Current status of gene therapy for α-1 antitrypsin deficiency

Expert Opinion on Biological Therapy

Volumn 15, Issue 3, 2015, Pages 329-336

  Loring, Heather S ^a   Flotte, Terence R ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

Author keywords

Adeno associated virus; Emphysema; Gene therapy; Liver disease; Vectors; 1 antitrypsin

Indexed keywords

ADENOVIRUS VECTOR; ELASTIN; LEUKOCYTE ELASTASE; ALPHA 1 ANTITRYPSIN;

ADENO ASSOCIATED VIRUS; ALPHA 1 ANTITRYPSIN DEFICIENCY; ENZYME INHIBITION; GENE TRANSFER; HUMAN; LIMB PERFUSION; LUNG ALVEOLUS EPITHELIUM; LUNG LAVAGE; PLURIPOTENT STEM CELL; REVIEW; SUBSTITUTION THERAPY; TRANSGENE; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; VIRUS RECOMBINANT; ADENOVIRIDAE; ADMINISTRATION AND DOSAGE; ALPHA 1-ANTITRYPSIN DEFICIENCY; ANIMAL; CLINICAL TRIAL (TOPIC); GENE THERAPY; GENE VECTOR; GENETICS; PROCEDURES;

ADENO-ASSOCIATED VIRUS; ADENOVIRIDAE; IPS;

ADENOVIRIDAE; ALPHA 1-ANTITRYPSIN; ALPHA 1-ANTITRYPSIN DEFICIENCY; ANIMALS; CLINICAL TRIALS AS TOPIC; GENETIC THERAPY; GENETIC VECTORS; HUMANS; TRANSGENES;

EID: 84923084320     PISSN: 14712598     EISSN: 17447682     Source Type: Journal    
DOI: 10.1517/14712598.2015.978854     Document Type: Review

References (70)

