AL THERAPY DEVELOPMENT: CHALLENGES AND OPPORTUNITIES
Autor: Antonio Jorge de Melo | Publicado: 2016-08-13T07:22:00-07:00

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&nbsp; 







Michael Benatar Neurology, University of
Miami, Miami, FL, US

STEM CELL THERAPY IN
ALS



Jonathan D. Glass1 ,
Nicholas M. Boulis1 , Parag G. Patil2 , Nazem Atassi3 , Merit Cudkowicz4 , Karl
Johe5 , Stephen A. Goutman2 , Eva L. Feldman6 1 Emory University, Atlanta, GA,
US;2 University of Michigan, Ann Arbor, MI, US;3 Massachusetts General
Hospital, Boston, MA, US;4 Neurology, MGH, Boston, MA, US;5 Neuralstem, Inc.,
Germantown, MD, US;6 Department Of Neurology, University of Michigan, Ann
Arbor, MI, US that correlate with
ALSFRS-R scores were examined to inform future trial phase endpoints, and the
Phase 2a trial was expanded to include 3 surgical centers, supporting the
feasibility of future largerscale trials. Overall, our progress to date
supports continued examination of this therapeutic strategy, and future trial
phases assessing effi cacy are being planned.






As terapias celulares
oferecem múltiplos benefícios para combater a complexa gênese da esclerose
lateral amiotrófica (ELA), uma doença fatal caracterizada pela progressiva
degeneração dos neurônios motores. Enquanto vários tipos de célula e diferentes
formas de entrega farmacológiatêm sido examinados, a nossa experiência no
desenvolvimento de uma estratégia de transplante intra espinal empregando
células-tronco humanas (HSSC, da sigla em ingles para human spinal stem cells) nos conduziu a dois ensaios clínicos pela
primeira vez testados em humanos e aprovados pelo FDA.&nbsp;



O ensaio de Fase 1
seguiu um planejamento com escalonamento de risco em que 15 pacientes com ELA
foram submetidos a um risco aumentado por 5 com basenos seus níveis de
deficiência no momento da cirurgia e no número e atribuição de injeções. Doses
finais variaram de 500000 a 1 milhão de células e foram aplicadas em 5 ou 10
injeções unilaterais ou bilaterais, objetivando atingir amedula espinhal lombar
e/ou cervical. Os resultados demonstraram que a estratégia de transplante intra
espinhal de células tronco foi segura, viável e bem tolerada, e o monitoramento
da evolução clínica ainda revelou uma visão preliminar sobre os potenciais de atividade
biológica da células-tronco. No ensaio de Fase 2a subsequente, a segurança das
doses crescentes de células estaminais com variações de 2 a 16 milhões de
células, níveisestes obtidos através de um aumento das concentrações por injeção
e do número de injeções, foi avaliada.



A análise dos resultados estão em curso
e serão apresentados, no entanto, a abordagem aplicada foi bem tolerada em
todos os grupos, incluindo o grupo que recebeu 8 milhões de células em mais de
20 injeções e em ambas as regiões da medula espinhal cervical e lombar. Comparação
entre as medições dos resultados funcionais dos pacientes após o procedimento
com grupos de controle históricos também revelou que a terapia não acelera a
progressão da doença, adicionalmente verificando a segurança, comjanelas potenciais
de atividade biológica que foram novamente observadas. Além disso, a observação
dos potenciais resultados e medições que se correlacionam com os valores da
escala de avaliação clínica e funcional do comprometimento respiratório (ALSFRS-R)
foram examinados para informar futuros pontos finais da fase de testes, e o
ensaio de Fase 2a foi expandido para incluir 3 centros cirúrgicos, dando apoio
a viabilidade de futuros ensaios em grande escala.



No geral, o nosso progresso
até o momento suporta o exame continuado dessa estratégia terapêutica, e
futuras fases de ensaios que avaliam a eficácia estão sendo planejadas.






Tradução do abstract:&nbsp;STEM CELL THERAPY IN ALS

Natasha Marzliak