{"id":7152,"date":"2009-04-24T03:18:18","date_gmt":"2009-04-24T03:18:18","guid":{"rendered":"http:\/\/agenciainclusive.wordpress.com\/?p=7152"},"modified":"2009-04-24T03:18:18","modified_gmt":"2009-04-24T03:18:18","slug":"under-the-microscope-a-pharmacotherapy-for-down-syndrome","status":"publish","type":"post","link":"https:\/\/inclusivenews.com.br\/?p=7152","title":{"rendered":"Sob o microsc\u00f3pio – Uma Farmacoterapia para a S\u00edndrome de Down?"},"content":{"rendered":"

Por Dr Alberto Costa<\/p>\n

Tradu\u00e7\u00e3o: Frederico Pereira<\/p>\n

Como muitos leitores da Down\u00b4s Update s\u00e3o pais de crian\u00e7as muito novas e podem
\nn\u00e3o ter ouvido falar da minha pesquisa ou de mim, uma reintrodu\u00e7\u00e3o faz-se
\nnecess\u00e1ria. Meu nome \u00e9 Alberto Costa e eu desempenho muitos papeis. Eu sou
\ndoutor em medicina e um cientista do c\u00e9rebro que tem dedicado os \u00faltimos 12 anos
\nexclusivamente ao estudo da SD. Eu sou professor associado de Medicina e
\nNeuroci\u00eancias na Univerdade do Colorado em Denver. E eu tamb\u00e9m sou um orgulhoso
\npai de uma crian\u00e7a com S\u00edndrome de Down chamada Tyche.<\/p>\n

Treze anos atr\u00e1s, Tyche nasceu em Houston, Texas, com um estreitamento anormal
\nda primeria parte do intestino delgado, conhecido como estenosis duodenal, que
\nprecisou ser corrigido cirurgicamente justamente quando ela celebrava o primeiro
\nm\u00eas de vida. Esta foi a primeira de muitas viagens ao hospital que eu e minha
\nesposa tivemos que vivenciar no par de anos subsequentes. Atualmente, Tyche
\n\u00e9, em geral, saud\u00e1vel. Por\u00e9m, este estado algumas vezes camufla uma grave
\nalergia alimentar escondida, que, no caso de Tyche, pode levar a uma anaphilaxia
\nse ela beber um pouco de leite ou comer um ovo cozido. Tyche est\u00e1 no ensino
\nm\u00e9dio, num ambiente de educa\u00e7\u00e3o inclusiva. Mesmo sabendo que ela luta com a
\nmaioria dos assuntos da s\u00e9tima s\u00e9rie, ela possui uma misteriosa habilidade para
\nsoletrar (mesmo quando comparada com seus colegas) e est\u00e1 come\u00e7ando a mostrar um
\nprogressivo dom\u00ednio de conceitos de matem\u00e1tica e gram\u00e1tica (que, em geral, est\u00e3o
\nnum n\u00edvel de quinta s\u00e9rie).<\/p>\n

Apenas alguns meses ap\u00f3s o anivers\u00e1rio de Tyche, eu fui impulsionado por uma
\nesperan\u00e7a de que o d\u00e9ficit cognitivo associado com a sua desordem gen\u00e9tica
\npudesse ser amenizado por um ou mais medicamentos conhecidos por afetarem o
\nfuncionamento do c\u00e9rebro. Isto foi o come\u00e7o de uma jornada pessoal e
\nprofissional de 12 anos em busca de uma f\u00e1rmaco-terapia projetada para melhorar
\na qualidade de vidas das pessoas com s\u00edndrome de Down.<\/p>\n

Na \u00e9poca em que minha filha nasceu, eu estava terminando minhas pesquisas de
\np\u00f3s-gradua\u00e7\u00e3o no Baylor College de Medicina.<\/p>\n

