Join us   Log in  

PHARMASPIRE - Volume 10, Issue 3, July - September, 2018

Pages: 107-112

Date of Publication: 14-Jun-2022

Print Article   Download XML  Download PDF

Gene therapy as a potential tool for neurodegenerative disorders: Possible highlights

Author: Raman Kumar Tripathi, Arti Rana, Shamsher Singh

Category: Pharmaceutics


Gene therapy is the transmission of genes into the patient to treat the illness. Gene can be transferred through somatic and germline techniques. In the somatic type of gene therapy, the genes are transmitted in the germ cells or stem cells whereas in germline gene therapy the genes are transmitted in the DNA or genome so it can pass to the offspring. The carriers used in this purpose are viral and non-viral vectors. Basically, these viral and non-viral carriers help to transfer the genes which further show its expression either by synthesizing proteins or causing mutation of DNA. Gene therapy is used in the cure or management of monogenic disorders and polygenic disorders; moreover, it is also a potential target for neurological disorders like in Alzheimer disease (AD) using gene therapy it is possible to inhibit, the progression of amyloidbeta peptide, a protein which causes amyloid plaques. Similarly, in Parkinson disease, the transfer of Neurturin, an analog of glial cell line-derived neurotrophic factor helps in survival of the dopaminergic neurons. In Huntington’s disease (HD), ASOS is used in the gene silencing which forms the protein known as Huntingtin. The HD may also be cured by the Casper cas 9 therapy. It would edit the DNA so that it will not make Huntingtin protein by transcription, thus treating the disease. By using this technique it’s useful to treat various disorders as genetic predisposition or in which the available drugs are unable to prevent or treat such problems as neurological and some of the non-neurological.

Keywords: Alzheimer disease, Crispr Cas9 Therapy, gene therapy, Parkinson’s disease


1. Kennedy EM, Cullen BR. Gene editing: A new tool for viral disease. Annu Rev Med 2017;68:401-11.

2. Brzezia-nska E, Doma-nska D, Jegier A. Gene doping in sport–perspectives and risks. Biol Sport 2014;31:251.

3. Vectors: A survey of molecular cloning vectors and their uses. Biotechnology 1988;10:1-578.

4. Wirth T, Parker N, Ylä-Herttuala S. History of gene therapy. Gene 2013;525:162-9.

5. Orkin SH, Reilly P. MEDICINE. Paying for future success in gene therapy. Science 2016;352:1059-61.

6. Gyngell C, Douglas T, Savulescu J. The ethics of germline gene editing. J Appl Philos 2017;34:498-513.

7. Reed G. How Your Genome Affects Your Life: The Societal Impact of Cutting Edge Genetics; 2016.

8. Johnson P, Martuza RL, Rabkin SD, Todo T. The General Hospital Corporation, Georgetown University and Catherex, Inc. Viral Vectors and Their Use in Therapeutic Methods. U.S. Patent. 2017, 20,170,290,908.

9. Choudhury SR, Hudry E, Maguire CA, Sena-Esteves M, Breakefield XO, Grandi P, et al. Viral vectors for therapy of neurologic diseases. Neuropharmacology 2017;120:63-80.

10. Naldini L. Gene therapy returns to centre stage. Nature 2015;526:351-60.

11. Yin H, Kanasty RL, Eltoukhy AA, Vegas AJ, Dorkin JR, Anderson DG, et al. Non-viral vectors for gene-based therapy. Nat Rev Genet 2014;15:541-55.

12. Hardee CL, Arévalo-Soliz LM, Hornstein BD, Zechiedrich L. Advances in nonviral DNA vectors for gene therapy. Genes (Basel) 2017;8:65.

13. Watanabe H, Gubbiotti A, Chinappi M, Takai N, Tanaka K, Tsumoto K, et al. Analysis of pore formation and protein translocation using large biological nanopores. Anal Chem 2017;89:11269-77.

14. Shapiro G, Wong AW, Bez M, Yang F, Tam S, Even L, et al. Multiparameter evaluation of in vivo gene delivery using ultrasound-guided, microbubbleenhanced sonoporation. J Control Release 2016;223:157-64.

15. Junquera E, Aicart E. Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors. Adv Colloid Interface Sci 2016;233:161-75.

16. Ramamoorth M, Narvekar A. Non viral vectors in gene therapy- an overview. J Clin Diagn Res 2015;9:GE01-6.

17. Alzheimer’s A. Alzheimer’s disease facts and figures. J Alzheimer’s Assoc 2015;11:332.

18. Lauzon MA, Daviau A, Marcos B, Faucheux N. Nanoparticle-mediated growth factor delivery systems: A new way to treat Alzheimer’s disease. J Control Release 2015;206:187-205.

19. Hardy J, De Strooper B. Alzheimer’s disease: Where next for anti-amyloid therapies? Brain 2017;140:853-5.

20. Liu Y, An S, Li J, Kuang Y, He X, Guo Y, et al. Brain-targeted co-delivery of therapeutic gene and peptide by multifunctional nanoparticles in Alzheimer’s disease mice. Biomaterials 2016;80:33-45.

21. Glat MJ, Offen D. Cell and gene therapy in Alzheimer’s disease. Stem Cells Dev 2013;22:1490-6.

22. Tuszynski MH, Yang JH, Barba D, U HS, Bakay RA, Pay MM, et al. Nerve growth factor gene therapy: Activation of neuronal responses in Alzheimer disease. JAMA Neurol 2015;72:1139-47.

23. Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L, et al. Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 2013;368:610-22.

24. Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release 2015;207:18-30.

25. Kordower JH, Bjorklund A. Trophic factor gene therapy for Parkinson’s disease. Mov Disord 2013;28:96-109.

26. Kirik D, Cederfjäll E, Halliday G, Petersén Å. Gene therapy for Parkinson’s disease: Disease modification by GDNF family of ligands. Neurobiol Dis 2017;97:179-88.

27. Blits B, Petry H. Perspective on the road toward gene therapy for parkinson disease. Front Neuroanat 2017;10:128.

28. Bankiewicz K, San Sebastian W, Samaranch L, Forsayeth J. GDNF and AADC Gene Therapy for Parkinson’s Disease. Translational Neuroscience. US: Springer; 2016. p. 6588.

29. Warren Olanow C, Bartus RT, Baumann TL, Factor S, Boulis N, Stacy M, et al. Gene delivery of neurturin to putamen and substantia Nigra in Parkinson disease: A double-blind, randomized, controlled trial. Ann Neurol 2015;78:248-57.

30. Ross CA, Aylward EH, Wild EJ, Langbehn DR, Long JD, Warner JH, et al. Huntington disease: Natural history, biomarkers and prospects for therapeutics. Nat Rev Neurol 2014;10:204-16.

31. Godinho BM, Malhotra M, O’Driscoll CM, Cryan JF. Delivering a diseasemodifying treatment for Huntington’s disease. Drug Discov Today 2015;20:50-64.

32. Glorioso JC, Cohen JB, Carlisle DL, Munoz-Sanjuan I, Friedlander RM. Moving toward a gene therapy for Huntington’s disease. Gene Ther 2015;22:931-3.

33. Zlotorynski E. Genome engineering: NHEJ and CRISPR-cas9 improve gene therapy. Nat Rev Mol Cell Biol 2016;18:4.

34. Xiao-Jie L, Hui-Ying X, Zun-Ping K, Jin-Lian C, Li-Juan J. CRISPR-cas9: A new and promising player in gene therapy. J Med Genet 2015;52:289-96.

35. Southwell AL, Skotte NH, Caron N, Kordasiewicz H, Oestergaard M, Doty CN, et al. 696. Pre-clinical evaluation of allele-specific mutant huntingtin gene silencing antisense oligonucleotides. Mol Ther 2015;23:S277.

36. Kolli N, Lu M, Maiti P, Rossignol J, Dunbar GL. CRISPR-cas9 mediated genesilencing of the mutant huntingtin gene in an in vitro model of Huntington’s disease. Int J Mol Sci 2017;18.