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References
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78 Kwiatek, M.A., Roman, S., Fareeduddin, A. etal. (2011). Alimentary Pharmacology
& Therapeutics 34: 59–66.
79 Cunha, L. and Grenha, A. (2016). Marine Drugs 14: 42.
80 Yegappan, R., Selvaprithiviraj, V., Amirthalingam, S., and Jayakumar, R. (2018).
Carbohydrate Polymers 198: 385–400.
81 Ale, M.T. and Meyer, A.S. (2013). RSC Advances 3: 8131–8141.
82 Aronson, J.K. (ed.) (2016). Dextrans. In: Meyler’s Side Effects of Drugs, 893–898.
Elsevier, Oxford.
83 Sobolewski, K., Radparvar, S., Wong, C., and Johnston, J. (2018). A Worldwide
Yearly Survey of New Data in Adverse Drug Reactions, S. D. B. T.S. E. of D. A. Ray,
vol. 40, 415–429. Elsevier.
84 von ZurMühlen, B., Lundgren, T., Bayman, L. etal. (2019). Transplantation 103:
630–637.
85 Tassa, C., Shaw, S.Y., and Weissleder, R. (2011). Accounts of Chemical Research 44:
842–852.
86 Coltelli, M.B., Danti, S., De Clerck, K. etal. (2020). Journal of Functional
Biomaterials 11: 20.
87 Petersen, N. and Gatenholm, P. (2011). Applied Microbiology and Biotechnology 91:
1277–1286.
88 Moscovici, M. (2015). Frontiers in Microbiology 6: 1012.
89 Osmałek, T., Froelich, A., and Tasarek, S. (2014). International Journal of
Pharmaceutics 466: 328–340.
90 Czaja, W.K., Young, D.J., Kawecki, M., and Brown, R.M.J. (2007).
Biomacromolecules 8: 1–12.
91 Finn Madsen, Frédéric Liot. USE OF HIGH ACYL GELLAN IN WHIPPING
CREAM. WO2014184134 (2014).
92 J. Gupta, R. Rathour, K. Medhi, B. Tyagi and I. S. Thakur, eds. R. P. Kumar,
E. Gnansounou, J. K. Raman and G. B. T.R. B. R. for S. E. and B. Baskar,
Academic Press, 2020, pp. 51–85.
93 Zhang, J., Xia, W., Liu, P. etal. (2010). Marine Drugs 8: 1962–1987.
94 Aziz, M.A., Cabral, J.D., Brooks, H.J.L. etal. (2012). Antimicrobial Agents and
Chemotherapy 56: 280–287.
95 M. S. Islam, M. S. Rahman, T. Ahmed, S. Biswas, P. Haque and M. M. Rahman,
eds. S. Gopi, S. Thomas and A. B. T.H. of C. and C. Pius, Elsevier, 2020, pp.
721–759.
96 Erginer, M., Akcay, A., Coskunkan, B. etal. (2016). Carbohydrate Polymers 149:
289–296.
97 Liu, Q., Lyu, Z., Yu, Y. etal. (2017). ACS Applied Materials & Interfaces 9:
11518–11527.
98 Berger, R.P., Dookwah, M., Steet, R., and Dalton, S. (2016). BioEssays 38:
1255–1265.
99 Lu, P., Takai, K., Weaver, V.M., and Werb, Z. Cold Spring Harbor Perspectives in
Biology https://doi.org/10.1101/cshperspect.a005058.
100 Deb, B., Patel, K., Sathe, G., and Kumar, P. (2019). Journal of Clinical Medicine
8: 1303.
241
242
101 Peixoto, A., RelvasSantos, M., Azevedo, R. etal. (2019). Frontiers in
Oncology 9: 380.
