Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge
Authors:
Ľ. Ďuďáková 1*; B. Kousal 1,2*; H. Kolářová 1; L. Hlavatá 1,3; P. Lišková 1,2
Authors place of work:
Ústav dědičných metabolických poruch, 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice, Praha, přednosta prof. MUDr. Viktor Kožich, CSc.
1; Oční klinika, 1. lékařská fakulta, Univerzita Karlova v Praze a Všeobecná fakultní nemocnice, Praha, přednostka doc. MUDr. Jarmila Heissigerová, Ph. D., MBA
2; Oční klinika JL, s. r. o., primář doc. MUDr. Ján Lešták, CSc., FEBO, MBA, LL. A, DBA, FAOG
3
Published in the journal:
Čes. a slov. Oftal., 72, 2016, No. 4, p. 128-136
Category:
Original Article
Summary
The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.
The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.
Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.
Key words:
gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease
Zdroje
1. Acland, GM., Aguirre, GD., Ray J.,et al.: Gene therapy restores vision in a canine model of childhood blindness. Nat Genet, 28; 2001: 92–5.
2. Allikmets, R., Shroyer, NF., Singh, N.,et al.: Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science, 277; 1997: 1805–7.
3. Alory, C., Balch, WE.: Organization of the Rab-GDI/CHM superfamily: the functional basis for choroideremia disease. Traffic, 2; 2001: 532–43.
4. Anand, V., Barral, DC., Zeng, Y., et al.: Gene therapy for choroideremia: in vitro rescue mediated by recombinant adenovirus. Vision Res, 43; 2003: 919–26.
5. Bainbridge, JW., Mehat, MS., Sundaram, V., et al.: Long-term effect of gene therapy on Leber‘s congenital amaurosis. N Engl J Med, 372; 2015: 1887–97.
6. Bainbridge, JW., Smith, AJ., Barker, SS., et al.: Effect of gene therapy on visual function in Leber‘s congenital amaurosis. N Engl J Med, 358; 2008: 2231–39.
7. Bessis, N., GarciaCozar, FJ., Boissier MC.: Immune responses to gene therapy vectors: influence on vector function and effector mechanisms. Gene Ther, 11 Suppl 1; 2004: S10–7.
8. Boye, SE., GarciaCozar, FJ., Boissier, MC.: A comprehensive review of retinal gene therapy. Mol Ther, 21; 2013: 509–19.
9. Carelli, V., La Morgia, C., Valentino, ML., et al.: Retinal ganglion cell neurodegeneration in mitochondrial inherited disorders. Biochim Biophys Acta, 1787; 2009: 518–28.
10. Cideciyan, AV.: Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Prog Retin Eye Res, 29; 2010: 398–427.
11. Conlon, TJ., Deng, WT., Erger, K., et al.: Preclinical potency and safety studies of an AAV2-mediated gene therapy vector for the treatment of MERTK associated retinitis pigmentosa. Hum Gene Ther Clin Dev, 24; 2013: 23–8.
12. D‘Cruz, PM., Yasumura, D., Weir, J., et al.: Mutation of the receptor tyrosine kinase gene Mertk in the retinal dystrophic RCS rat. Hum Mol Genet, 9; 2000: 645-51.
13. Deng, WT., Dinculescu, A., Li, Q., et al.: Tyrosine-mutant AAV8 delivery of human MERTK provides long-term retinal preservation in RCS rats. Invest Ophthalmol Vis Sci, 53; 2012: 1895–1904.
14. Dimopoulos, IS., Chan, S., MacLaren, RE., et al.: Pathogenic mechanisms and the prospect of gene therapy for choroideremia. Expert Opin Orphan Drugs, 3; 2015: 787–98.
15. Ellouze, S., Augustin, S., Bouaita, A., et al.: Optimized allotopic expression of the human mitochondrial ND4 prevents blindness in a rat model of mitochondrial dysfunction. Am J Hum Genet, 83; 2008: 373–87.
16. Espinos, C., Millan, JM., Beneyto, M., et al.: Epidemiology of Usher syndrome in Valencia and Spain. Community Genet, 1; 1998: 223–8.