Mesmo sabendo da minha paix\u00e3o pela ci\u00eancia desde os meus 8 anos, eu tenho que
\ncofessar que, naqueles dias, eu estava me tornando progressivamente mais
\naborrecido com a pr\u00e1tica da ci\u00eancia. Como o exemplo da minha experi\u00eancia pessoal
\ndos efeitos transformadores que o nascimento de uma crian\u00e7a com s\u00edndrome de Down
\nprovoca na vida de qualquer um, eu posso atestar que o nascimento de Tyche
\nreacendeu e focou novamente minha paix\u00e3o pelo desafio da ci\u00eancia. N\u00f3s nos
\nmudados do Texas e fomos para o Maine, onde eu me juntei \u00e0 faculdade do
\nLaborat\u00f3rio Jackson, uma extraordin\u00e1ria equipe cient\u00edfica dedicada a criar e
\nestudar cobaias (ratinhos) que desenvolvem doen\u00e7as humanas. Apenas alguns anos
\nantes de nos mudarmos, uma cientista Senior daquela institui\u00e7\u00e3o, Dr. Muriel
\nDavisson, tinha criado a cobaia de laboratorio Ts65Dn, o primeiro modelo de rato
\nde laborat\u00f3rio com s\u00edndrome de Down que tinha um cromossomo extra e vivia at\u00e9 a
\nidade adulta.<\/p>\n

A cobaia Ts65Dn ensinou-nos muito sobre a biologia da s\u00edndrome de Down. Estes
\nratos exibem muitas das caracter\u00edsticas que se assemelham \u00e0quelas vistas em
\npessoas com s\u00edndrome de Down. Ainda mais importante, estes animais nos mostraram
\no fato que a s\u00edndomre de Down est\u00e1 associada a diversas disfun\u00e7\u00f5es da estrutura
\ncerebral chamada hippocampo. O hippocampo \u00e9 conhecido pela sua
\nimport\u00e2ncia na forma\u00e7\u00e3o e reten\u00e7\u00e3o de novas mem\u00f3rias e \u00e9 uma das primeiras
\nregi\u00f5es do c\u00e9rebro a sofrer danos com a doen\u00e7a de Alzheimer. Trabalhos feitos na
\nUniversidade de Denver pele doutores Bruce Pennington, Jennifer Moon e Lynn
\nNadel confirmaram que a fun\u00e7\u00e3o do hippocampo \u00e9 desproporcionalmente afetada em
\npessoas com s\u00edndrome de Down. Eu fa\u00e7o pesquisas com a cobaia Ts65Dn e outros
\ntipos de cobaias que possuem s\u00edndrome de Down h\u00e1 mais de doze anos.<\/p>\n

Meus conhecimentos pr\u00e9vios como m\u00e9dico-cientista t\u00eam permitido, adicionalmente,
\nque eu conduza diversas avalia\u00e7\u00f5es neurofisiol\u00f3gicas em indiv\u00edduos com s\u00edndrome
\nde Down na grande Denver. Eu tamb\u00e9m sou privilegiado por observar a evolu\u00e7\u00e3o
\ngeral das pesquisas em s\u00edndrome de Down internamente, participando em projetos
\ncolaborativos no Jackson Laboratory, na Univerdidade Hopkins e no Instituto
\nEleanor Roosevelt. Durante este tempo, tornou-se claro para mim que a gen\u00e9tica
\npode ir tmuito longe no alcance de uma op\u00e7\u00e3o de tratamento para os problemas
\nassociados com a s\u00edndrome de Down. Como resultado, meu laborat\u00f3rio investiu a
\nmaioria das suas energias no teste de terapias potenciais endere\u00e7adas a atingir
\nos d\u00e9ficites cognitivos em cobaias. De fato, eu fui a primeira pessoas a receber
\num grande financiamento do Instituto Nacional da Sa\u00fade (NIH) para estudar
\nexclusivamente o potencial de f\u00e1rmaco-terapias para s\u00edndrome de Down. Durante os
\ncinco anos de pesquisa cobertos por este financiamento e pelos tr\u00eas anos
\nsubsequentes, eu testei d\u00fazias de diferentes componentes de a\u00e7\u00e3o cerebral na
\ncobaia Ts65Dn.<\/p>\n