102 Mereiter, S., Balmaña, M., Campos, D. etal. (2019). Cancer Cell 36: 6–16.
103 Martins, Á.M., Ramos, C.C., Freitas, D., and Reis, C.A. (2021). Cell 10: 109.
104 MerlPham, J., Basak, T., Knüppel, L. etal. (2019). Matrix Biology Plus 1: 100005.
105 Lecca, M.R., Maag, C., Berger, E.G., and Hennet, T. (2011). Journal of Cellular and
Molecular Medicine 15: 1788–1796.
106 Sorokin, L. (2010). Nature Reviews Immunology 10: 712–723.
107 Maverakis, E., Kim, K., Shimoda, M. etal. (2015). Journal of Autoimmunity
57: 1–13.
108 GrouxDegroote, S., Cavdarli, S., Uchimura, K. etal. (2020). Inflammatory
Disorders, Part A, ed. R. B. T.A. in P. C. and S. B. Donev, vol. 119, 111–156.
Academic Press.
109 Marsico, G., Russo, L., Quondamatteo, F., and Pandit, A. Trends in Cancer https://
doi.org/10.1016/j.trecan.2018.05.009.
110 Rebelo, A.L., Chevalier, M.T., Russo, L., and Pandit, A. Cell Reports Physical
Sciences https://doi.org/10.1016/j.xcrp.2021.100321.
111 Hughes, R.C. (1992). Biochemical Society Transactions 20: 279–284.
112 Tian, E., Hoffman, M.P., and Ten Hagen, K.G. (2012). Nature
Communications 3: 869.
113 Marsico, G., Russo, L., Quondamatteo, F., and Pandit, A. (2018). Trends in Cancer
4: 537–552.
114 Schoelles, K., Snyder, D.L., and Sullivan, N. (2012). Skin Substitutes for Treating
Chronic Wounds. Rockville (MD): Agency for Healthcare Research and Quality
(US) Results https://www.ncbi.nlm.nih.gov/books/NBK248357/.
115 Corduas, F., Lamprou, D.A., and Mancuso, E. (2021). Bio‐Design and
Manufacturing 4: 278–310.
116 Cornwell, K.G., Landsman, A., and James, K.S. (2009). Clinics in Podiatric
Medicine and Surgery 26: 507–523.
117 Cornwell, K.G., Jessee, C.B., and Adelman, D.M. (2020). British Journal of Hospital
Medicine (London, England) 81: 1–10.
118 Liu, W., Wang, X., Su, J. etal. (2021). Frontiers in Bioengineering and
Biotechnology 9: 105.
119 Knopp, U., Christmann, F., Reusche, E., and Sepehrnia, A. (2005). Acta
Neurochirurgica 147: 877–887.
120 Saeki, M., Tanaka, K., Imatani, J. etal. (2018). Injury 49: 766–774.
121 Klein, S., Vykoukal, J., Felthaus, O. etal. (2016). Materials (Basel,
Switzerland) 9: 219.
122 Ezzelarab, M., Ayares, D., and Cooper, D.K.C. (2005). Immunology and Cell Biology
83: 396–404.
123 Du, J. and Yarema, K.J. (2010). Advanced Drug Delivery Reviews 62: 671–682.
124 Adams, A.B., Kim, S.C., Martens, G.R. etal. (2018). Annals of Surgery 268:
564–573.
125 Wong, M.L. and Griffiths, L.G. (2014). Acta Biomaterialia 10: 1806–1816.
References
Данная книга находится в списке для перевода на русский язык сайта https://meduniver.com/
126 C&EN Glob. Enterp. (2021). First GM pigs for allergies. Could xenotransplants be
next? Elie Dolgin. Nature Biotechnology, 39: 397–400.
127 Jayakrishnan, A. and Jameela, S.R. (1996). Biomaterials 17: 471–484.
128 Griffiths, L.G., Choe, L.H., Reardon, K.F. etal. (2008). Biomaterials 29: 3514–3520.
129 Saporito, W.F., Pires, A.C., Cardoso, S.H. etal. (2011). BMC Surgery 11: 37.
130 Riess, F.C., Cramer, E., Hansen, L. etal. (2010). The European Journal of
Cardio‐Thoracic Surgery 37: 145–153.
