Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

General Research Article

Effects of Trehalose Administration in Patients with Mucopolysaccharidosis Type III

Author(s): Moein Mobini, Shabnam Radbakhsh, Francyne Kubaski, Peyman Eshraghi, Saba Vakili, Rahim Vakili, Mitra Abbasifard, Tannaz Jamialahmadi, Omid Rajabi, Seyed Ahmad Emami, Zahra Tayarani-Najaran, Manfredi Rizzo, Ali H. Eid, Maciej Banach and Amirhossein Sahebkar*

Volume 31, Issue 20, 2024

Published on: 21 June, 2023

Page: [3033 - 3042] Pages: 10

DOI: 10.2174/0929867330666230406102555

Price: $65

Open Access Journals Promotions 2
Abstract

Background and Aim: Mucopolysaccharidosis type III (MPS III) is a rare autosomal recessive lysosomal storage disease (LSD) caused by a deficiency of lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs), mainly in the central nervous system. Trehalose has been proposed as a potential therapeutic agent to attenuate neuropathology in MPS III. We conducted a single- arm, open-label study to evaluate the efficacy of trehalose treatment in patients with MPS IIIA and MPS IIIB.

Methods: Five patients with MPS III were enrolled. Trehalose was administrated intravenously (15 g/week) for 12 weeks. Health-related quality of life and cognitive function, serum biomarkers, liver, spleen, and lung imaging were assessed to evaluate trehalose efficacy at baseline and trial end (week 12).

Results: TNO-AZL Preschool children Quality of Life (TAPQOL) scores increased in all patients, and the mean scores for quality of life were increased after the intervention. Serum GAG levels were reduced in all treated patients (however, the differences were not statistically significant). Alanine aminotransferase (ALT) levels were reduced in all patients post-treatment (p=0.0039). The mean levels of aspartate transaminase (AST) were also decreased after 12 weeks of treatment with Trehalose. Decreased serum pro-oxidant-antioxidant balance and increased GPX activity were observed at the end of the study. Decreases in mean splenic length were observed, whereas the liver volume did not change.

Conclusion: Improvements in health-related quality of life and serum biomarkers (GAGs, liver aminotransferase levels, antioxidant status), as well as liver and spleen size, were found following 3 months of trehalose administration in patients with MPS IIIA and MPS IIIB.

Keywords: Lysosomal storage disease (LSD), mucopolysaccharidosis IIIA, mucopolysaccharidosis IIIB, sanfilippo syndrome, trehalose, aspartate transaminase (AST).