Recentemente, nossa pesquisa apontou a \u00fanica efic\u00e1cia de uma droga chamada
\nmemantine hydrochloride (memantime) na melhoria dos d\u00e9ficits de aprendizagem e
\nda memoriza\u00e7\u00e3o das cobaias Ts65Dn (recentemente publicado no jornal de
\nNeusofisiofarmacologia). Memantine \u00e9 uma droga aprovada pela FDA para pacientes
\ncom dem\u00eancia-Alzheimer de moderada a severa. Recentes estudos cl\u00ednicos sugerem
\nque a memantine tamb\u00e9m poder\u00e1 ser clinicamente \u00fatil e bem tolerada em indiv\u00edduos
\njovens com outras condi\u00e7\u00f5es que produzam defici\u00eancias cognitivas, tais como
\nautismo e desordem por d\u00e9ficit de aten\u00e7\u00e3o e hiperatividade (ADHD, no ingl\u00eas).<\/p>\n

Para por em campo nossos empolgante achados pr\u00e9-cl\u00ednicos, reuni um ensaio
\ncl\u00ednico piloto para estudar a tolerabilidade e efic\u00e1cia da memantina em adultos
\njovens com s\u00edndrome de Down. Sou privilegiado por poder conduzir um
\nimpressionante grupo de m\u00e9dicos e psic\u00f3logos neste esfor\u00e7o. Dr. Pennington tem
\nsido importante na ajuda de projetar o ensaio e seu ex-aluno, o Dr. Richard
\nBoada, ser\u00e1 o respons\u00e1vel pela aplica\u00e7\u00e3o dos testes psicol\u00f3gicos associados com
\no experimento. Nosso protocolo de investiga\u00e7\u00e3o foi financiado pela Forest
\nPharmaceuticals e recebeu revis\u00e3o institucional pela Colorado Multiple
\nInstitutional Review Board (COMIRB). Come\u00e7amos a contrata\u00e7\u00e3o para este estudo
\nmuito recentemente, e do ensaio cl\u00ednico est\u00e1 a ter lugar no Universidade do
\nColorado e The Children’s Hospital, no Anschutz
\nMedicina Campus em Aurora.<\/p>\n

O objetivo do nosso estudo cl\u00ednico piloto \u00e9 determinar se a memantina tem o
\npotencial para ajudar a melhorar a mem\u00f3ria e outras habilidades cognitivas dos
\njovens adultos com s\u00edndrome de Down ao longo de uma tratamento de 16-semanas.
\nQuarenta pessoas
\ncom s\u00edndrome de Down de ambos os sexos, com idades compreendidas entre os 18-32
\nanos, ir\u00e3o participar neste estudo. Este \u00e9 um estudo aleat\u00f3rio duplo-cego
\nplacebo-controlado, o que significa que cada participante ter\u00e1 uma chance de
\n50\/50 de receber a memantina ou p\u00edlulas placebo (p\u00edlula inativa). Al\u00e9m disso,
\nnem os participantes estudados nem os pesquisadores vai saber quem est\u00e1
\nrecebendo medica\u00e7\u00e3o ativa ou placebo at\u00e9 ao final do estudo. Com base no modo de
\na\u00e7\u00e3o da memantina e conhecimentos atuais sobre a fun\u00e7\u00e3o cerebral
\nem pessoas com s\u00edndrome de Down, nossa hip\u00f3tese \u00e9 que a memantina pode melhorar
\na pontua\u00e7\u00e3o nos testes de adultos jovens com S\u00edndrome de Down em testes de mem\u00f3ria voltados para a fun\u00e7\u00e3o da estrutura do c\u00e9rebro chamada de hippocampo.Este projeto de pesquisa tamb\u00e9m foi concebido
\npara explorar se a memantina \u00e9 bem tolerada pelos participantes do estudo.<\/p>\n