17. George, ND., Yates, JR., Moore, AT.: X linked retinoschisis. Br J Ophthalmol, 79; 1995: 697–702.
18. Gu, SM., Thompson, DA., Srikumari, CR., et al.: Mutations in RPE65 cause autosomal recessive childhood-onset severe retinal dystrophy. Nat Genet, 17; 1997: 194–7.
19. Guy, J., Qi, X., Koilkonda, RD., et al.: Efficiency and safety of AAV-mediated gene delivery of the human ND4 complex I subunit in the mouse visual system. Invest Ophthalmol Vis Sci, 50; 2009: 4205–14.
20. Han, Z., Conley, SM., Makkia, RS., et al.: DNA nanoparticle-mediated ABCA4 delivery rescues Stargardt dystrophy in mice. J Clin Invest, 122; 2012: 3221–6.
21. Hashimoto, T., Gibbs, D., Lillo, C., et al.: Lentiviral gene replacement therapy of retinas in a mouse model for Usher syndrome type 1B. Gene Ther, 14; 2007: 584–94.
22. Hauswirth, WW., Aleman, TS., Kaushal, S., et al.: Treatment of leber congenital amaurosis due to RPE65 mutations by ocular subretinal injection of adeno-associated virus gene vector: short-term results of a phase I trial. Hum Gene Ther, 19; 2008: 979–90.
23. Chacon-Camacho, OF., Zenteno, JC.: Review and update on the molecular basis of Leber congenital amaurosis. World J Clin Cases, 3; 2015: 112–24.
24. Kao, LS., Tyson, JE., Blakely, ML., et al.: Clinical research methodology I: introduction to randomized trials. J Am Coll Surg, 206; 2008: 361–9.
25. Kaufmann, KB., Buning, H., Galy, A., et al.: Gene therapy on the move. EMBO Mol Med, 5; 2013: 1642–61.
26. Kay, MA., Glorioso, JC., Naldini, L.: Viral vectors for gene therapy: the art of turning infectious agents into vehicles of therapeutics. Nat Med, 7; 2001: 33–40.
27. Kohl, S., Varsanyi, B., Antunes, GA., et al.: CNGB3 mutations account for 50% of all cases with autosomal recessive achromatopsia. Eur J Hum Genet, 13; 2005: 302–8.
28. Komaromy, AM., Alexander, JJ., Rowlan, JS., et al.: Gene therapy rescues cone function in congenital achromatopsia. Hum Mol Genet, 19; 2010: 2581–93.
29. Kong, J., Kim, SR., Binley, K., et al.: Correction of the disease phenotype in the mouse model of Stargardt disease by lentiviral gene therapy. Gene Ther, 15; 2008: 1311–20.
30. Kotterman, MA., Yin, L., Strazzeri, JM., et al.: Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates. Gene Ther, 22; 2015: 116–26.
31. Leber, T.: Ueber hereditäre und congenital-angelegte Sehnervenleiden [About hereditary and congenital optic nerve disorders]. Albrecht Von Graefes Arch Klin Exp Ophthalmol, 17; 1871: 249–91.
32. Lois, N., Holder, GE., Bunce, C., et al.: Phenotypic subtypes of Stargardt macular dystrophy-fundus flavimaculatus. Arch Ophthalmol, 119; 2001: 359–69.
33. Lopes, VS., Gibbs, D., Libby, RT., et al.: The Usher 1B protein, MYO7A, is required for normal localization and function of the visual retinoid cycle enzyme, RPE65. Hum Mol Genet, 20; 2011: 2560–70.
34. MacDonald IM., Hume S., Chan S., et al.: Choroideremia. GeneReviews® [online]. 2003-2015 [cit. 11. dubna 2016]. Dostupný z WWW: < http://www.ncbi.nlm.nih.gov/books/NBK1337/>.
35. Maguire, AM., Simonelli, F., Pierce, EA., et al.: Safety and efficacy of gene transfer for Leber‘s congenital amaurosis. N Engl J Med, 358; 2008: 2240–48.
36. Mali, S.: Delivery systems for gene therapy. Indian J Hum Genet, 19; 2013: 3-8.
37. Martin, KR., Quigley, HA.: Gene therapy for optic nerve disease. Eye (Lond), 18; 2004: 1049–55.
38. Meighan, PC., Peng, C., Varnum, MD.: Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels. Front Physiol, 6; 2015: 177.