1. Laurell CB, Eriksson S. The electrophoretic alpha1-globulin pattern of serum in alpha1-antitrypsin deficiency. 1963. COPD 2013;10(Suppl 1):3-8
2. Laurell CB, Eriksson S. The serum alpha-L-antitrypsin in families with hypo-alpha-L-antitrypsinemia. Clinica Chimica Acta 1965;1:395-8
3. Laurell CB, Eriksson S. [Hypo-alpha-1-antitrypsinemia]. Verh Dtsch Ges Inn Med 1964;70:537-9
4. Laurell CB, Eriksson S. The electrophoretic alpha-1-globulin pattern of serum in alpha-1 antitrypsin deficiency. Scand J Clin Lab Invest 1963;15:132-40
5. Crystal RG. The alpha 1-antitrypsin gene and its deficiency states. TIG 1989;5:411-17
6. Crystal RG, Brantly ML, Hubbard RC, et al. The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy. Chest 1989;95:196-208
7. Aarbiou J, Ertmann M, Van Wetering S, et al. Human neutrophil defensins induce lung epithelial cell proliferation in vitro. J Leukoc Biol 2002;72:167-74
8. Stoller JK, Aboussouan LS. A review of alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2012;185:246-59
9. Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 antitrypsin deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al. GeneReviews(R). University of Washington, Seattle, WA: 1993
10. Stockley RA. Proteolytic enzymes, their inhibitors and lung diseases. Clin Sci 1983;64:119-26
11. Stoller JK, Aboussouan LS. Alpha1-antitrypsin deficiency. Lancet 2005;365:2225-36
12. Crystal RG. Alpha 1-antitrypsin deficiency, emphysema, and liver disease. Genetic basis and strategies for therapy. J Clin Invest 1990;85:1343-52
13. Carrell RW, Whisstock J, Lomas DA. Conformational changes in serpins and the mechanism of alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med 1994;150:S171-5
14. Lomas DA, Evans DL, Finch JT, Carrell RW. The mechanism of Z alpha 1-antitrypsin accumulation in the liver. Nature 1992;357:605-7
15. Lomas DA, Carrell RW. A protein structural approach to the solution of biological problems: alpha 1-antitrypsin as a recent example. Am J Physiol 1993;265:L211-19
16. Lomas DA, Evans DL, Stone SR, et al. Effect of the Z mutation on the physical and inhibitory properties of alpha 1-antitrypsin. Biochemistry 1993;32:500-8
17. Llewellyn-Jones CG, Lomas DA, Carrell RW, Stockley RA. The effect of the Z mutation on the ability of alpha 1-antitrypsin to prevent neutrophil mediated tissue damage. Biochim Biophys Acta 1994;1227:155-60
18. Browne RJ, Mannino DM, Khoury MJ. Alpha 1-antitrypsin deficiency deaths in the United States from 1979-1991. An analysis using multiple-cause mortality data. Chest 1996;110:78-83
19. Eden E, Strange C, Holladay B, Xie L. Asthma and allergy in alpha-1 antitrypsin deficiency. Respir Med 2006;100:1384-91
20. Strange C. Airway disease in alpha-1 antitrypsin deficiency. COPD 2013;10(Suppl 1):68-73
21. Sharp HL, Mathis R, Krivit W, Freier E. The liver in noncirrhotic-1-antitrypsin deficiency. J Lab Clin Med 1971;78:1012-13
22. Lomas DA. Loop-sheet polymerization: the structural basis of Z alpha 1-antitrypsin accumulation in the liver. Clin Sci 1994;86:489-95
23. Sharp HL. Alpha-1-antitrypsin: an ignored protein in understanding liver disease. Semin Liver Dis 1982;2:314-28
24. Sharp HL. Wherefore art thou liver disease associated with alpha-1 antitrypsin deficiency? Hepatology 1995;22:666-8
25. Gadek JE, Klein HG, Holland PV, Crystal RG. Replacement therapy of alpha 1-antitrypsin deficiency. Reversal of protease-antiprotease imbalance within the alveolar structures of PiZ subjects. J Clin Invest 1981;68:1158-65
26. Gadek JE, Hunninghake GW, Fells GA, et al. Evaluation of the protease-antiprotease theory of human destructive lung disease. Bull Eur Physiopathol Respir 1980;16(Suppl):27-40
27. Gadek JE, Fells GA, Zimmerman RL, et al. Antielastases of the human alveolar structures. Implications for the protease-antiprotease theory of emphysema. J Clin Invest 1981;68:889-98
28. Gadek JE, Crystal RG. Experience with replacement therapy in the destructive lung disease associated with severe alpha-1-antitrypsin deficiency. Am Rev Respir Dis 1983;127:S45-6
29. Gadek JE, Fulmer JD, Gelfand JA, et al. Danazol-induced augmentation of serum alpha 1-antitrypsin levels in individuals with marked deficiency of this antiprotease. J Clin Invest 1980;66:82-7
30. Wewers MD, Casolaro MA, Sellers SE, et al. Replacement therapy for alpha 1-antitrypsin deficiency associated with emphysema. N Engl J Med 1987;316:1055-62
31. Hubbard RC, Crystal RG. Alpha-1-antitrypsin augmentation therapy for alpha-1-antitrypsin deficiency. Am J Med 1988;84:52-62
32. Bergin DA, Reeves EP, Hurley K, et al. The circulating proteinase inhibitor alpha-1 antitrypsin regulates neutrophil degranulation and autoimmunity. Sci Transl Med 2014;6:217ra211
33. Wewers MD, Casolaro MA, Crystal RG. Comparison of alpha-1-antitrypsin levels and antineutrophil elastase capacity of blood and lung in a patient with the alpha-1-antitrypsin phenotype null-null before and during alpha-1-antitrypsin augmentation therapy. Am Rev Respir Dis 1987;135:539-43
34. Hubbard RC, Sellers S, Czerski D, et al. Biochemical efficacy and safety of monthly augmentation therapy for alpha 1-antitrypsin deficiency. JAMA 1988;260:1259-64
35. Hubbard RC, Crystal RG. Augmentation therapy of alpha 1-antitrypsin deficiency. Eur Respir J Suppl 1990;9:44s-52s
36. Hubbard RC, Brantly ML, Sellers SE, et al. Anti-neutrophil-elastase defenses of the lower respiratory tract in alpha 1-antitrypsin deficiency directly augmented with an aerosol of alpha 1-antitrypsin. Ann Intern Med 1989;111:206-12
37. Hubbard RC, Casolaro MA, Mitchell M, et al. Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance. Proc Nat Acad Sci USA 1989;86:680-4
