nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2022-6-103-109nnp-1928Research ArticleREVIEWSОБЗОРЫRecombinant botulinum toxin as a new stage in the development of botulinum toxin therapy. Possibilities and perspectives of use in neurological practiceРекомбинантные ботулотоксины как новый этап развития ботулинотерапии. Возможности и перспективы применения в неврологической практикеhttps://orcid.org/0000-0002-3422-5967ШихкеримовР. К.ShikhkerimovR. K.

Рафиз Каирович Шихкеримов

115551, Москва, Домодедовская ул., 9

Rafiz Kairovich Shikhkerimov

115551, Moscow, Domodedovskaya St., 9

rodoss72@gmail.comhttps://orcid.org/0000-0002-1004-7000ИстоминаЕ. В.IstominaE. V.

115551, Москва, Домодедовская ул., 9

115551, Moscow, Domodedovskaya St., 9

ГБУЗ «Городская поликлиника № 166 Департамента здравоохранения города Москвы»РоссияCity polyclinic № 166, Moscow Healthcare DepartmentRussian Federation202219122022146103109Copyright © Shikhkerimov R.K., Istomina E.V., 20222022Шихкеримов Р.К., Истомина Е.В.Shikhkerimov R.K., Istomina E.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/1928

Currently, eight natural serotypes of botulinum neurotoxin (BNT-A-G, -X) are known. The mechanism of action of all BNT serotypes is presynaptic blockade of SNARE transport proteins (Soluble N-ethylmaleimide-sensitive factor [NSF] Attachment Protein Receptor), as a result of which the release of acetylcholine into the synaptic cleft is disrupted and neuromuscular transmission is blocked.Each botulinum toxin serotype selectively binds to its own presynaptic membrane receptor and causes cleavage of its own SNARE protein. These differences determine the neuronal specificity and activity of botulinum toxins, which leads to their unique pharmacological properties, such as activity, duration of action, and time to onset of action.In the international clinical practice, only two BNT serotypes (A and B) are allowed to be used, however, in recent years, a large number of studies on the efficacy and safety of other BNT serotypes (E, C, F) have been carried out, and technologies for changing their natural properties have been developed.One of the indications for the use of botulinum therapy in neurology is the correction of post-stroke spasticity. Currently, BNT-A is used for this purpose, clinical improvement after its injection occurs after 2 weeks, the therapeutic effect persists for 3 months, and then the symptoms of spasticity increase again, which worsens the patient's quality of life and reduces the possibility of medical rehabilitation. The use of fast-acting recombinant botulinum toxins for this purpose could help overcome this disadvantage of BNT-A therapy.Currently the LANTIMA study, supported by IPSEN company, is going on to evaluate the safety profile and level of efficacy of modified recombinant botulinum toxin type AB in the treatment of upper limb spasticity in adults.

В настоящее время известно восемь природных серотипов ботулинического нейротоксина (БНТ-A–G, -X). Механизм действия всех серотипов БНТ заключается в пресинаптической блокаде транспортных белков SNARE (Soluble N-ethylmaleimide-sensitive factor [NSF] Attachment Protein Receptor), в результате которой нарушается выброс ацетилхолина в синаптическую щель и происходит блок нервно-мышечной передачи.Каждый серотип ботулотоксина селективно связывается со «своим» рецептором пресинаптической мембраны и вызывает расщепление «своего» SNARE-белка. Эти различия определяют нейрональную специфичность и активность ботулотоксинов, что приводит к их уникальным фармакологическим свойствам, таким как активность, продолжительность действия и время до начала действия.В мировой клинической практике разрешено применение только двух серотипов БНТ (А и В), однако в последние годы проводится большое количество исследований эффективности и безопасности применения других серотипов БНТ (E, C, F), разрабатываются технологии, позволяющие изменить их природные свойства.Одним из показаний для применения ботулинотерапии в неврологии является коррекция постинсультной спастичности. В настоящее время с этой целью применяют БНТ-А, клиническое улучшение после инъекций которого наступает через 2 нед, терапевтический эффект сохраняется в течение 3 мес, а далее симптомы спастичности вновь нарастают, что ухудшает качество жизни пациентов и снижает возможности медицинской реабилитации. Применение с этой целью быстродействующих рекомбинантных ботулотоксинов могло бы помочь преодолеть данный недостаток терапии БНТ-А.Также в настоящее время при поддержке компании IPSEN проводится исследование LANTIMA по оценке профиля безопасности и уровня эффективности применения модифицированного рекомбинантного ботулинического токсина типа АВ в лечении спастичности верхних конечностей у взрослых.

