Drugs for gene therapy: features of usage in geriatrics and pediatrics

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Abstract


Advances in modern medicine and biotechnology allow specialists to adjust the patient’s proteome and metabolome. Gene engineering allows us to create drugs that affect the cause of the disease at the level of gene expression. Thus, not the links of pathogenesis or the symptom of the disease are subjected to correction, but the trigger itself, a defective gene that provokes a cascade of pathological processes. According to the definition of the State Pharmacopoeia, gene therapeutic drugs are drugs whose pharmaceutical substance is a recombinant nucleic acid or includes a recombinant nucleic acid that allows for the regulation, repair, replacement, addition or removal of a genetic sequence. The article reflects all available, developed and used in real clinical practice gene therapy drugs of russian and foreign production. The mechanisms of action, features of the use of these drugs in pediatric and geriatric practice, as well as existing problems and limitations of their use, including deontological issues, are noted.


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About the authors

Konstantin G. Gurevich

Evdokimov Moscow State University of Medicine and Dentistry of the Ministry of Healthcare of the Russian Federation

Author for correspondence.
Email: zwx@inbox.ru

Russian Federation, Moscow

Dr. Med. Sci., Professor, Head of the UESCO Dept. of Health as a Life Style and Development, Faculty of Pedagogic Education in Medical School

Yulya A. Sorokina

Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation

Email: urakoval@live.ru

Russian Federation, Nizhny Novgorod

PhD, Assistant Professor, Dept. of General and Clinical Pharmacology

Alexander L. Urakov

Izhevsk State Medical Academy of the Ministry of Health of the Russian Federation

Email: urakoval@live.ru

Russian Federation, Izhevsk

Dr. Med. Sci., Professor and Head, Dept. of General and Clinical Pharmacology

Darya M. Gavrilova

Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation

Email: lovcovalubov@mail.ru

Russian Federation, Nizhny Novgorod

Student

Lyubov V. Lovtsova

Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation

Email: lovcovalubov@mail.ru

Russian Federation, Nizhny Novgorod

Dr. Med. Sci., Assistant Professor and Head, Dept. of General and Clinical Pharmacology

Olga V. Zanozina

Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation

Email: zwx2@mail.ru

Russian Federation, Nizhny Novgorod

Dr. Med. Sci., Professor; Dr. Med. Sci., Professor, Dept. of Hospital Therapy, Head, Division of Endocrinology