131 Naso, F., Gandaglia, A., Bottio, T. etal. (2013). Xenotransplantation 20: 252–261.
132 Naso, F., Stefanelli, U., Buratto, E. etal. (2017). Tissue Engineering. Part A 23:
1181–1195.
133 Mahal, L.K., Yarema, K.J., and Bertozzi, C.R. (1997). Science 276: 1125–1128.
134 Dube, D.H. and Bertozzi, C.R. (2003). Current Opinion in Chemical Biology 7:
616–625.
135 Agatemor, C., Buettner, M.J., Ariss, R. etal. (2019). Nature Reviews Chemistry 3:
605–620.
136 Du, J., Agatemor, C., Saeui, C.T. etal. Cell https://doi.org/10.3390/cells10020377.
137 Sampathkumar, S.G., Li, A.V., Jones, M.B. etal. (2006). Nature Chemical Biology
2: 149–152.
138 Gutmann, M., Bechold, J., Seibel, J. etal. (2019). ACS Biomaterials Sciences and
Engineering 5: 215–233.
139 Ruff, S.M., Keller, S., Wieland, D.E. etal. (2017). Acta Biomaterialia 52: 159–170.
140 Nellinger, S., Rapp, M.A., Southan, A. etal. ChemBioChem https://doi.
org/10.1002/cbic.202100266.
243
9
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Carbohydrate-Based Therapeutics forLysosomal
Storage Disorders
Camilla Matassini, Francesca Clemente, and Francesca Cardona
Department of Chemistry “U. Schiff” (DICUS), University of Florence, via della Lastruccia 3-13, 50019 Sesto F.no
(FI), Italy
9.1 An Introduction to Lysosomal Storage
Disorders (LSDs)
Lysosomal Storage Disorders (LSDs) are a group of 70 inherited metabolic
disorders[1] that affect the function of the lysosome, a membranebound organelle
with a key role in processes involved in degrading and recycling cellular waste, cellular signaling, and energy metabolism[2]. LSDs are monogenic disorders caused
by the mutation in a gene encoding for a lysosomal protein (such as lysosomal glycosidases, proteases, integral membrane proteins, transporters, enzyme modifiers,
or activators), resulting in lysosomal failure and subsequent accumulation of non
metabolized substrates. This steady accumulation of substrates in the lysosome, the
“storage,” hence the name of these disorders, ultimately leads to cell dysfunction
and cell death (Figure9.1).
LSDs are considered a class of genetically and clinically heterogeneous disorders,
even though some common clinical features, such as a pediatric onset and the
enlargement of abdominal organs, mainly liver and spleen (visceromegaly), can be
identified. Other frequent symptoms, related to the specific genetic mutation and
the consequent stored substrate, are skeletal dysmorphia, developmental delay, or
other central nervous system (CNS) deficits. Diagnosis of LSDs is based on clinical
symptoms and subsequent confirmation with biochemical and genetic tests, such as
enzymatic dosage and gene sequencing[3]. Unfortunately, especially for the less
severe forms with longer survival, the overlapping clinical features that are not specific for LSDs lead to considerable diagnostic delay and missed cases, while early
diagnosis is a priority for the application of new diseasemodifying therapies.
245
Carbohydrate-Based Therapeutics, First Edition. Edited by Roberto Adamo and Luigi Lay.
© 2024 WILEY-VCH GmbH. Published 2024 by WILEY-VCH GmbH.
Normal
ly
Diseased
Elimination
246
sosome
Breakdown
Recycled
lysosome
Substrate
accumulation
Tissue/organ damage
and
diesease symptoms
Figure9.1 Comparison of a healthy lysosome with a defective one of LSD patients: the
genetic mutation results in lysosome failure, hampering the breakdown and recycling of
macromolecules and leading to tissue and organ dysfunctions with consequent disease
symptoms.