ботулинический токсинсеротипы ботулотоксинарекомбинантные ботулотоксиныботулинотерапияпостинсультная спастичностьbotulinum toxinbotulinum toxin serotypesrecombinant botulinum toxinsbotulinum therapypost-stroke spasticityСтатья спонсируется компанией «ИПСЕН».This article has been supported by IPSEN Pharma.ReferencesDressler D. Botulinum toxin drugs: brief history and outlook. J Neural Transm (Vienna). 2016 Mar;123(3):277-9. doi:10.1007/s00702-015-1478-1. Epub 2015 Nov 11.Dressler D. Botulinum toxin drugs: brief history and outlook. J Neural Transm (Vienna). 2016 Mar;123(3):277-9. doi:10.1007/s00702-015-1478-1. Epub 2015 Nov 11.Jankovic J. Botulinum toxin: State of the art. Mov Disord. 2017 Aug;32(8):1131-8. doi:10.1002/mds.27072. Epub 2017 Jun 22.Jankovic J. Botulinum toxin: State of the art. Mov Disord. 2017 Aug;32(8):1131-8. doi:10.1002/mds.27072. Epub 2017 Jun 22.Супотницкий МВ. Микроорганизмы, токсины и эпидемии. Москва: Вузовская книга; 2000. Доступно по ссылке: https://www.supotnitskiy.ru/book/book1-1-5.htm (дата обращения 10.08.2022).Supotnickij MV. Mikroorganizmy, toksiny i jepidemii [Microorganisms, toxins and epidemics]. Moscow: Vuzovskaya kniga; 2000. Available from: https://www.supotnitskiy.ru/book/book1-1-5.htm (accessed 10.08.2022) (In Russ.).Chen S. Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments. Toxins. 2012;4(10):913-39. doi:10.3390/toxins4100913Chen S. Clinical Uses of Botulinum Neurotoxins: Current Indications, Limitations and Future Developments. Toxins. 2012;4(10):913-39. doi:10.3390/toxins4100913Peck MW, Smith TJ, Anniballi F, et al. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature. Toxins (Basel). 2017;9(1):38. doi:10.3390/toxins9010038Peck MW, Smith TJ, Anniballi F, et al. Historical Perspectives and Guidelines for Botulinum Neurotoxin Subtype Nomenclature. Toxins (Basel). 2017;9(1):38. doi:10.3390/toxins9010038Masuyer G, Zhang S, Barkho S, et al. Structural characterisation of the catalytic domain of botulinum neurotoxin X-high activity and unique substrate specificity. Sci Rep. 2018 Mar 14;8(1):4518. doi:10.1038/s41598-018-22842-4Masuyer G, Zhang S, Barkho S, et al. Structural characterisation of the catalytic domain of botulinum neurotoxin X-high activity and unique substrate specificity. Sci Rep. 2018 Mar 14;8(1):4518. doi:10.1038/s41598-018-22842-4Rossetto O, Pirazzini M, Montecucco C. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat Rev Microbiol. 2014;12(8):535-49. doi:10.1038/nrmicro3295Rossetto O, Pirazzini M, Montecucco C. Botulinum neurotoxins: genetic, structural and mechanistic insights. Nat Rev Microbiol. 2014;12(8):535-49. doi:10.1038/nrmicro3295Орлова ОР. Возможности и перспективы использования ботулотоксина в клинической практике. Русский медицинский журнал. 2006;14(23):3-10. Доступно по ссылке: https://paininfo.ru/articles/rmj/788.html (дата обращения 10.08.2022).Orlova OR. Opportunities and prospects for the use of botulinum toxin in clinical practice. Russkij medicinskij zhurnal. 2006;14(23):3-10. Available from: https://paininfo.ru/articles/rmj/788.html (accessed 10.08.2022) (In Russ.).Mtui EP, Gruener G, Dockery P. Fitzgerald's Clinical Neuroanatomy and Neuroscience. Philadelphia, PA: Elsevier; 2016. P. 85-101.Mtui EP, Gruener G, Dockery P. Fitzgerald's Clinical Neuroanatomy and Neuroscience. Philadelphia, PA: Elsevier; 2016. P. 85-101.Dolly JO, Lawrence GW, Meng J, et al. Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile therapeutics. Curr Opin Pharmacol. 2009;9(3):326-35. doi:10.1016/j.coph.2009.03.004Dolly JO, Lawrence GW, Meng J, et al. Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile therapeutics. Curr Opin Pharmacol. 2009;9(3):326-35. doi:10.1016/j.coph.2009.03.004Montecucco C, Papini E, Schiavo G. Bacterial protein toxins penetrate cells via a fourstep mechanism. FEBS Lett. 1994;346(1):92-8. doi:10.1016/0014-5793(94)00449-8Montecucco C, Papini E, Schiavo G. Bacterial protein toxins penetrate cells via a fourstep mechanism. FEBS Lett. 1994;346(1):92-8. doi:10.1016/0014-5793(94)00449-8Dressler D. Pharmakologie der Botulinumtoxinmedikamente [Pharmacology of botulinum toxin drugs]. HNO. 2012 Jun;60(6):496-502 (In Germ.). doi:10.1007/s00106-012-2494-1Dressler D. Pharmakologie der Botulinumtoxinmedikamente [Pharmacology of botulinum toxin drugs]. HNO. 2012 Jun;60(6):496-502 (In Germ.). doi:10.1007/s00106-012-2494-1Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev. 2000 Apr;80(2):717-66. doi:10.1152/physrev.2000.80.2.717Schiavo G, Matteoli M, Montecucco C. Neurotoxins affecting neuroexocytosis. Physiol Rev. 2000 Apr;80(2):717-66. doi:10.1152/physrev.2000.80.2.717Binz T, Rummel A. Cell entry strategy of clostridial neurotoxins. J Neurochem. 2009 Jun;109(6):1584-95. doi:10.1111/j.1471-4159.2009.06093.x. Epub 2009 Apr 28.Binz T, Rummel A. Cell entry strategy of clostridial neurotoxins. J Neurochem. 2009 Jun;109(6):1584-95. doi:10.1111/j.1471-4159.2009.06093.x. Epub 2009 Apr 28.Dong M, Yeh F, Tepp WH, et al. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006 Apr 28;312(5773):592-6. doi:10.1126/science.1123654. Epub 2006 Mar 16.Dong M, Yeh F, Tepp WH, et al. SV2 is the protein receptor for botulinum neurotoxin A. Science. 2006 Apr 28;312(5773):592-6. doi:10.1126/science.1123654. Epub 2006 Mar 16.Pirazzini M, Rossetto O, Eleopra R, et al. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology. Pharmacol Rev. 2017;69(2):200-35. doi:10.1124/pr.116.012658Pirazzini M, Rossetto O, Eleopra R, et al. Botulinum Neurotoxins: Biology, Pharmacology, and Toxicology. Pharmacol Rev. 2017;69(2):200-35. doi:10.1124/pr.116.012658Dong M, Richards DA, Goodnough MC, et al. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J Cell Biol. 2003;162(7):1293-303. doi:10.1083/jcb.200305098Dong M, Richards DA, Goodnough MC, et al. Synaptotagmins I and II mediate entry of botulinum neurotoxin B into cells. J Cell Biol. 2003;162(7):1293-303. doi:10.1083/jcb.200305098Donald S, Elliott M, Gray B, et al. A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo. Pharmacol Res Perspect. 2018;6(6):e00446. doi:10.1002/prp2.446Donald S, Elliott M, Gray B, et al. A comparison of biological activity of commercially available purified native botulinum neurotoxin serotypes A1 to F1 in vitro, ex vivo, and in vivo. Pharmacol Res Perspect. 