References

  1. Ураков А.Л., Гуревич К.Г., Сорокина Ю.А., и др. Взаимосвязь клинической эффективности сахароснижающих препаратов, микробиоты кишечника, рациона питания и генотипа пациента при сахарном диабете 2-го типа // Обзоры по клинической фармакологии и лекарственной терапии. – 2018. – Т. 16. – № 4. – С. 11–18. [Urakov AL, Gurevich KG, Sorokina IA, et al. Relationship of clinical efficacy of glucose lowering agents, gut microbiota, diet, and patient’s genotype in diabetes mellitus type 2. Reviews on clinical pharmacology and drug therapy. 2018;4(16):11-18. (In Russ.)]. https://doi.org/10.17816/RCF16411-18.
  2. MIT NEWDIGS FoCUS Project. Existing gene therapy pipeline likely to yield dozens of approved products within five years. 2017.
  3. Государственная фaрмакопея Российской Федерации. ОФС 1.9.1.0001.18 Генотерапевтические лекарственные препараты и методы их анализа. Генотерапевтические лекарственные препараты. 2018. [Gosudarstvennaya farmakopeya Rossiiskoi Federatsii. OFS1.9.1.0001.18 Genoterapevticheskie lekarstvennye preparaty i metody ikh analiza. Genoterapevticheskie lekarstvennye preparaty. 2018. (In Russ.)]
  4. Zhang WW, Li J, Li D, et al. The first approved gene therapy product for cancer Ad-p53 (Gendicine): 12 years in the clinic. Hum Gene Ther. 2018;29(2):160-179. https://doi.org/10.1089/hum.2017.218.
  5. Xia Y, Du Z, Wang X, Li X. Treatment of Uterine Sarcoma with rAd-p53 (Gendicine) Followed by Chemotherapy: Clinical Study of TP53 Gene Therapy. Hum Gene Ther. 2018;29(2):242-250. https://doi.org/10.1089/hum. 2017.206.
  6. Li Y, Li B, Li CJ, Li LJ. Key points of basic theories and clinical practice in rAd-p53 (Gendicine™) gene therapy for solid malignant tumors. Expert Opin Biol Ther. 2015;15(3): 437-454. https://doi.org/10.1517/14712598.2015.990882.
  7. Liang M. Oncorine, the World First Oncolytic Virus Medicine and its Update in China. Curr Cancer Drug Targets. 2018;18(2):171-176. https://doi.org/10.2174/1568009618666171129221503
  8. Wie D, Xu J, Liu XY, et al. Fighting Cancer with Viruses: Oncolytic Virus Therapy in China. Hum Gene Ther. 2018;29(2): 151-159. https://doi.org/10.1089/hum.2017.212.
  9. Gangi A, Zager JS. The safety of talimogene laherparepvec for the treatment of advanced melanoma. Expert Opin Drug Saf. 2017;16(2):265-269. https://doi.org/10.1080/14740338.2017.1274729.
  10. Naqash AR, Stroud G, Collichio FA, et al. Metastatic melanoma in a 95 years old patient responding to treatment with talimogene laherparepvec followed by nivolumab. Acta Oncol. 2017;56(10):1327-1330. https://doi.org/10.1080/0284186X.2017.1324212.
  11. Novartis.com [Internet]. Novartis submits application to FDA for KymriahTM (tisagenlecleucel) in adult patients with r/r DLBCL, seeking second indication for first-ever FDA approved CAR-T therapy [updated 2017 Oсt 31; cited 2019 Sep 27]. Available from: https://www.novartis.com/news/media-releases/novartis-submits-application-fda-kymriahtm-tisagenlecleucel-adult-patients-rr-dlbcl-seeking-second-indication-first-ever-fda-approved-car-t-therapy.
  12. Ema.europa.eu [Internet]. Yescarta [updated 2018 Nov 23; cited 2019 Sep27]. Available from: https://www.ema.europa.eu/documents/product-information/yescarta-epar-product-information_en.pdf.
  13. FDA. Luxturna. Highlights of prescribing information. Spark Therapeutics; 2017.
  14. Аляутдин Р.Н., Романов Б.К., Переверзев А.П., и др. Алипоген типарвовек: долгая дорога к оценке отношения пользы и риска генетических препаратов // Ведомости Научного центра экспертизы средств медицинского применения. – 2015. – № 1. – С. 31–34. [Alyautdin RN, Romanov BK, Pereverzev AP, et al. Alipogene tiparvovec: a long journey of risk-benefit ratio assessment of gene therapy products. Vedomosti Nauchnogo tsentra ekspertizy sredstv meditsinskogo primeneniya. 2015;(1):31-34.(In Russ.)]
  15. Gaudet D, Stroes ES, Méthot J, et al. Long-Term Retrospective Analysis of Gene Therapy with Alipogene Tiparvovec and Its Effect on Lipoprotein Lipase Deficiency-Induced Pancreatitis. Hum Gene Ther. 2016;27(11):916-925. https://doi.org/10.1089/hum.2015.158.
  16. Zolgensma.com [Internet]. Important Safety Information [updated 2019 Jun; cited 2019 Sep27]. Available from: https://www.zolgensma.com/.
  17. Al-Zaidy SA, Mendell JR. From Clinical Trials to Clinical Practice: Practical Considerations for Gene Replacement Therapy in SMA Type 1. Pediatr Neurol. 2019;100:3-11. https://doi.org/10.1016/j.pediatrneurol.2019.06.007.
  18. «Зингтело»: генная терапия бета-талассемии. mosmedpreparaty.ru [интернет]. Доступно по: https://mosmedpreparaty.ru/news/17297. Ссылка активна на 07.08.2020. [“Zingtelo”: gennaya terapiya beta-talassemii. Mosmedpreparaty.ru [Internet]. (In Russ.)]
