New Advanced Strategies for the Treatment of Lysosomal Diseases Affecting the  Central Nervous System

Maria    R.   Gigliobianco; Piera       Di Martino; Siyuan       Deng; Cristina       Casadidio; Roberta       Censi
Abstract

Lysosomal Storage Disorders (LSDs), also known as lysosomal diseases (LDs) are a group of serious genetic diseases characterized by not only the accumulation of non-catabolized compounds in the lysosomes due to the deficiency of specific enzymes which usually eliminate these compounds, but also by trafficking, calcium changes and acidification. LDs mainly affect the central nervous system (CNS), which is difficult to reach for drugs and biological molecules due to the presence of the blood-brain barrier (BBB). While some therapies have proven highly effective in treating peripheral disorders in LD patients, they fail to overcome the BBB. Researchers have developed many strategies to circumvent this problem, for example, by creating carriers for enzyme delivery, which improve the enzyme’s half-life and the overexpression of receptors and transporters in the luminal or abluminal membranes of the BBB. This review aims to successfully examine the strategies developed during the last decade for the treatment of LDs, which mainly affect the CNS. Among the LD treatments, enzyme-replacement therapy (ERT) and gene therapy have proven effective, while nanoparticle, fusion protein, and small molecule-based therapies seem to offer considerable promise to treat the CNS pathology. This work also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of LDs. Polymeric nanoparticles and liposomes are explored from their technological point of view and for the most relevant preclinical studies showing that they are excellent choices to protect active molecules and transport them through the BBB to target specific brain substrates for the treatment of LDs.
Keywords: Lysosomes, ERT, gene therapy, nanoparticle-based therapy, polymeric nanoparticles, liposomes, blood-brain barrier, active targeting.
[1] 
Vitner EB, Futerman AH, Platt N. Innate immune responses in the brain of sphingolipid lysosomal storage diseases. Biol Chem  2015; 396(6-7): 659-67.
[http://dx.doi.org/10.1515/hsz-2014-0301] [PMID:  25720063] 
[2] 
Deng H, Xiu X, Jankovic J. Genetic convergence of Parkinson’s disease and lysosomal storage disorders. Mol Neurobiol  2015; 51(3): 1554-68.
[http://dx.doi.org/10.1007/s12035-014-8832-4] [PMID:  25099932] 
[3] 
Futerman AH, van Meer G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol  2004; 5(7): 554-65.
[http://dx.doi.org/10.1038/nrm1423] [PMID:  15232573] 
[4] 
Boustany RM. Lysosomal storage diseases--the horizon expands. Nat Rev Neurol  2013; 9(10): 583-98.
[http://dx.doi.org/10.1038/nrneurol.2013.163] [PMID:  23938739] 
[5] 
Parenti G, Andria G, Ballabio A. Lysosomal storage diseases: From pathophysiology to therapy. Annu Rev Med  2015; 66: 471-86.
[http://dx.doi.org/10.1146/annurev-med-122313-085916] [PMID:  25587658] 
[6] 
Penati R, Fumagalli F, Calbi V, Bernardo ME, Aiuti A. Gene therapy for lysosomal storage disorders: Recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I. J Inherit Metab Dis  2017; 40(4): 543-54.
[http://dx.doi.org/10.1007/s10545-017-0052-4] [PMID:  28560469] 
[7] 
Coutinho MF, Alves S. From rare to common and back again: 60years of lysosomal dysfunction. Mol Genet Metab  2016; 117(2): 53-65.
[http://dx.doi.org/10.1016/j.ymgme.2015.08.008] [PMID:  26422115] 
[8] 
Germain DP. [Lysosomes and lysosomal storage diseases] J Soc Biol  2002; 196(2): 127-34.
[http://dx.doi.org/10.1051/jbio/2002196020127] [PMID:  12360741] 
[9] 
Bruni S, Lochi L, Incerti C, et al. Update on treatment of lysosomal storage diseases  Acta Myologica 2007; 87-92.
[10] 
Futerman AH, van Meer G. The cell biology of lysosomal storage disorders. Nat Rev Mol Cell Biol  2004; 5(7): 554-65.
[http://dx.doi.org/10.1038/nrm1423] [PMID:  15232573] 
[11] 
Martín-Banderas L, Holgado MA, Durán-Lobato M, Infante JJ, Álvarez-Fuentes J, Fernández-Arévalo M. Role of Nanotechnology for Enzyme Replacement Therapy in Lysosomal Diseases. A Focus on Gaucher’s Disease. Curr Med Chem  2016; 23(9): 929-52.
[http://dx.doi.org/10.2174/0929867323666160210130608] [PMID:  26860997] 
[12] 
Seregin SS, Amalfitano A. Gene therapy for lysosomal storage diseases: Progress, challenges and future prospects. Curr Pharm Des  2011; 17(24): 2558-74.
[http://dx.doi.org/10.2174/138161211797247578] [PMID:  21774776] 
[13] 
Saftig P.  Physiology of the lysosome.Fabry Disease: Perspectives from 5 Years of FOS. Oxford: Oxford PharmaGenesis 2006.
[14] 
Kelly JM, Bradbury A, Martin DR, Byrne ME. Emerging therapies for neuropathic lysosomal storage disorders. Prog Neurobiol  2017; 152: 166-80.
[http://dx.doi.org/10.1016/j.pneurobio.2016.10.002] [PMID:  27725193] 
[15] 
Matern D, Oglesbee D, Tortorelli S. Newborn Screening for Lysosomal Storage Diseases: A Concise Review of the Literature on Screening Methods, Therapeutic Possibilities and Regional Programs. Dev Disabil Res Rev  2013; 17: 247-53.
[http://dx.doi.org/10.1002/ddrr.1117] [PMID:  23798012] 
[16] 
Sheth JJ, Sheth FJ, Oza NJ, Gambhir PS, Dave UP, Shah RC. Plasma chitotriosidase activity in children with lysosomal storage disorders. Indian J Pediatr  2010; 77(2): 203-5.
[http://dx.doi.org/10.1007/s12098-009-0249-0] [PMID:  19936666] 
[17] 
Muro S. Strategies for delivery of therapeutics into the central nervous system for treatment of lysosomal storage disorders. Drug Deliv Transl Res  2012; 2(3): 169-86.
[http://dx.doi.org/10.1007/s13346-012-0072-4] [PMID:  24688886] 
[18] 
Bellettato CM, Scarpa M. Pathophysiology of neuropathic lysosomal storage disorders. J Inherit Metab Dis  2010; 33(4): 347-62.
[http://dx.doi.org/10.1007/s10545-010-9075-9] [PMID:  20429032] 
[19] 
Mahta AWB. Lysosomal storage disorders: Practical guide. Wiley 2012.
[20] 
Li M. Enzyme Replacement Therapy: A Review and Its Role in Treating Lysosomal Storage Diseases. Pediatr Ann  2018; 47(5): E191-7.
[http://dx.doi.org/10.3928/19382359-20180424-01] [PMID:  29750286] 
[21] 
Schielen PCJI, Kemper EA, Gelb MH. Newborn screening for lysosomal storage diseases: A concise review of the literature on screening methods, therapeutic possibilities and regional programs. Int J Neonatal Screen  2017; 3(2): 6.
[http://dx.doi.org/10.3390/ijns3020006] [PMID:  28730181] 
[22] 
Ohira M, Okuyama T, Mashima R. Quantification of 11 enzyme activities of lysosomal storage disorders using liquid chromatography-tandem mass spectrometry. Mol Genet Metab Rep  2018; 17: 9-15.
[http://dx.doi.org/10.1016/j.ymgmr.2018.08.005] [PMID:  30211004] 
[23] 
Whiteman DA, Kimura A. Development of idursulfase therapy for mucopolysaccharidosis type II (Hunter syndrome): The past, the present and the future. Drug Des Devel Ther  2017; 11: 2467-80.
[http://dx.doi.org/10.2147/DDDT.S139601] [PMID:  28860717] 
[24] 
Journet A, Chapel A, Kieffer S, Roux F, Garin J. Proteomic analysis of human lysosomes: Application to monocytic and breast cancer cells. Proteomics  2002; 2(8): 1026-40.