Epidemiology and diagnosis of LSDs, as well as challenges for the screening of carriers, highrisk and newborn populations have been carefully reviewed by Wijburg
and coworkers[4].
Information about the incidence of LSDs is relatively limited. However, although
rare if taken individually (one case per 50 000–250 000individuals), they are common as a group, with an estimated incidence of 1in 5000–5500live births[5]. The
most common LSDs are Fabry, Gaucher, and Pompe diseases (PDs), with up to 2–2.5
cases per 100 000individuals [6]. Moreover, despite a general low occurrence of
individual LSDs, the incidence may be higher in specific ethnicities, such as in the
case of Gaucher disease (GD), for which a frequency of 1 in 500 to 1in 1000 is
observed among Ashkenazi Jews[7].
LSDs related to enzyme deficiencies, which are the focus of this chapter, can be
subclassified according to the stored materials (see Table9.1):
1- Mucopolysaccharidoses (MPS) (such as MPS I, II, III e IVA)
2- Sphingolipidoses (such as Fabry, Niemann–Pick (NP) and GD, GM1 and
GM2gangliosidosis, and Krabbe disease (KD))
3- Glycogen Storage Disorders (namely, Pompe disease)
4- Glycoproteinoses (such as αMannosidosis and Fucosidosis)
Each disease can be in turn classified into different types based on symptoms,
affected organs, and age of onset, such as congenital or infantile (which usually
have the most severe presentation), lateinfantile, juvenile, and adult types.
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Table9.1 Lysosomal storage disorders object ofthis chapter, classified according tothe
stored material: foreach disorder thename(s), thedeficient enzyme, and theapproved
therapy are listed.
Approved
Disease Deficient lysosomal enzyme
therapies
Mucopolysaccharidoses (MPS)
MPS I: Hurler syndrome αiduronidase HSCT, ERT
MPS II: Hunter syndrome Iduronate2sulfatase (IDS) ERT
MPS IIIA: Sanfilippo
Nsulfoglucosamine sulfohydrolase NONE
a
syndrome A
MPS IIIB: Sanfilippo
Nacetylαglucosaminidase (NAGLU) NONE
a
syndrome B
MPS IIIC (Sanfilippo
syndrome)
MPS IIID (Sanfilippo
Acetyl CoA glucosamine
Nacetyltransferase
Nacetylglucosamine6sulfatase NONE
NONE
a
a
syndrome)
MPS IVA: Morquio syndrome N‐acetylgalactosamine6sulfatase
ERT
(GALNS)
MPS IVB (Morquio B
syndrome)
b
MPS VI (Maroteaux–Lamy
βgalactosidase NONE
Arylsulfatase B ERT
a
syndrome)
MPS VII (Sly syndrome) βglucuronidase ERT
MPS IX Hyaluronidase NONE
a
Sphingolipidoses
Fabry disease αgalactosidase A ERT, PCT
Gaucher disease βglucocerebrosidase, also known as
ERT, SRT
acid βglucosidase (GCase)
Niemann–Pick Sphingomyelindegrading enzyme acid
ERT
sphingomyelinase and cholesterol
transport proteins
GM1gangliosidosis βgalactosidase NONE
GM2gagliosidosis: Tay–Sachs
βhexosaminidase NONE
a
a
disease and Sandhoff disease
Krabbe disease Galactosylceramidase HSCT
Glycogen storage disease
Pompe disease αglucosidase ERT
Glycoproteinoses
Fucosidosis αfucosidase NONE
a
αmannosidosis αmannosidase ERT
247
a) “NONE” means that only symptomatic and supportive therapies are provided to patients.
b) Being βgalactosidase the deficient enzyme in MPS IVB, this disorder will be discussed
together with GM1 (Sphingolipidoses section) instead of in the Mucopolysaccharidoses section.
