatibility of nanomaterials. This review aims to identify the most contemporary non-invasive approaches for BBB crossing using nanotheranostics as a novel drug delivery strategy and current non-animal-based models for assessing the safety and efficiency of such formulations. This review will also address current and future directions of select in vitro models for reducing the cumbersome and laborious mandate for testing exclusively in animals. It is hoped these non-animal-based modelling approaches will facilitate researchers in optimising promising multifunctional nanocarriers with a view to accelerating clinical testing and authorisation applications. By rational design and appropriate selection of characterised and validated models, ranging from monolayer cell cultures to organ-on-chip microfluidics, promising nanotheranostic particles with modular and rational design can be screened in high-throughput models with robust predictive power. Thus, this article serves to highlight abbreviated research and development possibilities with clinical translational relevance for developing novel nanomaterial-based neuropharmaceuticals for therapy in CNS disorders. By generating predictive data for prospective nanomedicines using validated in vitro models for supporting clinical applications in lieu of requiring extensive use of in vivo animal models that have notable limitations, it is hoped that there will be a burgeoning in the nanotherapy of CNS disorders by virtue of accelerated lead identification through screening, optimisation through rational design for brain-targeted delivery across the BBB and clinical testing and approval using fewer animals. Additionally, by using models with tissue of human origin, reproducible therapeutically relevant nanomedicine delivery and individualised therapy can be realised.

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“…The enzyme is conjugated with an antibody against a specific receptor and can defeat the BBB by transcytosis via epithelial cells. Clinical trials have been conducted using iduronate 2-sulphatase combined with an anti-human transferrin receptor antibody (J-Brain Cargo ® , JR-141, JCR Pharmaceuticals) [ 28 ] and an anti-insulin receptor antibody (AGT-182, ArmaGen Technologies). The first outcomes of studies with JR-141 showed a positive result in reducing the concentration of HS and DS in the cerebrospinal fluid, urine, and plasma.…”

Section: Introductionmentioning

confidence: 99%

Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities

Zapolnik

Pyrkosz

2021

IJMS

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Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder based on a mutation in the IDS gene that encodes iduronate 2-sulphatase. As a result, there is an accumulation of glycosaminoglycans—heparan sulphate and dermatan sulphate—in almost all body tissues, which leads to their dysfunction. Currently, the primary treatment is enzyme replacement therapy, which improves the course of the disease by reducing somatic symptoms, including hepatomegaly and splenomegaly. The enzyme, however, does not cross the blood–brain barrier, and no improvement in the function of the central nervous system has been observed in patients with the severe form of the disease. An alternative method of treatment that solves typical problems of enzyme replacement therapy is gene therapy, i.e., delivery of the correct gene to target cells through an appropriate vector. Much progress has been made in applying gene therapy for MPS II, from cellular models to human clinical trials. In this article, we briefly present the history and basics of gene therapy and discuss the current state of knowledge about the methods of this therapy in mucopolysaccharidosis type II.

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Non-clinical evaluation of a blood-brain barrier-penetrating enzyme for the treatment of mucopolysaccharidosis type I

Cited by 4 publications

References 0 publications

Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

Advances in Non-Animal Testing Approaches towards Accelerated Clinical Translation of Novel Nanotheranostic Therapeutics for Central Nervous System Disorders

Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities

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