[http://dx.doi.org/10.1002/1615-9861(200208)2:8<1026:AID-PROT1026>3.0.CO;2-I] [PMID:  12203898] 
[25] 
Bagshaw RD, Mahuran DJ, Callahan JW. Lysosomal membrane proteomics and biogenesis of lysosomes. Mol Neurobiol  2005; 32(1): 27-41.
[http://dx.doi.org/10.1385/MN:32:1:027] [PMID:  16077181] 
[26] 
Pacini F.  Best practice & research clinical endocrinology & metabolism. Thyroid nodules and cancer. Preface. Best Pract Res Clin Endocrinol Metab 2008; 22(6): Vii.
[http://dx.doi.org/10.1016/j.beem.2008.11.001] [PMID: 19041820] 
[27] 
Xiong J, Zhu MX. Regulation of lysosomal ion homeostasis by channels and transporters. Sci China Life Sci  2016; 59(8): 777-91.
[http://dx.doi.org/10.1007/s11427-016-5090-x] [PMID:  27430889] 
[28] 
Eskelinen EL, Tanaka Y, Saftig P. At the acidic edge: Emerging functions for lysosomal membrane proteins. Trends Cell Biol  2003; 13(3): 137-45.
[http://dx.doi.org/10.1016/S0962-8924(03)00005-9] [PMID:  12628346] 
[29] 
Vellodi A. Lysosomal storage disorders. Br J Haematol  2005; 128(4): 413-31.
[http://dx.doi.org/10.1111/j.1365-2141.2004.05293.x] [PMID:  15686451] 
[30] 
Segatori L.  Impairment of homeostasis in lysosomal storage disorders. 2014; 66: 472-7.
[http://dx.doi.org/10.1002/iub.1288] 
[31] 
de Pablo-Latorre R, Saide A, Polishhuck EV, Nusco E, Fraldi A, Ballabio A. Impaired parkin-mediated mitochondrial targeting to autophagosomes differentially contributes to tissue pathology in lysosomal storage diseases. Hum Mol Genet  2012; 21(8): 1770-81.
[http://dx.doi.org/10.1093/hmg/ddr610] [PMID:  22215441] 
[32] 
Parkinson-Lawrence EJ, Shandala T, Prodoehl M, Plew R, Borlace GN, Brooks DA. Lysosomal storage disease: Revealing lysosomal function and physiology. Physiology (Bethesda)  2010; 25(2): 102-15.
[http://dx.doi.org/10.1152/physiol.00041.2009] [PMID:  20430954] 
[33] 
Alroy J, Garganta C, Wiederschain G. Secondary biochemical and morphological consequences in lysosomal storage diseases. Biochem Biokhim  2014; 79(7): 619-36.
[http://dx.doi.org/10.1134/S0006297914070049] 
[34] 
Sardiello M, Palmieri M, di Ronza A, et al. A gene network regulating lysosomal biogenesis and function. Science  2009; 325(5939): 473-7.
[http://dx.doi.org/10.1126/science.1174447] [PMID:  19556463] 
[35] 
Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell  2010; 141(2): 290-303.
[http://dx.doi.org/10.1016/j.cell.2010.02.024] [PMID:  20381137] 
[36] 
Samie MA, Xu H. Lysosomal exocytosis and lipid storage disorders. J Lipid Res  2014; 55(6): 995-1009.
[http://dx.doi.org/10.1194/jlr.R046896] [PMID:  24668941] 
[37] 
Ballabio A, Gieselmann V. Lysosomal disorders: From storage to cellular damage. Biochim Biophys Acta  2009; 1793(4): 684-96.
[http://dx.doi.org/10.1016/j.bbamcr.2008.12.001] [PMID:  19111581] 
[38] 
Germain DP. Gaucher’s disease: A paradigm for interventional genetics. Clin Genet  2004; 65(2): 77-86.
[http://dx.doi.org/10.1111/j.0009-9163.2004.00217.x] [PMID:  14984463] 
[39] 
Stirnemann J, Belmatoug N, Camou F, et al. A review of Gaucher disease pathophysiology, clinical presentation and treatments. Int J Mol Sci  2017; 18(2)E441
[http://dx.doi.org/10.3390/ijms18020441] [PMID:  28218669] 
[40] 
Ishii S. Pharmacological chaperone therapy for Fabry disease. Proc Jpn Acad, Ser B, Phys Biol Sci  2012; 88(1): 18-30.
[http://dx.doi.org/10.2183/pjab.88.18] [PMID:  22241068] 
[41] 
Brady RO. Enzymatic abnormalities in diseases of sphingolipid metabolism. Clin Chem  1967; 13(7): 565-77.
[PMID:  5006481] 
[42] 
Schuchman EH, Wasserstein MP. Types A and B Niemann-Pick Disease. Pediatr Endocrinol Rev  2016; 13(Suppl. 1): 674-81.
[PMID:  27491215] 
[43] 
Lusa S, Blom TS, Eskelinen EL, et al. Depletion of rafts in late endocytic membranes is controlled by NPC1-dependent recycling of cholesterol to the plasma membrane. J Cell Sci  2001; 114(Pt 10): 1893-900.
[PMID:  11329376] 
[44] 
Vitner EB, Platt FM, Futerman AH. Common and uncommon pathogenic cascades in lysosomal storage diseases. J Biol Chem  2010; 285(27): 20423-7.
[http://dx.doi.org/10.1074/jbc.R110.134452] [PMID:  20430897] 
[45] 
Rosenberg JB, Kaminsky SM, Aubourg P, Crystal RG, Sondhi D. Gene therapy for metachromatic leukodystrophy. J Neurosci Res  2016; 94(11): 1169-79.
[http://dx.doi.org/10.1002/jnr.23792] [PMID:  27638601] 
[46] 
Hadi M, Swinburn P, Nalysnyk L, Hamed A, Mehta A. A health state utility valuation study to assess the impact of treatment mode of administration in Gaucher disease. Orphanet J Rare Dis  2018; 13(1): 159.
[http://dx.doi.org/10.1186/s13023-018-0903-6] [PMID:  30201003] 
[47] 
Abdel Razek AA, Abd El-Gaber N, Abdalla A, Fathy A, Azab A, Rahman AA. Apparent diffusion coefficient vale of the brain in patients with Gaucher’s disease type II and type III. Neuroradiology  2009; 51(11): 773-9.
[http://dx.doi.org/10.1007/s00234-009-0548-1] [PMID:  19603156] 
[48] 
Schuchman EH, Desnick RJ. Types A and B Niemann-Pick disease. Mol Genet Metab  2017; 120(1-2): 27-33.
[49] 
Broekman ML, Tierney LA, Benn C, Chawla P, Cha JH, Sena-Esteves M. Mechanisms of distribution of mouse beta-galactosidase in the adult GM1-gangliosidosis brain. Gene Ther  2009; 16(2): 303-8.
[http://dx.doi.org/10.1038/gt.2008.149] [PMID:  18818671] 
[50] 
Suzuki K, Yamaguchi A, Yamanaka S, et al. Accumulated α-synuclein affects the progression of GM2 gangliosidoses  Exp Neurol 2016; 284(Pt A): 38-49.
[http://dx.doi.org/10.1016/j.expneurol.2016.07.011] [PMID: 27453479] 
[51] 
Kitakaze K, Tasaki C, Tajima Y, et al. Combined replacement effects of human modified β-hexosaminidase B and GM2 activator protein on GM2 gangliosidoses fibroblasts. Biochem Biophys Rep  2016; 7: 157-63.
[http://dx.doi.org/10.1016/j.bbrep.2016.04.012] [PMID:  28955902] 
[52] 
Seyrantepe V, Demir SA, Timur ZK, et al. Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease  Exp Neurol 2018; 299(Pt A): 26-41.
[http://dx.doi.org/10.1016/j.expneurol.2017.09.012] [PMID: 28974375] 
[53] 
van Rappard DF, Boelens JJ, Wolf NI. Metachromatic leukodystrophy: Disease spectrum and approaches for treatment. Best Pract Res Clin Endocrinol Metab  2015; 29(2): 261-73.