2018;6(6):e00446. doi:10.1002/prp2.446Tsai YC, Maditz R, Kuo CL, et al. Targeting botulinum neurotoxin persistence by the ubiquitin-proteasome system. Proc Natl Acad Sci USA. 2010;107(38):16554-9. doi:10.1073/pnas.1008302107Tsai YC, Maditz R, Kuo CL, et al. Targeting botulinum neurotoxin persistence by the ubiquitin-proteasome system. Proc Natl Acad Sci USA. 2010;107(38):16554-9. doi:10.1073/pnas.1008302107Wang J, Zurawski TH, Meng J, et al. A dileucine in the protease of botulinum toxin A underlies its long-lived neuroparalysis: transfer of longevity to a novel potential therapeutic. J Biol Chem. 2011;286(8):6375-85. doi:10.1074/jbc.m110.181784Wang J, Zurawski TH, Meng J, et al. A dileucine in the protease of botulinum toxin A underlies its long-lived neuroparalysis: transfer of longevity to a novel potential therapeutic. J Biol Chem. 2011;286(8):6375-85. doi:10.1074/jbc.m110.181784Артеменко АР, Куренков АЛ. Ботулинический токсин: вчера, сегодня, завтра. Нервно-мышечные болезни. 2013;(2):6-19. Доступно по ссылке: https://nmb.abvpress.ru/jour/article/view/44/40 (дата обращения 10.08.2022).Artemenko AR, Kurenkov AL. Botulinum toxin: yesterday, today, tomorrow. Nervnomyshechnyye bolezni = Neuromuscular Diseases. 2013;(2):6-19. Available from: https://nmb.abvpress.ru/jour/article/view/44/40 (accessed 10.08.2022) (In Russ.).Fonfria E, Maignel J, Lezmi S, et al. The Expanding Therapeutic Utility of Botulinum Neurotoxins. Toxins (Basel). 2018;10(5):208. doi:10.3390/toxins10050208Fonfria E, Maignel J, Lezmi S, et al. The Expanding Therapeutic Utility of Botulinum Neurotoxins. Toxins (Basel). 2018;10(5):208. doi:10.3390/toxins10050208Bentivoglio AR, Del Grande A, Petracca M, et al. Clinical differences between botulinum neurotoxin type A and B. Toxicon. 2015;107(Pt A):77-84. doi:10.1016/j.toxicon.2015.08.001Bentivoglio AR, Del Grande A, Petracca M, et al. Clinical differences between botulinum neurotoxin type A and B. Toxicon. 2015;107(Pt A):77-84. doi:10.1016/j.toxicon.2015.08.001Ginsberg D. The epidemiology and pathophysiology of neurogenic bladder. Am J Manag Care. 2013;19(10 Suppl):s191-6.Ginsberg D. The epidemiology and pathophysiology of neurogenic bladder. Am J Manag Care. 2013;19(10 Suppl):s191-6.Королев АА. К вопросу о ботулинотерапии постинсультного спастического пареза: механизмы действия ботулотоксина, алгоритм восстановительного лечения. Лечащий врач. 2012;(2):78-84. Доступно по ссылке: https://www.lvrach.ru/2012/02/15435355 (дата обращения 10.08.2022).Korolev AA. On the issue of botulinum therapy for post-stroke spastic paresis: mechanisms of action of botulinum toxin, algorithm for restorative treatment. Lechashhij vrach. 2012;(2):78-84. Available from: https://www.lvrach.ru/2012/02/15435355 (accessed 10.08.2022) (In Russ.).Spasticity in adults: management using botulinum toxin. National guidelines. London: RCP; 2018. Available from: https://www.kcl.ac.uk/cicelysaunders/attachments/spasticity-in-adults-managment-usingbotulinum-toxin.pdfSpasticity in adults: management using botulinum toxin. National guidelines. London: RCP; 2018. Available from: https://www.kcl.ac.uk/cicelysaunders/attachments/spasticity-in-adults-managment-usingbotulinum-toxin.pdfИшемический инсульт и транзиторная ишемическая атака у взрослых. Клинические рекомендации. Москва: Минздрав России; 2021. Доступно по ссылке: https://cr.minzdrav.gov.ru/schema/171_2 (дата обращения 10.08.2022).Ischemic stroke and transient ischemic attack in adults. Clinical guidelines. Moscow: Ministry of Health of Russia; 2021. Available from: https://cr.minzdrav.gov.ru/schema/171_2 (accessed 10.08.2022) (In Russ.).Datta Gupta A, Visvanathan R, Cameron I, et al. Efficacy of botulinum toxin in modifying spasticity to improve walking and quality of life in post-stroke lower limb spasticity – a randomized double-blind placebo controlled study. BMC Neurol. 