« Previous
[1]
Sun, A. Lysosomal storage disease overview. Ann. Transl. Med., 2018, 6(24), 476..
[http://dx.doi.org/10.21037/atm.2018.11.39] [PMID: 30740407]
[2]
Parenti, G.; Andria, G.; Ballabio, A. Lysosomal storage diseases: From pathophysiology to therapy. Annu. Rev. Med., 2015, 66(1), 471-486.
[http://dx.doi.org/10.1146/annurev-med-122313-085916] [PMID: 25587658]
[3]
Andrade, F.; Aldámiz-Echevarría, L.; Llarena, M.; Couce, M.L. Sanfilippo syndrome: Overall review. Pediatr Int, 2015, 57(3), 331-338.
[http://dx.doi.org/10.1111/ped.12636] [PMID: 25851924]
[4]
Kresse, H. Mucopolysaccharidosis III A (Sanfilippo A disease): Deficiency of a heparin sulfamidase in skin fibroblasts and leucocytes. Biochem. Biophys. Res. Commun., 1973, 54(3), 1111-1118.
[http://dx.doi.org/10.1016/0006-291X(73)90807-3] [PMID: 4201808]
[5]
von Figura, K. Human alpha-N-acetylglucosaminidase. 1. Purification and properties. Eur. J. Biochem., 1977, 80(2), 523-533.
[PMID: 411658]
[6]
Fedele, A. Sanfilippo syndrome: Causes, consequences, and treatments. Appl. Clin. Genet., 2015, 8, 269-281.
[http://dx.doi.org/10.2147/TACG.S57672] [PMID: 26648750]
[7]
Benetó, N.; Vilageliu, L.; Grinberg, D.; Canals, I. Sanfilippo syndrome: Molecular basis, disease models and therapeutic approaches. Int. J. Mol. Sci., 2020, 21(21), 7819.
[http://dx.doi.org/10.3390/ijms21217819] [PMID: 33105639]
[8]
Gaffke, L.; Pierzynowska, K.; Piotrowska, E.; Węgrzyn, G. How close are we to therapies for Sanfilippo disease? Metab. Brain Dis., 2018, 33(1), 1-10.
[http://dx.doi.org/10.1007/s11011-017-0111-4] [PMID: 28921412]
[9]
Luyckx, J.; Baudouin, C. Trehalose: An intriguing disaccharide with potential for medical application in ophthalmology. Clin. Ophthalmol., 2011, 5, 577-581.
[PMID: 21654884]
[10]
Colaco, C.; Roser, B. Trehalose-a multifunctional additive for food preservation. Food Packaging and Preservation, 1994, 123-140.
[http://dx.doi.org/10.1007/978-1-4615-2173-0_7]
[11]
Emanuele, E. Can trehalose prevent neurodegeneration? Insights from experimental studies. Curr. Drug Targets, 2014, 15(5), 551-557.
[http://dx.doi.org/10.2174/1389450115666140225104705] [PMID: 24568549]
[12]
Hosseinpour-Moghaddam, K., Caraglia, M., & Sahebkar, A. Autophagy induction by trehalose: Molecular mechanisms and therapeutic impacts. J. Cell. Physiol.,2018233(9), 6524–6543.
[http://dx.doi.org/10.1002/jcp.26583]
[13]
Sahebkar, A.; Khalifeh, M.; Barreto, G.E. Therapeutic potential of trehalose in neurodegenerative diseases: The knowns and unknowns. Neural Regen. Res., 2021, 16(10), 2026-2027.
[http://dx.doi.org/10.4103/1673-5374.308085] [PMID: 33642389]
[14]
Khalifeh, M.; Barreto, G.E.; Sahebkar, A. Trehalose as a promising therapeutic candidate for the treatment of Parkinson’s disease. Br. J. Pharmacol., 2019, 176(9), 1173-1189.
[http://dx.doi.org/10.1111/bph.14623] [PMID: 30767205]
[15]
Khalifeh, M.; Read, M.I.; Barreto, G.E.; Sahebkar, A. Trehalose against Alzheimer’s disease: Insights into a potential therapy. BioEssays, 2020, 42(8), 1900195.
[http://dx.doi.org/10.1002/bies.201900195] [PMID: 32519387]
[16]
Parkinson-Lawrence, E.J.; Shandala, T.; Prodoehl, M.; Plew, R.; Borlace, G.N.; Brooks, D.A. Lysosomal storage disease: Revealing lysosomal function and physiology. Physiology, 2010, 25(2), 102-115.
[http://dx.doi.org/10.1152/physiol.00041.2009] [PMID: 20430954]
[17]
a) Rusmini, P.; Cortese, K.; Crippa, V.; Cristofani, R.; Cicardi, M.E.; Ferrari, V.; Vezzoli, G.; Tedesco, B.; Meroni, M.; Messi, E.; Piccolella, M.; Galbiati, M.; Garrè, M.; Morelli, E.; Vaccari, T.; Poletti, A. Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration. Autophagy, 2019, 15(4), 631-651.
[http://dx.doi.org/10.1080/15548627.2018.1535292] [PMID: 30335591];