[http://dx.doi.org/10.1016/j.beem.2014.10.001] [PMID:  25987178] 
[54] 
Mühlstein A, Gelperina S, Shipulo E, Maksimenko O, Kreuter J. Arylsulfatase A bound to poly(butyl cyanoacrylate) nanoparticles for enzyme replacement therapy--physicochemical evaluation. Pharmazie  2014; 69(7): 518-24.
[PMID:  25073397] 
[55] 
Zampetti A, Fania L, Antuzzi D, et al. Mutation identification of Fabry disease in families with other lysosomal storage disorders. Clin Genet  2013; 84(3): 281-5.
[http://dx.doi.org/10.1111/cge.12071] [PMID:  23210910] 
[56] 
Gilkes JA, Heldermon CD. Mucopolysaccharidosis III (Sanfilippo Syndrome)- disease presentation and experimental therapies. Pediatr Endocrinol Rev  2014; 12(Suppl. 1): 133-40.
[PMID:  25345095] 
[57] 
Andrade F, Aldámiz-Echevarría L, Llarena M, Couce ML. Sanfilippo syndrome: Overall review. Pediatr Int  2015; 57(3): 331-8.
[http://dx.doi.org/10.1111/ped.12636] [PMID:  25851924] 
[58] 
Davison JE, Kearney S, Horton J, Foster K, Peet AC, Hendriksz CJ. Intellectual and neurological functioning in Morquio syndrome (MPS IVa). J Inherit Metab Dis  2013; 36(2): 323-8.
[http://dx.doi.org/10.1007/s10545-011-9430-5] [PMID:  22231379] 
[59] 
Ohto U, Usui K, Ochi T, Yuki K, Satow Y, Shimizu T. Crystal structure of human β-galactosidase: Structural basis of Gm1 gangliosidosis and morquio B diseases. J Biol Chem  2012; 287(3): 1801-12.
[http://dx.doi.org/10.1074/jbc.M111.293795] [PMID:  22128166] 
[60] 
Behfar M, Dehghani SS, Rostami T, Ghavamzadeh A, Hamidieh AA. Non-sibling hematopoietic stem cell transplantation using myeloablative conditioning regimen in children with Maroteaux-Lamy syndrome: A brief report. Pediatr Transplant  2017; 21(5): 21.
[http://dx.doi.org/10.1111/petr.12981] [PMID:  28707754] 
[61] 
Montaño AM, Lock-Hock N, Steiner RD, et al. Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet  2016; 53(6): 403-18.
[http://dx.doi.org/10.1136/jmedgenet-2015-103322] [PMID:  26908836] 
[62] 
Reichert R, Campos LG, Vairo F, et al. Neuroimaging Findings in Patients with Mucopolysaccharidosis: What You Really Need to Know. Radiographics  2016; 36(5): 1448-62.
[http://dx.doi.org/10.1148/rg.2016150168] [PMID:  27618324] 
[63] 
Lim JA, Kakhlon O, Li L, Myerowitz R, Raben N. Pompe disease: Shared and unshared features of lysosomal storage disorders. Rare Dis  2015; 3(1)e1068978
[http://dx.doi.org/10.1080/21675511.2015.1068978] [PMID:  26619007] 
[64] 
Borgwardt L, Lund AM, Dali CI. Alpha-mannosidosis - a review of genetic, clinical findings and options of treatment. Pediatr Endocrinol Rev  2014; 12(Suppl. 1): 185-91.
[PMID:  25345101] 
[65] 
Huynh T, Khan JM, Ranganathan S. A comparative structural bioinformatics analysis of inherited mutations in β-D-Mannosidase across multiple species reveals a genotype-phenotype correlation. BMC Genomics  2011; 12(Suppl. 3): S22.
[http://dx.doi.org/10.1186/1471-2164-12-S3-S22] [PMID:  22369051] 
[66] 
Malatt C, Koning JL, Naheedy J. Skeletal and Brain Abnormalities in Fucosidosis, a Rare Lysosomal Storage Disorder. J Radiol Case Rep  2015; 9(5): 30-8.
[http://dx.doi.org/10.3941/jrcr.v9i5.2149] [PMID:  26622931] 
[67] 
Banning A, Gülec C, Rouvinen J, Gray SJ, Tikkanen R. Identification of Small Molecule Compounds for Pharmacological Chaperone Therapy of Aspartylglucosaminuria. Sci Rep  2016; 6: 37583.
[http://dx.doi.org/10.1038/srep37583] [PMID:  27876883] 
[68] 
Albracht SPJ, Allon E, van Pelt J. Multiple exo-glycosidases in human serum as detected with the substrate DNP-α-GalNAc. I. A new assay for lysosomal α-N-acetylgalactosaminidase. BBA Clin  2017; 8: 84-9.
[http://dx.doi.org/10.1016/j.bbacli.2017.10.001] [PMID:  29062717] 
[69] 
Khan A, Sergi C. Sialidosis: A Review of Morphology and Molecular Biology of a Rare Pediatric Disorder. Diagnostics (Basel)  2018; 8(2)E29
[http://dx.doi.org/10.3390/diagnostics8020029] [PMID:  29693572] 
[70] 
Tüysüz B, Kasapçopur Ö, Alkaya DU, Şahin S, Sözeri B, Yeşil G. Mucolipidosis type III gamma: Three novel mutation and genotype-phenotype study in eleven patients. Gene  2018; 642: 398-407.
[http://dx.doi.org/10.1016/j.gene.2017.11.052] [PMID:  29170090] 
[71] 
Kostadinov S, Shah BA, Alroy J, Phornphutkul C. A case of galactosialidosis with novel mutations of the protective protein/cathepsin a gene: Diagnosis prompted by trophoblast vacuolization on placental examination. Pediatr Dev Pathol  2014; 17(6): 474-7.
[http://dx.doi.org/10.2350/14-05-1500-CR.1] [PMID:  25075748] 
[72] 
Markmann SJ, Christie-Reid J, Rosenberg JB, et al. Attenuation of the Niemann-Pick type C2 disease phenotype by intracisternal administration of an AAVrh.10 vector expressing Npc2. Exp Neurol  2018; 306: 22-33.
[http://dx.doi.org/10.1016/j.expneurol.2018.04.001] [PMID:  29655638] 
[73] 
Dierks T, Schlotawa L, Frese MA, Radhakrishnan K, von Figura K, Schmidt B. Molecular basis of multiple sulfatase deficiency, mucolipidosis II/III and Niemann-Pick C1 disease - Lysosomal storage disorders caused by defects of non-lysosomal proteins. Biochim Biophys Acta  2009; 1793(4): 710-25.
[http://dx.doi.org/10.1016/j.bbamcr.2008.11.015] [PMID:  19124046] 
[74] 
Hossain MA, Higaki K, Shinpo M, et al. Chemical chaperone treatment for galactosialidosis: Effect of NOEV on β-galactosidase activities in fibroblasts. Brain Dev  2016; 38(2): 175-80.
[http://dx.doi.org/10.1016/j.braindev.2015.07.006] [PMID:  26259553] 
[75] 
Hawkins-Salsbury JA, Cooper JD, Sands MS. Pathogenesis and therapies for infantile neuronal ceroid lipofuscinosis (infantile CLN1 disease). Biochim Biophys Acta  2013; 1832(11): 1906-9.
[http://dx.doi.org/10.1016/j.bbadis.2013.05.026] [PMID:  23747979] 
[76] 
Fietz M, AlSayed M, Burke D, et al. Diagnosis of neuronal ceroid lipofuscinosis type 2 (CLN2 disease): Expert recommendations for early detection and laboratory diagnosis. Mol Genet Metab  2016; 119(1-2): 160-7.
[http://dx.doi.org/10.1016/j.ymgme.2016.07.011] [PMID:  27553878] 
[77] 
Chandrachud U, Walker MW, Simas AM, et al. Unbiased Cell-based Screening in a Neuronal Cell Model of Batten Disease Highlights an Interaction between Ca2+ Homeostasis, Autophagy, and CLN3 Protein Function. J Biol Chem  2015; 290(23): 14361-80.