39. Millan, JM., Aller, E., Jaijo, T., et al.: An update on the genetics of usher syndrome. J Ophthalmol, 2011; 2011: 417217.
40. Misra, S.: Human gene therapy: a brief overview of the genetic revolution. J Assoc Physicians India, 61; 2013: 127–33.
41. Molday, LL., Hicks, D., Sauer, CG., et al.: Expression of X-linked retinoschisis protein RS1 in photoreceptor and bipolar cells. Invest Ophthalmol Vis Sci, 42; 2001: 816–25.
42. Mukherjee, S., Thrasher, AJ.: Gene therapy for PIDs: progress, pitfalls and prospects. Gene, 525; 2013: 174–81.
43. Newman, NJ.: Hereditary optic neuropathies: from the mitochondria to the optic nerve. Am J Ophthalmol, 140; 2005: 517–23.
44. Ostergaard, E., Duno, M., Batbayli, M., et al.: A novel MERTK deletion is a common founder mutation in the Faroe Islands and is responsible for a high proportion of retinitis pigmentosa cases. Mol Vis, 17; 2011: 1485–92.
45. Prenner, JL., Capone Jr., A., Ciaccia, S., et al.: Congenital X-linked retinoschisis classification system. Retina, 26; 2006: S61–4.
46. Rivera, A., White, K., Stohr, H., et al.: A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration. Am J Hum Genet, 67; 2000: 800–13.
47. Roman, AJ., Cideciyan, AV., Aleman, TS., et al.: Full-field stimulus testing (FST) to quantify visual perception in severely blind candidates for treatment trials. Physiol Meas, 28; 2007: N51–6.
48. Sibbald, B.: Death but one unintended consequence of gene-therapy trial. CMAJ, 164; 2001: 1612.
49. Steinkuller, PG., Du, L., Gilbert, C., et al.: Childhood blindness. J AAPOS, 3; 1999: 26–32.
50. Thiadens, AA., Somervuo, V., van den Born, LI., et al.: Progressive loss of cones in achromatopsia: an imaging study using spectral-domain optical coherence tomography. Invest Ophthalmol Vis Sci, 51; 2010: 5952–7.
51. Tolmachova, T., Tolmachov, OE., Wavre-Shapton, ST., et al.: CHM/REP1 cDNA delivery by lentiviral vectors provides functional expression of the transgene in the retinal pigment epithelium of choroideremia mice. J Gene Med, 14; 2012: 158–68.
52. Tschernutter, M., Schlichtenbrede, FC., Howe, S., et al.: Long-term preservation of retinal function in the RCS rat model of retinitis pigmentosa following lentivirus-mediated gene therapy. Gene Ther, 12; 2005: 694–701.
53. Veleri, S. Lazar, CH., Chang, B., et al.: Biology and therapy of inherited retinal degenerative disease: insights from mouse models. Dis Model Mech, 8; 2015:109–29.
54. Verma, IM., Somia N.: Gene therapy -- promises, problems and prospects. Nature, 389; 1997: 239–42.
55. Wan, X., Fei, H., Zhao, MJ., et. al.: Efficacy and safety of RAAVZ-NDY treatment for leber´s hereditary optic neuropathy. Sci Rep, 19; 2016: 1–10.
56. Wang, D., Gao, G.: State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications. Discov Med, 18; 2014: 151–61.
57. Weng, J., Mata, NL., Azarian, SM., et al.: Insights into the function of Rim protein in photoreceptors and etiology of Stargardt‘s disease from the phenotype in abcr knockout mice. Cell, 98; 1999: 13–23.
Štítky
OphthalmologyČlánok vyšiel v časopise
Czech and Slovak Ophthalmology
2016 Číslo 4
Najčítanejšie v tomto čísle
- Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge
- Haemangiomas are Common Benign Tumors of the Child
- New Diagnostic Imaging Technique – Shear Wave Elastography
- Ocular Motility Disorders with Diplopia Like the first Symptoms of Paranasal Tumours with Orbital Invasion – a Case Report