2019;19(1):96. doi:10.1186/s12883-019-1325-3Datta Gupta A, Visvanathan R, Cameron I, et al. Efficacy of botulinum toxin in modifying spasticity to improve walking and quality of life in post-stroke lower limb spasticity – a randomized double-blind placebo controlled study. BMC Neurol. 2019;19(1):96. doi:10.1186/s12883-019-1325-3Eleopra R, Rinaldo S, Montecucco C, et al. Clinical duration of action of different botulinum toxin types in humans. Toxicon. 2020;179:84-91. doi:10.1016/j.toxicon.2020.02.020Eleopra R, Rinaldo S, Montecucco C, et al. Clinical duration of action of different botulinum toxin types in humans. Toxicon. 2020;179:84-91. doi:10.1016/j.toxicon.2020.02.020Yoelin SG, Dhawan SS, Vitarella D, et al. Safety and Efficacy of EB-001, a Novel Type E Botulinum Toxin, in Subjects with Glabellar Frown Lines: Results of a Phase 2, Randomized, Placebo-Controlled, AscendingDose Study. Plast Reconstr Surg. 2018;142(6):847e-855e. doi:10.1097/PRS.0000000000005029Yoelin SG, Dhawan SS, Vitarella D, et al. Safety and Efficacy of EB-001, a Novel Type E Botulinum Toxin, in Subjects with Glabellar Frown Lines: Results of a Phase 2, Randomized, Placebo-Controlled, AscendingDose Study. Plast Reconstr Surg. 2018;142(6):847e-855e. doi:10.1097/PRS.0000000000005029Webb RP. Engineering of Botulinum Neurotoxins for Biomedical Applications. Toxins (Basel). 2018;10(6):231. doi:10.3390/toxins10060231Webb RP. Engineering of Botulinum Neurotoxins for Biomedical Applications. Toxins (Basel). 2018;10(6):231. doi:10.3390/toxins10060231Tao L, Peng L, Berntsson RP, et al. Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors. Nat Commun. 2017;8(1):53. doi:10.1038/s41467-017-00064-yTao L, Peng L, Berntsson RP, et al. Engineered botulinum neurotoxin B with improved efficacy for targeting human receptors. Nat Commun. 2017;8(1):53. doi:10.1038/s41467-017-00064-yRaphael BH, Choudoir MJ, Luquez C, et al. Sequence diversity of genes encoding botulinum neurotoxin type F. Appl Environ Microbiol. 2010;76(14):4805-12. doi:10.1128/aem.03109-09Raphael BH, Choudoir MJ, Luquez C, et al. Sequence diversity of genes encoding botulinum neurotoxin type F. Appl Environ Microbiol. 2010;76(14):4805-12. doi:10.1128/aem.03109-09Burgin D, Perier C, Hackett G, et al. New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency. Toxins (Basel). 2021;13(12):834. doi:10.3390/toxins13120834Burgin D, Perier C, Hackett G, et al. New Modified Recombinant Botulinum Neurotoxin Type F with Enhanced Potency. Toxins (Basel). 2021;13(12):834. doi:10.3390/toxins13120834Weisemann J, Krez N, Fiebig U, et al. Generation and Characterization of Six Recombinant Botulinum Neurotoxins as Reference Material to Serve in an International Proficiency Test. Toxins (Basel). 2015;7(12):5035-54. doi:10.3390/toxins7124861Weisemann J, Krez N, Fiebig U, et al. Generation and Characterization of Six Recombinant Botulinum Neurotoxins as Reference Material to Serve in an International Proficiency Test. Toxins (Basel). 2015;7(12):5035-54. doi:10.3390/toxins7124861Rasetti-Escargueil C, Popoff MR. Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development. Toxins (Basel). 2020 Dec 22;13(1):1. doi:10.3390/toxins13010001Rasetti-Escargueil C, Popoff MR. Engineering Botulinum Neurotoxins for Enhanced Therapeutic Applications and Vaccine Development. Toxins (Basel). 