[http://dx.doi.org/10.1074/jbc.M114.621706] [PMID:  25878248] 
[78] 
Benitez BA, Alvarado D, Cai Y, et al. Exome-sequencing confirms DNAJC5 mutations as cause of adult neuronal ceroid-lipofuscinosis. PLoS One  2011; 6(11)e26741
[http://dx.doi.org/10.1371/journal.pone.0026741] [PMID:  22073189] 
[79] 
Larkin H, Ribeiro MG, Lavoie C. Topology and membrane anchoring of the lysosomal storage disease-related protein CLN5. Hum Mutat  2013; 34(12): 1688-97.
[http://dx.doi.org/10.1002/humu.22443] [PMID:  24038957] 
[80] 
Kurze AK, Galliciotti G, Heine C, Mole SE, Quitsch A, Braulke T. Pathogenic mutations cause rapid degradation of lysosomal storage disease-related membrane protein CLN6. Hum Mutat  2010; 31(2): E1163-74.
[http://dx.doi.org/10.1002/humu.21184] [PMID:  20020536] 
[81] 
Brandenstein L, Schweizer M, Sedlacik J, Fiehler J, Storch S. Lysosomal dysfunction and impaired autophagy in a novel mouse model deficient for the lysosomal membrane protein Cln7. Hum Mol Genet  2016; 25(4): 777-91.
[http://dx.doi.org/10.1093/hmg/ddv615] [PMID:  26681805] 
[82] 
Lingaas F, Guttersrud OA, Arnet E, Espenes A. Neuronal ceroid lipofuscinosis in Salukis is caused by a single base pair insertion in CLN8. Anim Genet  2018; 49(1): 52-8.
[http://dx.doi.org/10.1111/age.12629] [PMID:  29446145] 
[83] 
Smith KR, Damiano J, Franceschetti S, et al. Strikingly different clinicopathological phenotypes determined by progranulin-mutation dosage. Am J Hum Genet  2012; 90(6): 1102-7.
[http://dx.doi.org/10.1016/j.ajhg.2012.04.021] [PMID:  22608501] 
[84] 
Peters J, Rittger A, Weisner R, et al. Lysosomal integral membrane protein type-2 (LIMP-2/SCARB2) is a substrate of cathepsin-F, a cysteine protease mutated in type-B-Kufs-disease. Biochem Biophys Res Commun  2015; 457(3): 334-40.
[http://dx.doi.org/10.1016/j.bbrc.2014.12.111] [PMID:  25576872] 
[85] 
Staropoli JF, Karaa A, Lim ET, et al. A homozygous mutation in KCTD7 links neuronal ceroid lipofuscinosis to the ubiquitin-proteasome system. Am J Hum Genet  2012; 91(1): 202-8.
[http://dx.doi.org/10.1016/j.ajhg.2012.05.023] [PMID:  22748208] 
[86] 
Yardeni M, Weisman O, Mandel H, et al. Psychiatric and cognitive characteristics of individuals with Danon disease (LAMP2 gene mutation). Am J Med Genet A  2017; 173(9): 2461-6.
[http://dx.doi.org/10.1002/ajmg.a.38320] [PMID:  28627787] 
[87] 
Couce ML, Macías-Vidal J, Castiñeiras DE, et al. The early detection of Salla disease through second-tier tests in newborn screening: How to face incidental findings. Eur J Med Genet  2014; 57(9): 527-31.
[http://dx.doi.org/10.1016/j.ejmg.2014.06.005] [PMID:  24993898] 
[88] 
Vanier MT. Niemann-Pick diseases. Handb Clin Neurol  2013; 113: 1717-21.
[http://dx.doi.org/10.1016/B978-0-444-59565-2.00041-1] [PMID:  23622394] 
[89] 
Wakabayashi K, Gustafson AM, Sidransky E, Goldin E. Mucolipidosis type IV: An update. Mol Genet Metab  2011; 104(3): 206-13.
[http://dx.doi.org/10.1016/j.ymgme.2011.06.006] [PMID:  21763169] 
[90] 
Lozano ML, Rivera J, Sánchez-Guiu I, Vicente V. Towards the targeted management of Chediak-Higashi syndrome. Orphanet J Rare Dis  2014; 9: 132.
[http://dx.doi.org/10.1186/s13023-014-0132-6] [PMID:  25129365] 
[91] 
Saftig PK. Lysosome biogenesis and lysosomal membrane proteins: Trafficking meets function.  J Nat Rev Mol Cell Biol Chem 2009; pp. 623-35.
[92] 
El-Chemaly S, Young LR. Hermansky-Pudlak Syndrome. Clin Chest Med  2016; 37(3): 505-11.
[http://dx.doi.org/10.1016/j.ccm.2016.04.012] [PMID:  27514596] 
[93] 
Muro S. New biotechnological and nanomedicine strategies for treatment of lysosomal storage disorders. Wiley Interdiscip Rev Nanomed Nanobiotechnol  2010; 2(2): 189-204.
[http://dx.doi.org/10.1002/wnan.73] [PMID:  20112244] 
[94] 
Cox TM, Cachón-González MB. The cellular pathology of lysosomal diseases. J Pathol  2012; 226(2): 241-54.
[http://dx.doi.org/10.1002/path.3021] [PMID:  21990005] 
[95] 
Rama Rao KV, Kielian T. Astrocytes and lysosomal storage diseases. Neuroscience  2016; 323: 195-206.
[http://dx.doi.org/10.1016/j.neuroscience.2015.05.061] [PMID:  26037807] 
[96] 
Shachar T, Lo Bianco C, Recchia A, Wiessner C, Raas-Rothschild A, Futerman AH. Lysosomal storage disorders and Parkinson’s disease: Gaucher disease and beyond. Mov Disord  2011; 26(9): 1593-604.
[http://dx.doi.org/10.1002/mds.23774] [PMID:  21618611] 
[97] 
Dehay B, Martinez-Vicente M, Caldwell GA, et al. Lysosomal impairment in Parkinson’s disease. Mov Disord  2013; 28(6): 725-32.
[http://dx.doi.org/10.1002/mds.25462] [PMID:  23580333] 
[98] 
Goo MS, Sancho L, Slepak N, et al. Activity-dependent trafficking of lysosomes in dendrites and dendritic spines. J Cell Biol  2017; 216(8): 2499-513.
[http://dx.doi.org/10.1083/jcb.201704068] [PMID:  28630145] 
[99] 
McKenna MC, Schuck PF, Ferreira GC. Fundamentals of CNS energy metabolism and alterations in lysosomal storage diseases. J Neurochem  2019; 148(5): 590-9.
[PMID:  30144055] 
[100] 
Annunziata I, Sano R, d’Azzo A. Mitochondria-associated ER membranes (MAMs) and lysosomal storage diseases. Cell Death Dis  2018; 9(3): 328.
[http://dx.doi.org/10.1038/s41419-017-0025-4] [PMID:  29491402] 
[101] 
Wong YC, Ysselstein D, Krainc D. Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature  2018; 554(7692): 382-6.
[http://dx.doi.org/10.1038/nature25486] [PMID:  29364868] 
[102] 
Schousboe A, Scafidi S, Bak LK, Waagepetersen HS, McKenna MC. Glutamate metabolism in the brain focusing on astrocytes. Adv Neurobiol  2014; 11: 13-30.
[http://dx.doi.org/10.1007/978-3-319-08894-5_2] [PMID:  25236722] 
[103] 
Sidoryk-Wegrzynowicz M, Lee E, Aschner M. Mechanism of Mn(II)-mediated dysregulation of glutamine-glutamate cycle: Focus on glutamate turnover. J Neurochem  2012; 122(4): 856-67.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07835.x] [PMID:  22708868] 
[104] 
De Duve C. The lysosome. Sci Am  1963; 208: 64-72.
[http://dx.doi.org/10.1038/scientificamerican0563-64] [PMID:  14025755] 
[105] 
Brady RO, Kanfer JN, Shapiro D. Metabolism of Glucocerebrosides. II. Evidence of an enzymatic deficiency in Gaucher’s diseases. Biochem Biophys Res Commun  1965; 18: 221-5.