b) Mobini, M.; Radbakhsh, S.; Kubaski, F.; Eshraghi, P.; Vakili, S.; Vakili, R.; Khalili, M.; Varesvazirian, M.; Jamialahmadi, T.; Alamdaran, S.; Sayedi, S.; Rajabi, O.; Emami, S.; Reiner, Ž.; Sahebkar, A. Impact of intravenous trehalose administration in patients with niemann–pick disease types A and B. J. Clin. Med., 2022, 11(1), 247.
[http://dx.doi.org/10.3390/jcm11010247] [PMID: 35011993]
[18]
Lotfi, P.; Tse, D.Y.; Di Ronza, A.; Seymour, M.L.; Martano, G.; Cooper, J.D.; Pereira, F.A.; Passafaro, M.; Wu, S.M.; Sardiello, M. Trehalose reduces retinal degeneration, neuroinflammation and storage burden caused by a lysosomal hydrolase deficiency. Autophagy, 2018, 14(8), 1419-1434.
[http://dx.doi.org/10.1080/15548627.2018.1474313] [PMID: 29916295]
[19]
Bunge, E.M.; Essink-Bot, M-L.; Kobussen, M.P.; van Suijlekom-Smit, L.W.; Moll, H.A.; Raat, H. Reliability and validity of health status measurement by the TAPQOL. Arch. Dis. Child., 2005, 90(4), 351-358.
[http://dx.doi.org/10.1136/adc.2003.048645] [PMID: 15781921]
[20]
Kubaski, F.; Mason, R.W.; Nakatomi, A.; Shintaku, H.; Xie, L.; van Vlies, N.N.; Church, H.; Giugliani, R.; Kobayashi, H.; Yamaguchi, S.; Suzuki, Y.; Orii, T.; Fukao, T.; Montaño, A.M.; Tomatsu, S. Newborn screening for mucopolysaccharidoses: A pilot study of measurement of glycosaminoglycans by tandem mass spectrometry. J. Inherit. Metab. Dis., 2017, 40(1), 151-158.
[http://dx.doi.org/10.1007/s10545-016-9981-6] [PMID: 27718145]
[21]
Khan, S.A.; Mason, R.W.; Giugliani, R.; Orii, K.; Fukao, T.; Suzuki, Y.; Yamaguchi, S.; Kobayashi, H.; Orii, T.; Tomatsu, S. Glycosaminoglycans analysis in blood and urine of patients with mucopolysaccharidosis. Mol. Genet. Metab., 2018, 125(1-2), 44-52.
[http://dx.doi.org/10.1016/j.ymgme.2018.04.011] [PMID: 29779903]
[22]
Ghayour-Mobarhan, M.; Alamdari, D.H.; Moohebati, M.; Sahebkar, A.; Nematy, M.; Safarian, M.; Azimi-Nezhad, M.; Reza Parizadeh, S.M.; Tavallaie, S.; Koliakos, G.; Ferns, G. Determination of prooxidant--antioxidant balance after acute coronary syndrome using a rapid assay: A pilot study. Angiology, 2009, 60(6), 657-662.
[http://dx.doi.org/10.1177/0003319709333868] [PMID: 19398426]
[23]
Wagner, V.F.; Northrup, H. Mucopolysaccharidosis Type III. In: GeneReviews(®); Adam, M.P.; Ardinger, H.H.; Pagon, R.A.; Wallace, S.E.; Bean, L.J.H.; Mirzaa, G., Eds.; Seattle (WA): University of Washington, Seattle, 1993.
[24]
de Ruijter, J.; Valstar, M.J.; Wijburg, F.A. Mucopolysaccharidosis type III (Sanfilippo Syndrome): Emerging treatment strategies. Curr. Pharm. Biotechnol., 2011, 12(6), 923-930.
[http://dx.doi.org/10.2174/138920111795542651] [PMID: 21235449]
[25]
Elbein, A.D.; Pan, Y.T.; Pastuszak, I.; Carroll, D. New insights on trehalose: A multifunctional molecule. Glycobiology, 2003, 13(4), 17R-27.
[http://dx.doi.org/10.1093/glycob/cwg047] [PMID: 12626396]
[26]
Jamialahmadi, T.; Emami, F.; Bagheri, R.K.; Alimi, H.; Bioletto, F.; Bo, S.; Aminzadeh, B.; Ansari, M.A.; Ehsani, F.; Rajabi, O.; Ganjali, S.; Banach, M.; Sahebkar, A. The effect of trehalose administration on vascular inflammation in patients with coronary artery disease. Biomed. Pharmacother., 2022, 147, 112632.
[http://dx.doi.org/10.1016/j.biopha.2022.112632] [PMID: 35045351]
[27]
Zaltzman, R.; Elyoseph, Z.; Lev, N.; Gordon, C.R. Trehalose in machado-joseph disease: Safety, tolerability, and efficacy. Cerebellum, 2020, 19(5), 672-679.
[http://dx.doi.org/10.1007/s12311-020-01150-6] [PMID: 32514820]
[28]
Sato, S.; Okamoto, K.; Minami, R.; Kohri, H.; Yamamoto, S. Trehalose can be used as a parenteral saccharide source in rabbits. J. Nutr., 1999, 129(1), 158-164.
[http://dx.doi.org/10.1093/jn/129.1.158] [PMID: 9915893]
[29]
Sweeney, P.; Park, H.; Baumann, M.; Dunlop, J.; Frydman, J.; Kopito, R.; McCampbell, A.; Leblanc, G.; Venkateswaran, A.; Nurmi, A.; Hodgson, R. Protein misfolding in neurodegenerative diseases: Implications and strategies. Transl. Neurodegener., 2017, 6(1), 6.