38. Hubbard RC, Crystal RG. Strategies for aerosol therapy of alpha 1-antitrypsin deficiency by the aerosol route. Lung 1990;168(Suppl):565-78
39. Mueller C, Flotte TR. Gene-based therapy for alpha-1 antitrypsin deficiency. COPD 2013;10(Suppl 1):44-49
40. Rosenfeld MA, Siegfried W, Yoshimura K, et al. Adenovirus-mediated transfer of a recombinant alpha 1-antitrypsin gene to the lung epithelium in vivo. Science 1991;252:431-4
41. Kay MA, Graham F, Leland F, Woo SL. Therapeutic serum concentrations of human alpha-1-antitrypsin after adenoviral-mediated gene transfer into mouse hepatocytes. Hepatology 1995;21:815-19
42. Brigham KL, Meyrick B, Christman B, et al. In vivo transfection of murine lungs with a functioning prokaryotic gene using a liposome vehicle. Am J Med Sci 1989;298:278-81
43. Canonico AE, Conary JT, Meyrick BO, Brigham KL. Aerosol and intravenous transfection of human alpha 1-antitrypsin gene to lungs of rabbits. Am J Respir Cell Mol Biol 1994;10:24-9
44. Brigham KL, Lane KB, Meyrick B, et al. Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy. Hum Gene Ther 2000;11:1023-32
45. Flotte TR, Berns KI. Adeno-associated virus: a ubiquitous commensal of mammals. Hum Gene Ther 2005;16:401-7
46. Mueller C, Flotte TR. Clinical gene therapy using recombinant adeno-associated virus vectors. Gene Ther 2008;15:858-63
47. Flotte TR. Gene therapy progress and prospects: recombinant adeno-associated virus (rAAV) vectors. Gene Ther 2004;11:805-10
48. Flotte TR, Afione SA, Conrad C, et al. Stable in vivo expression of the cystic fibrosis transmembrane conductance regulator with an adeno-associated virus vector. Proc Nat Acad Sci USA 1993;90:10613-17
49. Xiao W, Berta SC, Lu MM, et al. Adeno-associated virus as a vector for liver-directed gene therapy. J Virol 1998;72:10222-6
50. Song S, Morgan M, Ellis T, et al. Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors. Proc Nat Acad Sci USA 1998;95:14384-8
51. Song S, Laipis PJ, Berns KI, Flotte TR. Effect of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle. Proc Nat Acad Sci USA 2001;98:4084-8
52. Song S, Lu Y, Choi YK, et al. DNA-dependent PK inhibits adeno-associated virus DNA integration. Proc Nat Acad Sci USA 2004;101:2112-16
53. Flotte TR, Brantly ML, Spencer LT, et al. Phase I trial of intramuscular injection of a recombinant adeno-associated virus alpha 1-antitrypsin (rAAV2-CB-hAAT) gene vector to AAT-deficient adults. Hum Gene Ther 2004;15:93-128
54. Brantly ML, Spencer LT, Humphries M, et al. Phase I trial of intramuscular injection of a recombinant adeno-associated virus serotype 2 alphal-antitrypsin (AAT) vector in AAT-deficient adults. Hum Gene Ther 2006;17:1177-86
55. Lu Y, Choi YK, Campbell-Thompson M, et al. Therapeutic level of functional human alpha 1 antitrypsin (hAAT) secreted from murine muscle transduced by adeno-associated virus (rAAV1) vector. J Gene Med 2006;8:730-5
56. Flotte TR, Conlon TJ, Poirier A, et al. Preclinical characterization of a recombinant adeno-associated virus type 1-pseudotyped vector demonstrates dose-dependent injection site inflammation and dissemination of vector genomes to distant sites. Hum Gene Ther 2007;18:245-56
57. Brantly ML, Chulay JD, Wang L, et al. Sustained transgene expression despite T lymphocyte responses in a clinical trial of rAAV1-AAT gene therapy. Proc Nat Acad Sci USA 2009;106:16363-8
58. Flotte TR, Trapnell BC, Humphries M, et al. Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing alpha1-antitrypsin: interim results. Hum Gene Ther 2011;22:1239-47
59. Chulay JD, Ye GJ, Thomas DL, et al. Preclinical evaluation of a recombinant adeno-associated virus vector expressing human alpha-1 antitrypsin made using a recombinant herpes simplex virus production method. Hum Gene Ther 2011;22:155-65
60. Mueller C, Chulay JD, Trapnell BC, et al. Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression. J Clin Invest 2013;123:5310-18
61. Nathwani AC, Tuddenham EG, Rangarajan S, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med 2011;365:2357-65
62. Flotte TR, Goetzmann J, Caridi J, et al. Apparently nonspecific enzyme elevations after portal vein delivery of recombinant adeno-associated virus serotype 2 vector in hepatitis C virus-infected chimpanzees. Hum Gene Ther 2008;19:681-9
63. Crystal RG, McElvaney NG, Rosenfeld MA, et al. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nat Genet 1994;8:42-51
64. De B, Heguy A, Leopold PL, et al. Intrapleural administration of a serotype 5 adeno-associated virus coding for alpha1-antitrypsin mediates persistent, high lung and serum levels of alpha1-antitrypsin. Mol Ther 2004;10:1003-10
65. De BP, Heguy A, Hackett NR, et al. High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses. Mol Ther 2006;13:67-76
66. Liqun Wang R, McLaughlin T, Cossette T, et al. Recombinant AAV serotype and capsid mutant comparison for pulmonary gene transfer of alpha-1-antitrypsin using invasive and noninvasive delivery. Mol Ther 2009;17:81-7
67. Flotte TR, Fischer AC, Goetzmann J, et al. Dual reporter comparative indexing of rAAV pseudotyped vectors in chimpanzee airway. Molecular therapy: the journal of the American Society of Gene Therapy 2010;18:594-600
68. Wilson AA, Murphy GJ, Hamakawa H, et al. Amelioration of emphysema in mice through lentiviral transduction of long-lived pulmonary alveolar macrophages. J Clin Invest 2010;120:379-89
69. Mueller C, Tang Q, Gruntman A, et al. Sustained miRNA-mediated knockdown of mutant AAT with simultaneous augmentation of wild-type AAT has minimal effect on global liver miRNA profiles. Mol Ther 2012;20:590-600
70. Gaudet D, Methot J, Dery S, et al. Efficacy and long-term safety of alipogene tiparvovec (AAV1-LPLS447X) gene therapy for lipoprotein lipase deficiency: an open-label trial. Gene Ther 2013;20:361-9