[http://dx.doi.org/10.1016/0006-291X(65)90743-6] [PMID:  14282020] 
[106] 
Barton NW, Brady RO, Dambrosia JM, et al. Replacement therapy for inherited enzyme deficiency--macrophage-targeted glucocerebrosidase for Gaucher’s disease. N Engl J Med  1991; 324(21): 1464-70.
[http://dx.doi.org/10.1056/NEJM199105233242104] [PMID:  2023606] 
[107] 
Oh DB. Glyco-engineering strategies for the development of therapeutic enzymes with improved efficacy for the treatment of lysosomal storage diseases. BMB Rep  2015; 48(8): 438-44.
[http://dx.doi.org/10.5483/BMBRep.2015.48.8.101] [PMID:  25999178] 
[108] 
Schiffmann R, Kopp JB, Austin HA III, et al. Enzyme replacement therapy in Fabry disease: A randomized controlled trial. JAMA  2001; 285(21): 2743-9.
[http://dx.doi.org/10.1001/jama.285.21.2743] [PMID:  11386930] 
[109] 
Van den Hout H, Reuser AJ, Vulto AG, Loonen MC, Cromme-Dijkhuis A, Van der Ploeg AT. Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet  2000; 356(9227): 397-8.
[http://dx.doi.org/10.1016/S0140-6736(00)02533-2] [PMID:  10972374] 
[110] 
Ohashi T. Enzyme replacement therapy for lysosomal storage diseases. Pediatr Endocrinol Rev  2012; 10(Suppl. 1): 26-34.
[PMID:  23330243] 
[111] 
Kakkis ED, Muenzer J, Tiller GE, et al. Enzyme-replacement therapy in mucopolysaccharidosis I. N Engl J Med  2001; 344(3): 182-8.
[http://dx.doi.org/10.1056/NEJM200101183440304] [PMID:  11172140] 
[112] 
Harmatz P, Giugliani R, Schwartz I, et al. Enzyme replacement therapy for mucopolysaccharidosis VI: A phase 3, randomized, double-blind, placebo-controlled, multinational study of recombinant human N-acetylgalactosamine 4-sulfatase (recombinant human arylsulfatase B or rhASB) and follow-on, open-label extension study. J Pediatr  2006; 148(4): 533-9.
[http://dx.doi.org/10.1016/j.jpeds.2005.12.014] [PMID:  16647419] 
[113] 
Espejo-Mojica AJ, Alméciga-Díaz CJ, Rodríguez A, et al. Human recombinant lysosomal enzymes produced in microorganisms. Mol Genet Metab  2015; 116(1-2): 13-23.
[http://dx.doi.org/10.1016/j.ymgme.2015.06.001] [PMID:  26071627] 
[114] 
Scarpa M, Bellettato CM, Lampe C, Begley DJ. Neuronopathic lysosomal storage disorders: Approaches to treat the central nervous system. Best Pract Res Clin Endocrinol Metab  2015; 29(2): 159-71.
[http://dx.doi.org/10.1016/j.beem.2014.12.001] [PMID:  25987170] 
[115] 
Mu TW, Fowler DM, Kelly JW. Partial restoration of mutant enzyme homeostasis in three distinct lysosomal storage disease cell lines by altering calcium homeostasis. PLoS Biol  2008; 6(2)e26
[http://dx.doi.org/10.1371/journal.pbio.0060026] [PMID:  18254660] 
[116] 
McGovern MM, Wasserstein MP, Kirmse B, et al. Novel first-dose adverse drug reactions during a phase I trial of olipudase alfa (recombinant human acid sphingomyelinase) in adults with Niemann-Pick disease type B (acid sphingomyelinase deficiency). Genet Med  2016; 18(1): 34-40.
[http://dx.doi.org/10.1038/gim.2015.24] [PMID:  25834946] 
[117] 
Ultragenyx, Pharmaceutical, Inc. A Long-Term Open-Label Treatment and Extension Study of UX003 rhGUS Enzyme Replacement Therapy in Subjects With MPS 7. www.clinicaltrils.gov2019.
[118] 
Solomon M, Muro S. Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives. Adv Drug Deliv Rev  2017; 118: 109-34.
[http://dx.doi.org/10.1016/j.addr.2017.05.004] [PMID:  28502768] 
[119] 
Begley DJ, Pontikis CC, Scarpa M. Lysosomal storage diseases and the blood-brain barrier. Curr Pharm Des  2008; 14(16): 1566-80.
[http://dx.doi.org/10.2174/138161208784705504] [PMID:  18673198] 
[120] 
Pardridge WM. Delivery of Biologics Across the Blood-Brain Barrier with Molecular Trojan Horse Technology. BioDrugs  2017; 31(6): 503-19.
[http://dx.doi.org/10.1007/s40259-017-0248-z] [PMID:  29067674] 
[121] 
Lachmann RH. Enzyme replacement therapy for lysosomal storage diseases. Curr Opin Pediatr  2011; 23(6): 588-93.
[http://dx.doi.org/10.1097/MOP.0b013e32834c20d9] [PMID:  21946346] 
[122] 
de Filippis L. Neural stem cell-mediated therapy for rare brain diseases: Perspectives in the near future for LSDs and MNDs. Histol Histopathol  2011; 26(8): 1093-109.
[PMID:  21692041] 
[123] 
Siddiqi F, Wolfe JH. Stem Cell Therapy for the Central Nervous System in Lysosomal Storage Diseases. Hum Gene Ther  2016; 27(10): 749-57.
[http://dx.doi.org/10.1089/hum.2016.088] [PMID:  27420186] 
[124] 
Lund TC. Hematopoietic stem cell transplant for lysosomal storage diseases. Pediatr Endocrinol Rev  2013; 11(Suppl. 1): 91-8.
[PMID:  24380127] 
[125] 
Tamaki SJ, Jacobs Y, Dohse M, et al. Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis. Cell Stem Cell  2009; 5(3): 310-9.
[http://dx.doi.org/10.1016/j.stem.2009.05.022] [PMID:  19733542] 
[126] 
Ricca A, Rufo N, Ungari S, et al. Combined gene/cell therapies provide long-term and pervasive rescue of multiple pathological symptoms in a murine model of globoid cell leukodystrophy. Hum Mol Genet  2015; 24(12): 3372-89.
[http://dx.doi.org/10.1093/hmg/ddv086] [PMID:  25749991] 
[127] 
Shihabuddin LS, Numan S, Huff MR, et al. Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology. J Neurosci  2004; 24(47): 10642-51.
[http://dx.doi.org/10.1523/JNEUROSCI.3584-04.2004] [PMID:  15564580] 
[128] 
Kawabata K, Migita M, Mochizuki H, et al. Ex vivo cell-mediated gene therapy for metachromatic leukodystrophy using neurospheres. Brain Res  2006; 1094(1): 13-23.
[http://dx.doi.org/10.1016/j.brainres.2006.03.116] [PMID:  16729983] 
[129] 
Arthur JR, Lee JP, Snyder EY, Seyfried TN. Therapeutic effects of stem cells and substrate reduction in juvenile Sandhoff mice. Neurochem Res  2012; 37(6): 1335-43.
[http://dx.doi.org/10.1007/s11064-012-0718-0] [PMID:  22367451] 
[130] 
Robinson AJ, Zhao G, Rathjen J, et al. Embryonic stem cell-derived glial precursors as a vehicle for sulfamidase production in the MPS-IIIA mouse brain. Cell Transplant  2010; 19(8): 985-98.
[http://dx.doi.org/10.3727/096368910X498944] [PMID:  20350350] 
[131] 
Fukuhara Y, Li X-K, Kitazawa Y, et al. Histopathological and behavioral improvement of murine mucopolysaccharidosis type VII by intracerebral transplantation of neural stem cells. Mol Ther  2006; 13(3): 548-55.
[http://dx.doi.org/10.1016/j.ymthe.2005.09.020] [PMID:  16316785] 
[132] 
Shihabuddin L, Numan S, Stewart G. Cell therapy for neurome-tabolic disorders 2005.