Existe tamb\u00e9m uma pequena mas realista possibilidade que a memantina possa
\nefetivamente retardar o aparecimento da doen\u00e7a de Alzheimer em jovens adultos
\ncom s\u00edndrome de Down. Mas o nosso estudo n\u00e3o foi planejado para testar esta
\nhip\u00f3tese. Dependendo dos resultados do nosso estudo, esperamos expandir a
\ndimens\u00e3o e o alcance das nossas investiga\u00e7\u00f5es e obter um experimento mais longo
\ne multic\u00eantrico da memantine em pessoas com s\u00edndrome de Down. Estamos tamb\u00e9m
\nplanejando o envolvimento de pessoas mais jovens nos experimentos futuros.<\/p>\n

Se voc\u00ea desejar aprender mais ou participar deste experimento cl\u00ednico, pode me
\ncontactar pelo email Alberto.Costa@uchsc.edu<\/a>.<\/p>\n

\u00c9 importante destacar que a minha investiga\u00e7\u00e3o n\u00e3o teria sido poss\u00edvel sem os
\nfinanciamentos em diferentes est\u00e1gios da National Down Syndrome Society, da Funda\u00e7\u00e3o Enoch-Gelbard , do National Institute for Child Health and Development, Anna & John Sie Foundation, do Coleman Institute for Cognitive Disabilities, da Jerome Lejeune Foundation, da Lowe Fund of the Denver Foundation, da Lutheran Good Samaritan, da Colorado Springs Down Syndrome Association, e da Mile High Down Syndrome Association.. Embora isto possa ser uma lista impressionante, isso n\u00e3o elimina o fato de que, como j\u00e1 disse v\u00e1rias vezes (veja, por exemplo,
\nhttp:\/\/www.mhdsa.org\/ResearchCosta.htm<\/a>), o financiamento para investiga\u00e7\u00e3o da S\u00edndrome de Down \u00e9 ainda muito pequeno quando comparado a outros dist\u00farbios associados com a defici\u00eancia , como o Autismo
\ne o Fragile-X. Por favor, considere a possibilidade de enviar uma doa\u00e7\u00e3o ou voluntariar o seu tempo para a S\u00edndrome de Down Research Fund Raising Group (DSR | FRG), c\/o Mile High Down Syndrome Association, 2121 S. Oneida St, Suite 600, Denver, CO 80224.<\/p>\n