2020 Dec 22;13(1):1. doi:10.3390/toxins13010001Fonfria E, Elliott M, Beard M, et al. Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity. Toxins (Basel). 2018 Jul 4;10(7):278. doi:10.3390/toxins10070278Fonfria E, Elliott M, Beard M, et al. Engineering Botulinum Toxins to Improve and Expand Targeting and SNARE Cleavage Activity. Toxins (Basel). 2018 Jul 4;10(7):278. doi:10.3390/toxins10070278Hooker A, Palan S, Beard M. Recombinant botulinum neurotoxin serotype A1 (SXN102342): Protein engineering and process development. Toxicon. 2016;123:40. doi:10.1016/j.toxicon.2016.11.113Hooker A, Palan S, Beard M. Recombinant botulinum neurotoxin serotype A1 (SXN102342): Protein engineering and process development. Toxicon. 2016;123:40. doi:10.1016/j.toxicon.2016.11.113Perier C, Martin V, Cornet S, et al. Recombinant botulinum neurotoxin serotype A1 in vivo characterization. Pharmacol Res Perspect. 2021;9(5):e00857. doi:10.1002/prp2.857Perier C, Martin V, Cornet S, et al. Recombinant botulinum neurotoxin serotype A1 in vivo characterization. Pharmacol Res Perspect. 2021;9(5):e00857. doi:10.1002/prp2.857Keith F, John C. Targeted secretion inhibitors-innovative protein therapeutics. Toxins (Basel). 2010 Dec;2(12):2795-815. doi:10.3390/toxins2122795. Epub 2010 Dec 3.Keith F, John C. Targeted secretion inhibitors-innovative protein therapeutics. Toxins (Basel). 2010 Dec;2(12):2795-815. doi:10.3390/toxins2122795. Epub 2010 Dec 3.Pons L, Vilain C, Volteau M, et al. Safety and pharmacodynamics of a novel recombinant botulinum toxin E (rBoNT-E): Results of a phase 1 study in healthy male subjects compared with abobotulinumtoxinA (Dysport®). J Neurol Sci. 2019;407:116516. doi:10.1016/j.jns.2019.116516Pons L, Vilain C, Volteau M, et al. Safety and pharmacodynamics of a novel recombinant botulinum toxin E (rBoNT-E): Results of a phase 1 study in healthy male subjects compared with abobotulinumtoxinA (Dysport®). J Neurol Sci. 2019;407:116516. doi:10.1016/j.jns.2019.116516Eleopra R, Tugnoli V, Rossetto O, et al. Different time courses of recovery after poisoning with botulinum neurotoxin serotypes A and E in humans. Neurosci Lett. 1998 Nov 13;256(3):135-8. doi:10.1016/s0304-3940(98)00775-7Eleopra R, Tugnoli V, Rossetto O, et al. Different time courses of recovery after poisoning with botulinum neurotoxin serotypes A and E in humans. Neurosci Lett. 1998 Nov 13;256(3):135-8. doi:10.1016/s0304-3940(98)00775-7Jacinto J, Varriale P, Pain E, et al. Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity. Front Neurol. 2020 May 7;11:388. doi:10.3389/fneur.2020.00388. Erratum in: Front Neurol. 2020 Dec 17;11:629181.Jacinto J, Varriale P, Pain E, et al. Patient Perspectives on the Therapeutic Profile of Botulinum Neurotoxin Type A in Spasticity. Front Neurol. 2020 May 7;11:388. doi:10.3389/fneur.2020.00388. Erratum in: Front Neurol. 2020 Dec 17;11:629181.A Study to Assess the Safety and Efficacy of IPN10200 of in Adult Participants with Upper Limb Spasticity (LANTIMA). Available from: https://clinicaltrials.govA Study to Assess the Safety and Efficacy of IPN10200 of in Adult Participants with Upper Limb Spasticity (LANTIMA). Available from: https://clinicaltrials.gov

The authors declare that there are no conflicts of interest present.