[133] 
Spratley SJ, Deane JE. New therapeutic approaches for Krabbe disease: The potential of pharmacological chaperones. J Neurosci Res  2016; 94(11): 1203-19.
[http://dx.doi.org/10.1002/jnr.23762] [PMID:  27638604] 
[134] 
Arakawa T, Ejima D, Kita Y, Tsumoto K. Small molecule pharmacological chaperones: From thermodynamic stabilization to pharmaceutical drugs. Biochim Biophys Acta  2006; 1764(11): 1677-87.
[http://dx.doi.org/10.1016/j.bbapap.2006.08.012] [PMID:  17046342] 
[135] 
Hill CH, Viuff AH, Spratley SJ, et al. Azasugar inhibitors as pharmacological chaperones for Krabbe disease. Chem Sci (Camb)  2015; 6(5): 3075-86.
[http://dx.doi.org/10.1039/C5SC00754B] [PMID:  26029356] 
[136] 
Kirkegaard T, Roth AG, Petersen NH, et al. Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature  2010; 463(7280): 549-53.
[http://dx.doi.org/10.1038/nature08710] [PMID:  20111001] 
[137] 
Parenti G, Moracci M, Fecarotta S, Andria G. Pharmacological chaperone therapy for lysosomal storage diseases. Future Med Chem  2014; 6(9): 1031-45.
[http://dx.doi.org/10.4155/fmc.14.40] [PMID:  25068986] 
[138] 
Parenti G, Andria G, Valenzano KJ. Pharmacological Chaperone Therapy: Preclinical Development, Clinical Translation, and Prospects for the Treatment of Lysosomal Storage Disorders. Mol Ther  2015; 23(7): 1138-48.
[http://dx.doi.org/10.1038/mt.2015.62] [PMID:  25881001] 
[139] 
Parenti G, Fecarotta S, la Marca G, et al. A chaperone enhances blood α-glucosidase activity in Pompe disease patients treated with enzyme replacement therapy. Mol Ther  2014; 22(11): 2004-12.
[http://dx.doi.org/10.1038/mt.2014.138] [PMID:  25052852] 
[140] 
Kelly JM, Bradbury A, Martin DR, Byrne ME. Emerging therapies for neuropathic lysosomal storage disorders. Prog Neurobiol  2017; 152: 166-80.
[http://dx.doi.org/10.1016/j.pneurobio.2016.10.002] [PMID:  27725193] 
[141] 
Sands MS, Davidson BL. Gene therapy for lysosomal storage diseases. Mol Ther  2006; 13(5): 839-49.
[http://dx.doi.org/10.1016/j.ymthe.2006.01.006] [PMID:  16545619] 
[142] 
Daya S, Berns KI. Gene therapy using adeno-associated virus vectors. Clin Microbiol Rev  2008; 21(4): 583-93.
[http://dx.doi.org/10.1128/CMR.00008-08] [PMID:  18854481] 
[143] 
Biffi A, Montini E, Lorioli L, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science  2013; 341(6148)1233158
[http://dx.doi.org/10.1126/science.1233158] [PMID:  23845948] 
[144] 
Gray-Edwards HL, Randle AN, Maitland SA, et al. Adeno-associated virus gene therapy in a sheep model of Tay-Sachs disease. Hum Gene Ther  2018; 29(3): 312-26.
[http://dx.doi.org/10.1089/hum.2017.163] [PMID:  28922945] 
[145] 
Solovyeva V, Shaimardanova A, Chulpanova D, et al. New Approaches to Tay-Sachs Disease Therapy. Front Physiol  2018; 9: 1663.
[http://dx.doi.org/10.3389/fphys.2018.01663] 
[146] 
Sena-Esteves M, Cox TM, Cachon-gozalez MB, et al.  Methods for the treatment of Tay-Sachs disease, Sandhoff disease and GM1- gangliosidosis. WO2012145646A1 2013.
[147] 
McIntyre C, Byers S, Anson DS. Correction of mucopolysaccharidosis type IIIA somatic and central nervous system pathology by lentiviral-mediated gene transfer. J Gene Med  2010; 12(9): 717-28.
[http://dx.doi.org/10.1002/jgm.1489] [PMID:  20683858] 
[148] 
Worgall S, Sondhi D, Hackett NR, et al. Treatment of late infantile neuronal ceroid lipofuscinosis by CNS administration of a serotype 2 adeno-associated virus expressing CLN2 cDNA. Hum Gene Ther  2008; 19(5): 463-74.
[http://dx.doi.org/10.1089/hum.2008.022] [PMID:  18473686] 
[149] 
Passini MA, Stewart GR. Gene therapy for neurometabolic disorders 2005.
[150] 
Rastall DP, Amalfitano A. Recent advances in gene therapy for lysosomal storage disorders. Appl Clin Genet  2015; 8: 157-69.
[PMID:  26170711] 
[151] 
Raben N, Schreiner C, Baum R, et al. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder--murine Pompe disease. Autophagy  2010; 6(8): 1078-89.
[http://dx.doi.org/10.4161/auto.6.8.13378] [PMID:  20861693] 
[152] 
Spampanato C, Feeney E, Li L, et al. Transcription factor EB (TFEB) is a new therapeutic target for Pompe disease. EMBO Mol Med  2013; 5(5): 691-706.
[http://dx.doi.org/10.1002/emmm.201202176] [PMID:  23606558] 
[153] 
Auclair D, Finnie J, Walkley SU, et al. Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats. Pediatr Res  2012; 71(1): 39-45.
[http://dx.doi.org/10.1038/pr.2011.13] [PMID:  22289849] 
[154] 
Onaca-Fischer O, Liu J, Inglin M, Palivan CG. Polymeric nanocarriers and nanoreactors: A survey of possible therapeutic applications. Curr Pharm Des  2012; 18(18): 2622-43.
[http://dx.doi.org/10.2174/138161212800492822] [PMID:  22512447] 
[155] 
Pirooznia N, Hasannia S, Lotfi AS, et al. Encapsulation of Alpha-1 antitrypsin in PLGA nanoparticles: In Vitro characterization as an effective aerosol formulation in pulmonary diseases. J Nanobiotechnology  2012; 20.
[156] 
Dziubla TD, Karim A, Muzykantov VR. Polymer nanocarriers protecting active enzyme cargo against proteolysis. J Control Release  2005; 102(2): 427-39.
[http://dx.doi.org/10.1016/j.jconrel.2004.10.017] [PMID:  15653162] 
[157] 
Böckenhoff A, Cramer S, Wölte P, et al. Comparison of five peptide vectors for improved brain delivery of the lysosomal enzyme arylsulfatase A. J Neurosci  2014; 34(9): 3122-9.
[http://dx.doi.org/10.1523/JNEUROSCI.4785-13.2014] [PMID:  24573272] 
[158] 
Schuster T, Mühlstein A, Yaghootfam C, et al. Potential of surfactant-coated nanoparticles to improve brain delivery of arylsulfatase A. J Control Release  2017; 253: 1-10.
[http://dx.doi.org/10.1016/j.jconrel.2017.02.016] [PMID:  28215668] 
[159] 
Maga JA, Zhou J, Kambampati R, et al. Glycosylation-independent lysosomal targeting of acid α-glucosidase enhances muscle glycogen clearance in pompe mice. J Biol Chem  2013; 288(3): 1428-38.
[http://dx.doi.org/10.1074/jbc.M112.438663] [PMID:  23188827] 
[160] 
Montaño AM, Oikawa H, Tomatsu S, et al. Acidic amino acid tag enhances response to enzyme replacement in mucopolysaccharidosis type VII mice. Mol Genet Metab  2008; 94(2): 178-89.
[http://dx.doi.org/10.1016/j.ymgme.2008.01.007] [PMID:  18359257] 
[161] 
Zhou QH, Boado RJ, Lu JZ, Hui EK, Pardridge WM. Brain-penetrating IgG-iduronate 2-sulfatase fusion protein for the mouse. Drug Metab Dispos  2012; 40(2): 329-35.