Under the Microscope – A Pharmacotherapy for Down Syndrome ?<\/p>\n

By Alberto Costa, M.D., Ph.D.<\/p>\n

Because many readers of Down\u2019s Update are parents of very young children who may not have heard of my research or me, I figured that a reintroduction was in order. My name is Alberto Costa, and I wear many hats. I am a medical doctor and a brain scientist who has dedicated the last 12 years exclusively to the study of Down syndrome. I am an Associate Professor of Medicine and Neuroscience at the University of Colorado Denver. And I am also the proud parent of a child with Down syndrome named Tyche. Thirteen years ago, Tyche was born in Houston, Texas, with an
\nabnormal narrowing of the fi rst portion of her small intestine, known as duodenal stenosis, which needed to be corrected surgically just as we celebrated her fi rst month of life. This was to be the fi rst of many trips to the hospital that my wife and I had to take over the subsequent couple of years. Nowadays, Tyche is generally healthy. But this state of affairs sometimes disguises an underlying severe food allergy, which in Tyche\u2019s case can lead to anaphylaxis if she drinks as little as half an ounce of milk or eats a bite from a boiled egg. Tyche attends middle school in a mostly inclusive setting. Even though she struggles with most of the seventh-grade material, she has an uncanny spelling ability (even when compared to her typical peers) and is starting to show progressively improved grasp of math and grammar concepts (which, overall, are at the fi fth grade level).
\nJust a few months after Tyche\u2019s birth, I became driven by an \u201cinformed hope\u201d that the cognitive defi cits associated with her genetic disorder could be ameliorated by one or more medications known to affect the function of the brain. This was the beginning of a twelve-year professional and personal journey in search of a pharmacotherapy designed to improve the quality of life of persons with Down syndrome. At the time my daughter was born, I was fi nishing my
\npostgraduate research training at Baylor College of Medicine. Even though I could trace my passion for scientific matters from when I was eight years old, I have to confess that, in those days, I was becoming progressively more jaded with the praxis of science. As an example of my own personal experience on the transformative effects that the birth of a child with Down syndrome can have on one\u2019s life, I can attest that Tyche\u2019s birth rekindled and refocused my passion for the scientific enterprise. We uprooted from Texas and went to Maine where I joined the faculty of The Jackson Laboratory, an amazing scientific facility dedicated to creating and studying mouse models of human
\ndiseases and disorders. Just a few years before we moved, a Senior Staff Scientist of that institution, Dr. Muriel Davisson, had created the Ts65Dn mouse, the fi rst mouse model for Down syndrome that had an extra chromosome and that lived to adulthood.
\nThe Ts65Dn mouse has taught us a lot about the biology of Down syndrome. These mice display many features that
\nresemble those seen in persons with Down syndrome. But, perhaps more importantly, these animals have hinted to the fact that Down syndrome is associated with severe dysfunction of the brain structure called the hippocampus. The hippocampus is thought to be important for the formation or retention of new memories and is one of the fi rst regions of the brain to suffer damage in Alzheimer\u2019s disease. Work done at the University of Denver by Drs. Bruce Pennington, Jennifer Moon, and Lynn Nadel indeed confi rmed that the function of the hippocampus is disproportionably affected in persons with Down syndrome. I have been doing research with Ts65Dn mice and other mouse models of Down syndrome for over twelve years now. My background as a physician-scientist has, additionally, allowed me to conduct various neurophysiological assessments in individuals with Down syndrome in the greater Denver area. I also have been privileged to observe the general evolution of the Down syndrome research fi eld from the inside by participating in collaborative program projects at The Jackson Laboratory, Johns Hopkins University, and the Eleanor Roosevelt Institute. During this time, it became clear to me that genetics would only
\ngo so far towards addressing treatment options for the cognitive impairments associated with Down syndrome. As a result, my lab has invested most of its energies in testing potential therapies that might address such cognitive defi cits in mouse models. In fact, I was the fi rst person awarded a major grant from the National Institutes of Health (NIH) to exclusively study potential pharmacotherapies for Down syndrome. During the five years covered by that research grant and the three subsequent years, I have tested a dozen different brain-acting compounds on Ts65Dn mice.
\nRecently, our research has pinpointed the unique efficacy of a drug called memantine hydrochloride (memantine) in ameliorating learning and memory defi cits of the Ts65Dn mouse (recently published in the journal neuropsycopharmacology). Memantine is a drug approved by the Food and Drug Administration (FDA)
\nfor patients with moderate to severe Alzheimer-type dementia. Recent clinical studies suggest that memantine also may be clinically useful and well tolerated in young individuals with other conditions that produce cognitive disabilities, such as autism and attention defi cit hyperactivity disorder (ADHD).
\nIn order to build off of our exciting preclinical fi ndings, I put together a pilot clinical trial to study the tolerability and efficacy of memantine in young adults with Down syndrome. I am fortunate to lead an impressive group of physicians and psychologists in this endeavor. Dr. Pennington has been instrumental in helping with the design of the trial and his former graduate student, Dr. Richard Boada, will be the neuropsychologist responsible for applying the psychological tests associated with the trial. Our research protocol has been funded as an investigator-initiated
\ngrant by Forest Pharmaceuticals and has received institutional review board approval from the Colorado Multiple Institutional Review Board (COMIRB). We have started recruitment for this study very recently, and the clinical trial is taking place at the University of Colorado and The Children\u2019s Hospital at the Anschutz Medical Campus in Aurora. cognitive abilities of young adults with Down syndrome over the course of a 16-week treatment. Forty persons
\nwith Down syndrome of both genders, aged 18-32 years, will take part in this study. This is a randomized double-
\nblind placebo-controlled study, which means that each participant will have a 50\/50 chance of being assigned
\nto receive either the memantine pills or placebo (inactive mode of action and current knowledge on brain function
\nin persons with Down syndrome, our hypothesis is that study participants.<\/p>\n