ERT, enzyme replacement therapy; SRT, substrate reduction therapy; PCT, pharmacological
chaperone therapy.
248
9.2 Available Treatments for LSDs: The Role of
Carbohydrate-Based Therapeutics
The promulgation of U.S. Orphan Drug Act (ODA) in 1983, followed by analogous
“orphan” legislation in other countries, undoubtedly stimulated the investments in
novel therapies for rare conditions, including LSDs, that otherwise would not be
profitable due to the small target population[8]. The consequently growing understanding of the pathophysiology of LSDs reached in the last decades, allowed to
identify various potential clinical intervention points, thus developing innovative
therapies, some of which passed all the steps from preclinical stage to regulatory
approval, and they were ultimately made available for patients. The most relevant
therapeutic approaches for LSDs are briefly described below.
The first treatment of an LSD, which showed any success was the hematopoietic
stem cell transplantation (HSCT) in a oneyearold MPS I patient, in 1981[9]. In
particular, the transplanted bone marrowderived cells with normal enzyme levels
were thought to donate enzymes to the patient’s deficient cells[10]. Unfortunately,
this therapy resulted efficient only in MPS I patients younger than nine months of
age, and presents important issues related to donor selection and adverse effects of
transplantation[11, 12]. HSCT is currently the standard care for MPS I younger
patients, despite the high risks of mortality, and it has been also used for other LSDs
without available treatments, such as KD[1].
Recently, gene therapy methods, such as gene replacement, antisense oligonucleotide (ASO) therapies, or gene editing, are also emerging for the treatment of
LSDs[13–15].
In particular, some variants of adenoassociated virus (AAV) resulted in excellent
vectors to deliver the gene encoding the deficient enzymes to cells[16]. Once manufactured for human use, the vector can be directly infused into the bloodstream or
target organs (direct gene transfer) or it can be applied ex‐vivo to stem cells in culture
and subsequently reimplanted into the donor (indirect gene transfer) [1]. These
cuttingedge therapies, all still in clinical trials for very few disorders, seem to be
effective in achieving remission of neurological manifestations. However, the major
drawbacks are related to establishing safe administration regime, the invasive route
of administration, and the difficulty of foreseeing longterm undesired effects[17].
Enzyme replacement therapy (ERT) consists of intravenous infusion of a recombinant wildtype enzyme, which enters the cell through membrane receptors (typically the mannose6phosphate receptor (M6PR)) and replaces the catalytic action
of the mutated lysosomal enzyme[18, 19]. Available since 1996[20], ERT is the only
treatment approved for many LSDs (Table9.1). The main limitations associated
with ERT are its high cost, possible immunologic response, and frequent hospitalization of patients, which have been now partially overcome with domiciliary treatments. In addition, the recombinant enzymes used are not able to cross the
blood–brain barrier (BBB) and reach the CNS, so that ERT lacks efficacy in neuronopathic forms of disorders.
The aim of the substrate reduction therapy (SRT) is to reduce the storage in the
lysosomes of undegraded substrates by using small molecules able to inhibit their
9.2 Available Treatments for LSDs: The Role of Carbohydrate-Based Therapeutics
macological
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biosynthesis[21]. SRT could be in principle developed for all LSDs, but, to date, is
approved for Gaucher and NP diseases only, because, for these glycosphingolipids,
the knowledge of their biosynthetic pathways allowed to identify specific inhibitors
of the enzyme that synthesizes the substrates or one of their precursors.
Although trials in other glycosphingolipids and MPS are ongoing, the limitation
to very few pathologies represents the main drawback of SRT. In addition, SRT has
a slower efficacy than ERT and several side effects or complications, such as diarrhea, flatulence, abdominal pain, or weight loss.