[http://dx.doi.org/10.1124/dmd.111.042903] [PMID:  22065691] 
[162] 
Sands MS. Mucopolysaccharidosis type VII: A powerful experimental system and therapeutic challenge. Pediatr Endocrinol Rev  2014; 12(Suppl. 1): 159-65.
[PMID:  25345098] 
[163] 
Liu G, Martins I, Wemmie JA, Chiorini JA, Davidson BL. Functional correction of CNS phenotypes in a lysosomal storage disease model using adeno-associated virus type 4 vectors. J Neurosci  2005; 25(41): 9321-7.
[http://dx.doi.org/10.1523/JNEUROSCI.2936-05.2005] [PMID:  16221840] 
[164] 
Hsu J, Bhowmick T, Burks SR, Kao JP, Muro S. Enhancing biodistribution of therapeutic enzymes in vivo by modulating surface coating and concentration of ICAM-1-targeted nanocarriers. J Biomed Nanotechnol  2014; 10(2): 345-54.
[http://dx.doi.org/10.1166/jbn.2014.1718] [PMID:  24738342] 
[165] 
Yu X, Trase I, Ren M, et al. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery. J Nanomater  2016; 20161087250
[166] 
Leach JC, Wang A, Ye K, Jin S. A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery. Int J Mol Sci  2016; 17(3): 380.
[http://dx.doi.org/10.3390/ijms17030380] [PMID:  26985893] 
[167] 
Silva LM, Hill LE, Figueiredo E, Gomes CL. Delivery of phytochemicals of tropical fruit by-products using poly (DL-lactide-co-glycolide) (PLGA) nanoparticles: Synthesis, characterization, and antimicrobial activity. Food Chem  2014; 165: 362-70.
[http://dx.doi.org/10.1016/j.foodchem.2014.05.118] [PMID:  25038688] 
[168] 
Gupta A, Kaur CD, Saraf S, Saraf S. Formulation, characterization, and evaluation of ligand-conjugated biodegradable quercetin nanoparticles for active targeting. Artif Cells Nanomed Biotechnol  2016; 44(3): 960-70.
[PMID:  25813566] 
[169] 
Lee HJ, Park HH, Sohn Y, et al. α-Galactosidase delivery using 30Kc19-human serum albumin nanoparticles for effective treatment of Fabry disease. Appl Microbiol Biotechnol  2016; 100(24): 10395-402.
[http://dx.doi.org/10.1007/s00253-016-7689-z] [PMID:  27353764] 
[170] 
Estrada LH, Chu S, Champion JA. Protein nanoparticles for intracellular delivery of therapeutic enzymes. J Pharm Sci  2014; 103(6): 1863-71.
[http://dx.doi.org/10.1002/jps.23974] [PMID:  24740820] 
[171] 
Yu X, Trase I, Ren M, Duval K, Guo X, Chen Z. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery. J Nanomater  2016; 2016: 15.
[http://dx.doi.org/10.1155/2016/1087250] [PMID:  27398083] 
[172] 
Jawahar N, Sn M. Polymeric nanoparticles for drug delivery and targeting : A comprehensive review. Int J Health Allied Sci  2012; 1(4): 1.
[http://dx.doi.org/10.4103/2278-344X.107832] 
[173] 
Crucho CIC, Barros MT. Polymeric nanoparticles: A study on the preparation variables and characterization methods. Mater Sci Eng C  2017; 80: 771-84.
[http://dx.doi.org/10.1016/j.msec.2017.06.004] [PMID:  28866227] 
[174] 
Mühlstein A, Gelperina S, Kreuter J. Development of nanoparticle-bound arylsulfatase B for enzyme replacement therapy of mucopolysaccharidosis VI. Pharmazie  2013; 68(7): 549-54.
[PMID:  23923636] 
[175] 
Tancini B, Tosi G, Bortot B, et al. Use of Polylactide-Co-Glycolide-Nanoparticles for Lysosomal Delivery of a Therapeutic Enzyme in Glycogenosis Type II Fibroblasts. J Nanosci Nanotechnol  2015; 15(4): 2657-66.
[http://dx.doi.org/10.1166/jnn.2015.9251] [PMID:  26353478] 
[176] 
Bourdenx M, Daniel J, Genin E, et al. Nanoparticles restore lysosomal acidification defects: Implications for Parkinson and other lysosomal-related diseases. Autophagy  2016; 12(3): 472-83.
[http://dx.doi.org/10.1080/15548627.2015.1136769] [PMID:  26761717] 
[177] 
Moghimi SM, Hunter AC, Murray JC. Long-circulating and target-specific nanoparticles: Theory to practice. Pharmacol Rev  2001; 53(2): 283-318.
[PMID:  11356986] 
[178] 
Salvalaio M, Rigon L, Belletti D, et al. Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders. PLoS One  2016; 11(5)e0156452
[http://dx.doi.org/10.1371/journal.pone.0156452] [PMID:  27228099] 
[179] 
Tosi G, Costantino L, Rivasi F, et al. Targeting the central nervous system: In vivo experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123. J Control Release  2007; 122(1): 1-9.
[http://dx.doi.org/10.1016/j.jconrel.2007.05.022] [PMID:  17651855] 
[180] 
Garnacho C, Serrano D, Muro S. A fibrinogen-derived peptide provides intercellular adhesion molecule-1-specific targeting and intraendothelial transport of polymer nanocarriers in human cell cultures and mice. J Pharmacol Exp Ther  2012; 340(3): 638-47.
[http://dx.doi.org/10.1124/jpet.111.185579] [PMID:  22160267] 
[181] 
Papademetriou IT, Garnacho C, Schuchman EH, Muro S. In vivo performance of polymer nanocarriers dually-targeted to epitopes of the same or different receptors. Biomaterials  2013; 34(13): 3459-66.
[http://dx.doi.org/10.1016/j.biomaterials.2013.01.069] [PMID:  23398883] 
[182] 
Garnacho C, Dhami R, Dziubla T, et al. Delivery of acidsphingolyelinase in normal and Niemman-Pick disease mice using intercellular adhesion molecule-1-targeted polymer nanocarriers. Pharmacol Exp Ther  2008; 325(2): 400-8.
[183] 
Garnacho C, Muro S. ICAM-1 targeting, intracellular trafficking, and functional activity of polymer nanocarriers coated with a fibrinogen-derived peptide for lysosomal enzyme replacement. J Drug Target  2017; 25(9-10): 786-95.
[http://dx.doi.org/10.1080/1061186X.2017.1349771] [PMID:  28665212] 
[184] 
Hsu J, Bhowmick T, Burks SR, Kao JP, Muro S. Enhancing biodistribution of therapeutic enzymes in vivo by modulating surface coating and concentration of ICAM-1-targeted nanocarriers. J Biomed Nanotechnol  2014; 10(2): 345-54.
[http://dx.doi.org/10.1166/jbn.2014.1718] [PMID:  24738342] 
[185] 
Hsu J, Northrup L, Bhowmick T, Muro S. Enhanced delivery of α-glucosidase for Pompe disease by ICAM-1-targeted nanocarriers: Comparative performance of a strategy for three distinct lysosomal storage disorders. Nanomedicine (Lond)  2012; 8(5): 731-9.
[http://dx.doi.org/10.1016/j.nano.2011.08.014] [PMID:  21906578] 
[186] 
Calderon AJ, Bhowmick T, Leferovich J, et al. Optimizing endothelial targeting by modulating the antibody density and particle concentration of anti-ICAM coated carriers. J Control Release  2011; 150(1): 37-44.
[http://dx.doi.org/10.1124/jpet.107.133298] [PMID:  18287213] 
[187] 
Mayer FQ, Adorne MD, Bender EA, et al. Laronidase-functionalized multiple-wall lipid-core nanocapsules: Promising formulation for a more effective treatment of mucopolysaccharidosis type I. Pharm Res  2015; 32(3): 941-54.
[http://dx.doi.org/10.1007/s11095-014-1508-y] [PMID:  25208876] 
[188] 
Ruiz de Garibay AP, Delgado D, Del Pozo-Rodríguez A, Solinís MÁ, Gascón AR. Multicomponent nanoparticles as nonviral vectors for the treatment of Fabry disease by gene therapy. Drug Des Devel Ther  2012; 6: 303-10.
[http://dx.doi.org/10.2147/DDDT.S36131] [PMID:  23118528] 
[189] 
Schuh RS, de Carvalho TG, Giugliani R, Matte U, Baldo G, Teixeira HF. Gene editing of MPS I human fibroblasts by co-delivery of a CRISPR/Cas9 plasmid and a donor oligonucleotide using nanoemulsions as nonviral carriers. Eur J Pharm Biopharm  2018; 122: 158-66.
[http://dx.doi.org/10.1016/j.ejpb.2017.10.017] [PMID:  29122734] 
[190] 
Meerovich I, Koshkaryev A, Thekkedath R, Torchilin VP. Screening and optimization of ligand conjugates for lysosomal targeting. Bioconjug Chem  2011; 22(11): 2271-82.
[http://dx.doi.org/10.1021/bc200336j] [PMID:  21913714] 
[191] 
Koshkaryev A, Thekkedath R, Pagano C, Meerovich I, Torchilin VP. Targeting of lysosomes by liposomes modified with octadecyl-rhodamine B. J Drug Target  2011; 19(8): 606-14.
[http://dx.doi.org/10.3109/1061186X.2010.550921] [PMID:  21275828] 
[192] 
Hamill KM, Wexselblatt E, Tong W, Esko JD, Tor Y. Delivery of cargo to lysosomes using GNeosomes. ed.^eds. Methods Mol Biol  2017; 1594: 151-63.
[http://dx.doi.org/10.1007/978-1-4939-6934-0_9] [PMID:  28456981] 
[193] 
Brown A, Patel S, Ward C, et al. PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder. Sci Rep  2016; 6: 31750.
[http://dx.doi.org/10.1038/srep31750] [PMID:  27572704] 
[194] 
Li X, Wu M, Pan L, Shi J. Tumor vascular-targeted co-delivery of anti-angiogenesis and chemotherapeutic agents by mesoporous silica nanoparticle-based drug delivery system for synergetic therapy of tumor. Int J Nanomedicine  2015; 11: 93-105.
[http://dx.doi.org/10.2147/IJN.S81156] [PMID:  26766908] 
[195] 
Hayashi T, Shinagawa M, Kawano T, Iwasaki T. Drug delivery using polyhistidine peptide-modified liposomes that target endogenous lysosome. Biochem Biophys Res Commun  2018; 501(3): 648-53.
[http://dx.doi.org/10.1016/j.bbrc.2018.05.037] [PMID:  29746864] 
[196] 
Schneider JL, Dingman RK, Balu-Iyer SV. Lipidic Nanoparticles Comprising Phosphatidylinositol Mitigate Immunogenicity and Improve Efficacy of Recombinant Human Acid Alpha-Glucosidase in a Murine Model of Pompe Disease. J Pharm Sci  2018; 107(3): 831-7.
[http://dx.doi.org/10.1016/j.xphs.2017.10.038] [PMID:  29102549] 
[197] 
Dos Santos Rodrigues B, Oue H, Banerjee A, Kanekiyo T, Singh J. Dual functionalized liposome-mediated gene delivery across triple co-culture blood brain barrier model and specific in vivo neuronal transfection. J Control Release  2018; 286: 264-78.
[http://dx.doi.org/10.1016/j.jconrel.2018.07.043] [PMID:  30071253] 
[198] 
Giannotti MI, Esteban O, Oliva M, García-Parajo MF, Sanz F. pH-responsive polysaccharide-based polyelectrolyte complexes as nanocarriers for lysosomal delivery of therapeutic proteins. Biomacromolecules  2011; 12(7): 2524-33.
[http://dx.doi.org/10.1021/bm2003384] [PMID:  21604696] 
[199] 
Song W, Soo Lee S, Savini M, Popp L, Colvin VL, Segatori L. Ceria nanoparticles stabilized by organic surface coatings activate the lysosome-autophagy system and enhance autophagic clearance. ACS Nano  2014; 8(10): 10328-42.
[http://dx.doi.org/10.1021/nn505073u] [PMID:  25315655] 
[200] 
Dekiwadia CD, Lawrie AC, Fecondo JV. Peptide-mediated cell penetration and targeted delivery of gold nanoparticles into lysosomes. J Pept Sci  2012; 18(8): 527-34.
[http://dx.doi.org/10.1002/psc.2430] [PMID:  22764089] 
[201] 
Schwendener RA, Schott H. Liposome Formulations of Hydrophobic Drugs. Methods Mol Biol  2017; 1522: 73-82.
[http://dx.doi.org/10.1007/978-1-4939-6591-5_6] [PMID:  27837531] 
[202] 
Bozzuto G, Molinari A. Liposomes as nanomedical devices. Int J Nanomedicine  2015; 10: 975-99.
[http://dx.doi.org/10.2147/IJN.S68861] [PMID:  25678787] 
[203] 
Pardridge W. Blood-brain barrier drug targeting: The future of brain drug development.  M Mol Interv 2003; pp. 90-105.
[204] 
Thekkedath R, Koshkaryev A, Torchilin VP. Lysosome-targeted octadecyl-rhodamine B-liposomes enhance lysosomal accumulation of glucocerebrosidase in Gaucher’s cells in vitro. Nanomedicine (Lond)  2013; 8(7): 1055-65.
[http://dx.doi.org/10.2217/nnm.12.138] [PMID:  23199221] 
[205] 
Vecsernyés M, Fenyvesi F, Bácskay I, Deli MA, Szente L, Fenyvesi É. Cyclodextrins, blood-brain barrier, and treatment of neurological diseases. Arch Med Res  2014; 45(8): 711-29.
[http://dx.doi.org/10.1016/j.arcmed.2014.11.020] [PMID:  25482528] 
[206] 
Cabrera I, Abasolo I, Corchero JL, et al. α-Galactosidase-A Loaded-Nanoliposomes with Enhanced Enzymatic Activity and Intracellular Penetration. Adv Healthc Mater  2016; 5(7): 829-40.
[http://dx.doi.org/10.1002/adhm.201500746] [PMID:  26890358] 
[207] 
Del Pozo-Rodríguez A, Solinís MÁ, Rodríguez-Gascón A. Applications of lipid nanoparticles in gene therapy. Eur J Pharm Biopharm  2016; 109: 184-93.
[http://dx.doi.org/10.1016/j.ejpb.2016.10.016] [PMID:  27789356] 
[208] 
Delgado D, del Pozo-Rodríguez A, Solinís MA, Rodríguez-Gascón A. Understanding the mechanism of protamine in solid lipid nanoparticle-based lipofection: The importance of the entry pathway. Eur J Pharm Biopharm  2011; 79(3): 495-502.
[http://dx.doi.org/10.1016/j.ejpb.2011.06.005] [PMID:  21726641] 
[209] 
Ruiz de Garibay AP, Solinís MA, del Pozo-Rodríguez A, Apaolaza PS, Shen JS, Rodríguez-Gascón A. Solid Lipid Nanoparticles as Non-Viral Vectors for Gene Transfection in a Cell Model of Fabry Disease. J Biomed Nanotechnol  2015; 11(3): 500-11.
[http://dx.doi.org/10.1166/jbn.2015.1968] [PMID:  26307832] 
[210] 
Stehr F, van der Putten H. Bridging NCL research gaps. Biochim Biophys Acta  2015; 1852(10 Pt B): 2324-8.
[http://dx.doi.org/10.1016/j.bbadis.2015.06.003] [PMID:  26056946] 
[211] 
Di Martino P, Censi R, Gigliobianco MR, et al. Nano-medicine Improving the Bioavailability of Small Molecules for the Prevention of Neurodegenerative Diseases. Curr Pharm Des  2017; 23(13): 1897-908.
[http://dx.doi.org/10.2174/1381612822666161227154447] [PMID:  28025942] 
Cite As
Current Pharmaceutical Design

New Advanced Strategies for the Treatment of Lysosomal Diseases Affecting the Central Nervous System

Abstract