There is also a small but realistic possibility that memantine may indeed delay the onset of Alzheimer-type disease in young adults with Down syndrome. But our present study was not designed to test this hypothesis. Depending on the results of our study, we hope to expand the size and scope of our investigations and pursue a longer, multicenter, trial on memantine in persons with Down syndrome. We also plan a study involving younger participants for the future.
\nIf you want to learn more or participate in this clinical trial, you can contact me at Alberto.Costa@uchsc.edu. It is important to notice that my research would not have been possible without funding at various stages from the National Down Syndrome Society, the Enoch-Gelbard Foundation, the National Institute for Child Health and Development, the Anna & John Sie Foundation, the Coleman Institute for Cognitive Disabilities, the Jerome Lejeune Foundation, the Lowe Fund of the Denver Foundation, Lutheran Good Samaritan, Colorado Springs Down Syndrome Association, and Mile High Down Syndrome Association. Even though this may be an impressive list, this does
\nnot erase the fact that, as I have mentioned many times (check, for example, http:\/\/www.mhdsa.org\/ResearchCosta.htm), funding for Down syndrome research is still very small compared to other
\ndisorders associated with intellectual disabilities, such as Autism and Fragile X. Please consider sending a donation or volunteering your time to the Down Syndrome Research Fund Raising Group
\n(DSR|FRG), c\/o Mile High Down Syndrome Association, 2121 S. Oneida St, Suite 600, Denver, CO 80224. The purpose of our pilot clinical trial is to determine whether memantine has the potential to help improve memory and other
\npills). Also, neither the study participants nor the research personnel will know who is receiving active medication or
\nplacebo until the end of the study. Based on memantine\u2019s memantine may improve test scores of young adults with Down syndrome on memory tests targeted at the function of the brain structure called the hippocampus. This research project was also designed to explore whether memantine is well tolerated by the<\/p>\n

Source: http:\/\/www.mhdsa.org\/Newsletter\/MHDSA_News_Oct-Nov08.pdf<\/p>\n","protected":false},"excerpt":{"rendered":"

Por Dr Alberto Costa Tradu\u00e7\u00e3o: Frederico Pereira Como muitos leitores da Down\u00b4s Update s\u00e3o pais de crian\u00e7as muito novas e podem n\u00e3o ter ouvido falar da minha pesquisa ou de mim, uma reintrodu\u00e7\u00e3o faz-se necess\u00e1ria. Meu nome \u00e9 Alberto Costa e eu desempenho muitos papeis. Eu sou doutor em medicina e um cientista do c\u00e9rebro […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"site-container-style":"default","site-container-layout":"default","site-sidebar-layout":"default","disable-article-header":"default","disable-site-header":"default","disable-site-footer":"default","disable-content-area-spacing":"default","footnotes":""},"categories":[8,9],"tags":[],"class_list":["post-7152","post","type-post","status-publish","format-standard","hentry","category-textos-e-artigos","category-traducoes"],"yoast_head":"\nSob o microsc\u00f3pio - Uma Farmacoterapia para a S\u00edndrome de Down? -<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/inclusivenews.com.br\/?p=7152\" \/>\n<meta property=\"og:locale\" content=\"pt_PT\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Sob o microsc\u00f3pio - Uma Farmacoterapia para a S\u00edndrome de Down? -\" \/>\n<meta property=\"og:description\" content=\"Por Dr Alberto Costa Tradu\u00e7\u00e3o: Frederico Pereira Como muitos leitores da Down\u00b4s Update s\u00e3o pais de crian\u00e7as muito novas e podem n\u00e3o ter ouvido falar da minha pesquisa ou de mim, uma reintrodu\u00e7\u00e3o faz-se necess\u00e1ria. 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Meu nome \u00e9 Alberto Costa e eu desempenho muitos papeis. 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