In several LSDs, gene mutations result in lysosomal enzymes prone to a rapid
turnover or with a reduced catalytic activity [22]. However, since the substrate
accumulation occurs when residual enzyme activity decays below a certain threshold, a small improvement in the enzyme activity can be sufficient to slow down the
disease progression and to ameliorate clinical evidence. This is the concept on
which the pharmacological chaperone therapy (PCT) is based: it employs small
molecules (pharmacological chaperones, PCs) able to stabilize the tertiary structure of the mutant enzyme, thus improving its catalytic activity and reducing the
storage in the lysosomes (Figure9.2).
The main advantages of PCs are their lowcost, the oral administration, and the
possibility to cross the BBB exerting their action on the CNS[23].
Several PCs were designed and synthesized based on the structure of the natural
substrate or alternatively identified by highthroughput screening (HTS) studies. To
date, the only PC that reached the drug market is Migalastat (Galafold®, Amicus
249
Lysosome
Golgi
Stabilized
protein
ER
Figure9.2 Cartoon representing the Pharmacological Chaperone (PC) concept. Source:
Reproduced with permission from Boyd etal.[23]. © 2013 American Chemical Society
Publications.
PC
Misfolded
protein
Phar
chaperone (PC)
ERAD
Autophagy
250
Therapeutics)[24, 25] for the treatment of Fabry disease (FD), but many other
compounds showed encouraging results in preclinical studies for the treatment of
other LSDs, including GD, Pompe disease, or gangliosidosis.
Surprisingly, except for cellbased therapies (both the oldest bone marrow transplantation and the emerging gene therapy), the most currently employed treatments, namely ERT, SRT, and PCT, all involve the use of iminosugars, sugar analogs
with a nitrogen replacing the endocyclic oxygen atom[26].
Iminosugars have been isolated from natural sources, including plants and microorganisms, for over 50 years. A great effort for their total synthesis has been pursued
by many researchers all around the world. For their synthesis, which is very challenging due to the presence of several contiguous stereocenters with a welldefined
configuration, both chiral pool strategies and enantioselective syntheses have been
developed[27–33].
Their resemblance to carbohydrates allows them to be recognized by, and interact
with carbohydrate receptors. In particular, iminosugars have been extensively investigated in the last 30 years as glycosidase [34–36] and glycosyltransferase
inhibitors[37–41].
They are more chemically and metabolically stable than their parent sugars, are
highly water soluble, can cross the BBB, and are normally excreted from the body
unmodified. Such properties distinguish them from other small polar molecules
and provide significant advantages for their use as drugs, especially in the treatment
of LSDs.
9.2.1 Enzyme Replacement Therapy (ERT)
In the 1980s the ingestion of plants belonging to the Leguminosae family was considered responsible for inducing lysosomal storage diseases in animals (e.g. swainsona toxicosis [42] or locoweed poisoning[43]) because of their high content of
iminosugars able to inhibit lysosomal glycosidases.
The observation that the endogenous enzyme activity was restored when the
inhibitor was removed[44] suggested that the lysosomal storage caused by the deficient enzyme in human LSD patients could be faced by supplying a natural or
recombinant functional enzyme, thus paving the way for the introduction of
the ERT.
ERT is based on the replacement of the mutated protein with normal protein to
restore its wildtype function. Although initially purified from human tissues, nowadays the deficient enzymes are produced by recombinant DNA technology.
Mammalderived cells, such as Chinese Hamster Ovary (CHO) cells, are the most
widely used platform to produce ERT recombinant enzymes[45].
After their efficacy and safety have been confirmed by clinical trials, to date, there
are 10 approved therapeutic enzymes as ERT for 7LSDs (Table9.1). Nevertheless,
there are some drawbacks related to this therapy, such as immune reactions, low
efficiency of lysosomal targeting, and difficulty reaching CNS. To overcome these
limitations, several strategies have been developed with the aim of increasing the
targeting efficiency and the ability to cross the BBB. Many of these approaches
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