  19. Швальб А.В., Гавриленко А.В., Калинин Р.Е., и др. Эффективность и безопасность применения препарата «Неоваскулген» в комплексной терапии пациентов с хронической ишемией нижних конечностей (Iib–III фаза клинических испытаний) // Клеточная трансплантология и тканевая инженерия. – 2011. – Т. 6. – № 3. – С. 76–83. [Shvalb PG, Gavrilenko AV, Kalinin RE, et al. Efficacy and safety of application “Neovasculgen” in the complex treatment patients with chronic lower limb ischemia (Iib-III phase of clinical trials). Cellular transplantology and tissue engineering. 2011;6(3): 76-83. (In Russ.)]
  20. Шабунин А.В., Кузнецов М.Р., Матвеев Д.В., и др. Комплексная оценка эффективности генно-терапевтического лечения пациентов с хронической ишемией нижних конечностей // РМЖ. – 2019. – Т. 27. – № 2. – С. 21–25. [Shabunin AV, Kuznetsov MR, Matveev DV, et al. Comprehensive assessment of the effectiveness of gene therapy in patients with chronic ischemia of the lower limbs. RMZh. 2019;27(2):21-25. (In Russ.)]
  21. Червяков Ю.В., Староверов И.Н., Власенко О.Н., и др. Современные возможности лечения Хронических облитерирующих заболеваний артерий нижних конечностей в амбулаторных условиях // Трудный пациент. – 2017. – Т. 15. – № 3. – С. 32–37. [Chervyakov YuV, Staroverov IN, Vlasenko ON, et al. Current Treatment Options for Chronic Obliterating Diseases of Lower Limb Arteries in an Outpatient Setting. Trudnyy patsient. 2017;3(15):32-37. (In Russ.)]
  22. Деев Р.В. Генная терапия в России: три года опыта // Химия и жизнь — XXI век. – 2013. – № 12. – С. 26–29. [Deev RV. Gennaya terapiya v Rossii: tri goda opyta. Khimiya I zhizn’ XXI vek. 2013;(12):26-29. (In Russ.)]
  23. Ema.europa.eu [Internet]. Strimvelis [updated 2017 Jul; cited 2019 Sep27]. Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/strimvelis.
  24. B3cnewswire.com [Internet]. Orchard Therapeutics Announces That OTL-101 Has Received a Rare Paediatric Disease Designation [updated 2017 Jul; cited 2019 Sep27]. Available from: https://www.b3cnewswire.com/201707241613/orchard-therapeutics-announces-that-otl-101-has-received-a-rare-paediatric-disease-designation.html.
  25. Мельникова Е.В., Меркулова О. В., Чапленко А.А., и др. Мировой опыт регистрации и применения препаратов для генной терапии в клинической практике // Антибиотики и химиотерапия. – 2019. – Т. 64. – № 1–2. – С. 58–68. [Melnikova EV, Merkulova OV, Chaplenko AA, et al. International Practices of Registration and Use of Drugs for Gene Therapy in Clinical Practice. Antibiotics and chemotherapy. 2019;64(1-2):58-68. (In Russ.)] https://doi.org/10.24411/0235W2990W2019W100010.
  26. Palfi S, Gurruchaga JM, Lepetit H, et al. Long-Term Follow-Up of a Phase I/II Study of ProSavin, a Lentiviral Vector Gene Therapy for Parkinson’s Disease. Hum Gene Ther Clin Dev. 2018;29(3):148-155. https://doi.org/10.1089/humc.2018.081
  27. O’Connor DM, Boulis NM. Gene therapy for neurodegenerative diseases. Trends Mol Med. 2015;21(8):504-512. https://doi.org/10.1016/j.molmed.2015.06.001.
  28. Sinclair A, Islam S, Jones S. 171. Gene Therapy: An Overview of Approved and Pipeline Technologies. In: CADTH Issues in Emerging Health Technologies. Ottawa; 2016.
  29. Hampson G, Towse A, Pearson SD. Gene therapy: evidence, value and affordability in the US health care system. J Comp Eff Res. 2018;7(1):15-28. https://doi.org/10.2217/cer-2017-0068.
  30. Гуревич К.Г., Фесюн А.В., Свистунов О.П., и др. Скрытые вопросы Эффективности и безопасности пневмококковой вакцинации // Системный анализ и управление в биомедицинских системах. – 2013. – Т. 12. – № 1. – С. 140–144. [Gurevich KG, Fesun AD, Svistunov OP, et al. Questions of efficacy and safety of pneumococcal vaccination. System analysis and management in biomedical systems. 2013;1(12):140-144. (In Russ.)]
  31. Howe SJ, Mansour MR, Schwarzwaelder K, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118(9):3143-3150. https://doi.org/10.1172/JCI35798.
  32. Ylä-Herttuala S. The Pharmacology of Gene Therapy. Mol Ther. 2017;25(8):1731-1732. https://doi.org/10.1016/j.ymthe.2017.07.007.
  33. Ledley FD, McNamee LM, Uzdil V, Morgan IW. Why commercialization of gene therapy stalled; examining the life cycles of gene therapy technologies. Gene Ther. 2014;21(2):188-194. https://doi.org/10.1038/gt.2013.72.
  34. Fischer A. Gene Therapy: From Birth to Maturity Requires Commitment to Science and Ethics. Hum Gene Ther. 2017;28(11):958. https://doi.org/10.1089/hum.2017. 29053.afr.

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Copyright (c) 2020 Gurevich K.G., Sorokina Y.A., Urakov A.L., Gavrilova D.M., Lovtsova L.V., Zanozina O.V.

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