[http://dx.doi.org/10.1186/s40035-017-0077-5] [PMID: 28293421]
[30]
Cotrina, E.Y.; Santos, L.M.; Rivas, J.; Blasi, D.; Leite, J.P.; Liz, M.A. Targeting transthyretin in Alzheimer's disease: Drug discovery of small-molecule chaperones as disease-modifying drug candidates for Alzheimer's disease. Eur J Med Chem., 2021, 226, 113847.
[http://dx.doi.org/10.1016/j.ejmech.2021.113847]
[31]
Rivero-Ríos, P.; Madero-Pérez, J.; Fernández, B.; Hilfiker, S. Targeting the autophagy/lysosomal degradation pathway in parkinsons disease. Curr. Neuropharmacol., 2016, 14(3), 238-249.
[http://dx.doi.org/10.2174/1570159X13666151030103027] [PMID: 26517050]
[32]
Tapia, H.; Koshland, D.E. Trehalose is a versatile and long-lived chaperone for desiccation tolerance. Curr. Biol., 2014, 24(23), 2758-2766.
[http://dx.doi.org/10.1016/j.cub.2014.10.005] [PMID: 25456447]
[33]
Chen, X.; Li, M.; Li, L.; Xu, S.; Huang, D.; Ju, M.; Huang, J.; Chen, K.; Gu, H. Trehalose, sucrose and raffinose are novel activators of autophagy in human keratinocytes through an mTOR-independent pathway. Sci. Rep., 2016, 6(1), 28423.
[http://dx.doi.org/10.1038/srep28423] [PMID: 27328819]
[34]
Zhang, Y.; Higgins, C.B.; Mayer, A.L.; Mysorekar, I.U.; Razani, B.; Graham, M.J.; Hruz, P.W.; DeBosch, B.J. TFEB-dependent induction of thermogenesis by the hepatocyte SLC2A inhibitor trehalose. Autophagy, 2018, 14(11), 1959-1975.
[http://dx.doi.org/10.1080/15548627.2018.1493044] [PMID: 29996716]
[35]
Wang, Q.; Ren, J. mTOR-Independent autophagy inducer trehalose rescues against insulin resistance-induced myocardial contractile anomalies: Role of p38 MAPK and Foxo1. Pharmacol. Res., 2016, 111, 357-373.
[http://dx.doi.org/10.1016/j.phrs.2016.06.024] [PMID: 27363949]
[36]
Evans, T.D.; Jeong, S.J.; Zhang, X.; Sergin, I.; Razani, B. TFEB and trehalose drive the macrophage autophagy-lysosome system to protect against atherosclerosis. Autophagy, 2018, 14(4), 724-726.
[http://dx.doi.org/10.1080/15548627.2018.1434373] [PMID: 29394113]
[37]
Trudel, S.; Trécherel, E.; Gomila, C.; Peltier, M.; Aubignat, M.; Gubler, B.; Morlière, P.; Heard, J.M.; Ausseil, J. Oxidative stress is independent of inflammation in the neurodegenerative sanfilippo syndrome type B. J. Neurosci. Res., 2015, 93(3), 424-432.
[http://dx.doi.org/10.1002/jnr.23497] [PMID: 25332157]
[38]
Wei, H.; Kim, S.J.; Zhang, Z.; Tsai, P.C.; Wisniewski, K.E.; Mukherjee, A.B. ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones. Hum. Mol. Genet., 2008, 17(4), 469-477.
[http://dx.doi.org/10.1093/hmg/ddm324] [PMID: 17989065]
[39]
Mizunoe, Y.; Kobayashi, M.; Sudo, Y.; Watanabe, S.; Yasukawa, H.; Natori, D.; Hoshino, A.; Negishi, A.; Okita, N.; Komatsu, M.; Higami, Y. Trehalose protects against oxidative stress by regulating the Keap1–Nrf2 and autophagy pathways. Redox Biol., 2018, 15, 115-124.
[http://dx.doi.org/10.1016/j.redox.2017.09.007] [PMID: 29241092]
[40]
Sun, L.; Zhao, Q.; Xiao, Y.; Liu, X.; Li, Y.; Zhang, J.; Pan, J.; Zhang, Z. Trehalose targets Nrf2 signal to alleviate d-galactose induced aging and improve behavioral ability. Biochem. Biophys. Res. Commun., 2020, 521(1), 113-119.
[http://dx.doi.org/10.1016/j.bbrc.2019.10.088] [PMID: 31630800]
[41]
Lin, C.F.; Kuo, Y.T.; Chen, T.Y.; Chien, C.T. Quercetin-rich guava (Psidium guajava) juice in combination with trehalose reduces autophagy, apoptosis and pyroptosis formation in the kidney and pancreas of type II diabetic rats. Molecules, 2016, 21(3), 334.
[http://dx.doi.org/10.3390/molecules21030334] [PMID: 26978332]
[42]
Krawiec, P.; Pac-Kożuchowska, E.; Mełges, B.; Mroczkowska-Juchkiewicz, A.; Skomra, S.; Pawłowska-Kamieniak, A.; Kominek, K. From hypertransaminasemia to mucopolysaccharidosis IIIA. Ital. J. Pediatr., 2014, 40(1), 97.
[http://dx.doi.org/10.1186/s13052-014-0097-z] [PMID: 25439061]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy