Gene Therapy Repairs for the Epileptic Brain: Potential for Treatment and Future Directions

被引:10
作者
Ahmad, Md A. [1 ]
Pottoo, Faheem H. [2 ]
Akbar, Md [3 ]
机构
[1] Integral Univ, Fac Pharm, Dept Pharmacol, Lucknow, Uttar Pradesh, India
[2] Imam Abdul Rahman Bin Faisal Univ, Coll Clin Pharm, Dept Pharmacol, POB 1982, Dammam 31441, Saudi Arabia
[3] Jamia Hamdard, Dept Pharmacol, Sch Pharmaceut Educ & Res, New Delhi 110062, India
关键词
Channelopathies; epilepsy; gene therapy; neuroprotection; status epilepticus; temporal lobe epilepsy; nonviral vector delivery; viral vector delivery; PHENOTYPIC SPECTRUM; GRIN2A MUTATIONS; VIRUS VECTORS; EPILEPSIES; SEIZURES; DELIVERY; TRANSPLANTATION; ENCEPHALOPATHY; RALOXIFENE; RECEPTORS;
D O I
10.2174/1566523220666200131142423
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Epilepsy is a syndrome specified by frequent seizures and is one of the most prevalent neurological conditions, and that one-third of people of epilepsy are resistant to available drugs. Surgery is supposed to be the main treatment for the remedy of multiple drug-resistant epilepsy, but it is a drastic procedure. Advancement in genomic technologies indicates that gene therapy can make such surgery unnecessary. The considerable number of new studies show the significance of mutation in mammalian target of rapamycin pathway, NMDA receptors, GABA receptors, potassium channels and G-protein coupled receptors. Illustration of the meticulous drug in epilepsy targeting new expression of mutations in SCN8A, GRIN2A, GRIN2D and KCNT1 are conferred. Various methods are utilized to express a gene in a precise area of the brain; Transplantation of cells in an ex vivo approach (fetal cells, fibroblasts, immortalized cells), nonviral vector delivery and viral vector delivery like retrovirus, herpes simplex virus adenovirus and adeno-related virus. Gene therapy has thus been explored to generate anti-epileptogenic, anti-seizure and disease-modifying effects. Specific targeting of the epileptogenic region is facilitated by gene therapy, hence sparing the adjacent healthy tissue and decreasing the adverse effects that frequently go hand in hand with antiepileptic medication.
引用
收藏
页码:367 / 375
页数:9
相关论文
共 68 条
[11]   Enhanced nigrostriatal neuron-specific, long-term expression by using neural-specific promoters in combination with targeted gene transfer by modified helper virus-free HSV-1 vector particles [J].
Cao, Haiyan ;
Zhang, Guo-rong ;
Wang, Xiaodan ;
Kong, Lingxin ;
Geller, Alfred I. .
BMC NEUROSCIENCE, 2008, 9 (1)
[12]   GRIN2A mutations cause epilepsy-aphasia spectrum disorders [J].
Carvill, Gemma L. ;
Regan, Brigid M. ;
Yendle, Simone C. ;
O'Roak, Brian J. ;
Lozovaya, Natalia ;
Bruneau, Nadine ;
Burnashev, Nail ;
Khan, Adiba ;
Cook, Joseph ;
Geraghty, Eileen ;
Sadleir, Lynette G. ;
Turner, Samantha J. ;
Tsai, Meng-Han ;
Webster, Richard ;
Ouvrier, Robert ;
Damiano, John A. ;
Berkovic, Samuel F. ;
Shendure, Jay ;
Hildebrand, Michael S. ;
Szepetowski, Pierre ;
Scheffer, Ingrid E. ;
Mefford, Heather C. .
NATURE GENETICS, 2013, 45 (09) :1073-+
[13]  
Chepurnov S. A., 2012, Uspekhi Fiziologicheskikh Nauk, V43, P55
[14]   Dominant KCNA2 mutation causes episodic ataxia and pharmacoresponsive epilepsy [J].
Corbett, Mark A. ;
Bellows, Susannah T. ;
Li, Melody ;
Carroll, Renee ;
Micallef, Silvana ;
Carvill, Gemma L. ;
Myers, Candace T. ;
Howell, Katherine B. ;
Maljevic, Snezana ;
Lerche, Holger ;
Gazina, Elena V. ;
Mefford, Heather C. ;
Bahlo, Melanie ;
Berkovic, Samuel F. ;
Petrou, Steven ;
Scheffer, Ingrid E. ;
Gecz, Jozef .
NEUROLOGY, 2016, 87 (19) :1975-1984
[15]   Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease [J].
Deacon, T ;
Schumacher, J ;
Dinsmore, J ;
Thomas, C ;
Palmer, P ;
Kott, S ;
Edge, A ;
Penney, D ;
Kassissieh, S ;
Dempsey, P ;
Isacson, O .
NATURE MEDICINE, 1997, 3 (03) :350-353
[16]   Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes [J].
Endele, Sabine ;
Rosenberger, Georg ;
Geider, Kirsten ;
Popp, Bernt ;
Tamer, Ceyhun ;
Stefanova, Irina ;
Milh, Mathieu ;
Kortuem, Fanny ;
Fritsch, Angela ;
Pientka, Friederike K. ;
Hellenbroich, Yorck ;
Kalscheuer, Vera M. ;
Kohlhase, Juergen ;
Moog, Ute ;
Rappold, Gudrun ;
Rauch, Anita ;
Ropers, Hans-Hilger ;
von Spiczak, Sarah ;
Toennies, Holger ;
Villeneuve, Nathalie ;
Villard, Laurent ;
Zabel, Bernhard ;
Zenker, Martin ;
Laube, Bodo ;
Reis, Andre ;
Wieczorek, Dagmar ;
Van Maldergem, Lionel ;
Kutsche, Kerstin .
NATURE GENETICS, 2010, 42 (11) :1021-U153
[17]   Cationic lipid-DNA complexes for gene therapy: Understanding the relationship between complex structure and gene delivery pathways at the molecular level [J].
Ewert, K ;
Slack, NL ;
Ahmad, A ;
Evans, HM ;
Lin, AJ ;
Samuel, CE ;
Safinya, CR .
CURRENT MEDICINAL CHEMISTRY, 2004, 11 (02) :133-149
[18]   Porcine xenografts in parkinson's disease and Huntington's disease patients: Preliminary results [J].
Fink, JS ;
Schumacher, JM ;
Ellias, SL ;
Palmer, EP ;
Saint-Hilaire, M ;
Shannon, K ;
Penn, R ;
Starr, P ;
VanHorne, C ;
Kott, HS ;
Dempsey, PK ;
Fischman, AJ ;
Raineri, R ;
Manhart, C ;
Dinsmore, J ;
Isacson, O .
CELL TRANSPLANTATION, 2000, 9 (02) :273-278
[19]   Generalized epilepsy in a family with basal ganglia calcifications and mutations in SLC20A2 and CHRNB2 [J].
Fjaer, Roar ;
Brodtkorb, Eylert ;
Oye, Ane-Marte ;
Sheng, Ying ;
Vigeland, Magnus Dehli ;
Kvistad, Kjell Arne ;
Backe, Paul Hoff ;
Selmer, Kaja Kristine .
EUROPEAN JOURNAL OF MEDICAL GENETICS, 2015, 58 (11) :624-628
[20]   Identification of new epilepsy treatments: Issues in preclinical methodology [J].
Galanopoulou, Aristea S. ;
Buckmaster, Paul S. ;
Staley, Kevin J. ;
Moshe, Solomon L. ;
Perucca, Emilio ;
Engel, Jerome, Jr. ;
Loescher, Wolfgang ;
Noebels, Jeffrey L. ;
Pitkanen, Asla ;
Stables, James ;
White, H. Steve ;
O'Brien, Terence J. ;
Simonato, Michele .
EPILEPSIA, 2012, 53 (03) :571-582