Aniversário
Nove anos atrás, eu estava participando de um pequeno grupo de
discussão on-line, numa época em que os blogs e as mídias sociais ainda
não eram tão populares como agora, e publiquei um pequeno resumo do que
eu estava lendo sobre a acondroplasia. Naquela
época, tendo já conversado com vários investigadores no campo e com
alguns representantes de associações de pais e pacientes, percebi que a informação
técnica e os avanços que eu via na literatura não eram fáceis de serem alcançados pela comunidade interessada. Nesse pequeno artigo, meu foco era a perspectiva futura e não reproduzir revisões que os especialistas já estavam fazendo tão bem. Reuni todas as estratégias potenciais que eu encontrei na literatura
que poderiam ser usadas para tratar a acondroplasia em alguns
parágrafos.
Como
a maioria dos participantes daquele grupo de discussão não tinha formação médica ou científica, tentei usar menos jargão e traduzir
a linguagem técnica para um vocabulário mais digerível. Eu tinha esperança.
Esse texto recebeu alguns comentários positivos e foi adotado por uma das associações. E foi a semente para este blog.
É isso aí! Há seis anos, comecei o blog Tratando a Acondroplasia para compartilhar o
que aprendia com todos os interessados em entender a acondroplasia e
o trabalho em andamento para vencer a mutação genética que leva a essa
displasia esquelética.
Existem dois tipos de artigos publicados no blog. O primeiro compreende revisões dos mecanismos da desordem
genética e no segundo estão aqueles que analisam estratégias potenciais de tratamento. No
entanto, procuro incluir um pouco
de base sobre os mecanismos envolvidos em cada estratégia nos textos sobre terapias.
Até hoje, o blog recebeu mais de 300 mil visitas. Quando reviso as estatísticas, posso ver que a maioria dos
visitantes está mais interessada nas potenciais terapias e soluções
para a acondroplasia, o que me faz concluir que o blog está no caminho certo.
O blog tornou-se um pouco silencioso ultimamente, como mencionei em um artigo anterior. E, como eu disse antes, isso tem mais a ver com a minha percepção de uma
ligeira diminuição em tópicos que podem ser interessantes para os
leitores do que por qualquer outro motivo.
Novidades, novidades, novidades
E, apenas para nos manter atentos e atualizados, estou feliz em
compartilhar com você que existe mais uma estratégia que pode se tornar
uma opção forte para o tratamento da acondroplasia.
Apenas
dois dias atrás, um empresa de investimentos de risco (venture capital) em biotecnologia chamado BridgeBio anunciou o estabelecimento da QED Therapeutics, uma nova iniciativa para
continuar a pesquisa com o BGJ398, uma pequena molécula agora chamada
infigratinib, que foi projetada para bloquear FGFRs, mas que tem mais
afinidade com o FGFR3. Ela foi projetada com o objetivo de tratar vários tipos de câncer que usam FGFRs para crescer. Para saber mais sobre a QED, visite seu site aqui.
O infigratinib já foi testado em um modelo animal de acondroplasia e mostrou resultados promissores convincentes (1). Este
estudo liderado por Laurence Legeai-Mallet, uma mestra em displasias
relacionadas ao FGFR3, também foi revisado aqui no blog em 2016: Tratando a acondroplasia: NVP-BGJ398, um inibidor de tirosina quinase, restaura o crescimento ósseo em um modelo de acondroplasia.
Esta revisão começa com um pequeno resumo da acondroplasia e da biologia por trás dessa displasia esquelética. Ela pode ajudar-lhe a ter uma visão melhor da questão (como eu disse, misturo tópicos ...).
Em resumo, o infigratinib foi administrado em doses inferiores às
destinadas ao tratamento do câncer e, basicamente, conseguiu resgatar o
crescimento ósseo no modelo testado. É
importante notar que, tendo já alcançado ensaios clínicos para câncer, o
infigratinib mostrou um perfil de segurança equilibrado. Agora, ele deve ser testado no contexto do corpo em desenvolvimento e a razão é simples. Embora
a molécula mostre mais afinidade com o FGFR3, também pode bloquear
outros FGFRs, então precisamos entender se haveria problemas de
segurança no organismo em crescimento exposto ao infigratinib antes
de se iniciar o desenvolvimento clínico em crianças. Se for provado ter segurança, então a justificativa para seu uso seria forte,
já que ele bloqueia diretamente a proteína que causa a acondroplasia em
comparação com outras drogas, como o vosoritide, que funciona indiretamente.
Estes são tempos agitados. Alguns
anos atrás, eu ouvi de um investigador de renome que "no futuro próximo
o problema não será tratar ou não acondroplasia. O problema será escolher qual
medicamento usaremos para tratá-la". Isso será verdade para as novas gerações.
Obrigado
Obrigado pelo seu interesse no blog Treating Achondroplasia. Espero que continue sendo útil para você!
Referências
1. Komla-Ebri Det al.
Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related
dwarfism in mouse model. J Clin Invest 2016;126(5):1871-84. Acesso livre.
Friday, February 2, 2018
Thursday, February 1, 2018
Treating achondroplasia: sixth year online and news
Anniversary
Nine years ago, I was participating in a small online discussion group, in a time when blogs and social media were not yet as popular as now, and published a small summary of what I was reading about achondroplasia.
At that time, having already talked with a number of investigators in the field and with a few representatives of advocacy groups I realized that the technical information and advances I was seeing in the literature were difficult to reach by the interested community. In that short article, my focus was perspective rather than reviewing what experts were doing already so well. I put together all potential strategies I found in the literature that could be used to treat achondroplasia in a few paragraphs. As most of the participants on that discussion group had no medical background I tried to use less heavy jargon and translate technical language to a more digestible vocabulary. I had hope.
That text received some positive feedback and was adopted by one of the advocacy groups. And was the seed for this blog.
That's it! Six years ago I started the Treating Achondroplasia blog to share what I was learning with all those interested in understanding achondroplasia and the ongoing work to beat the genetic mutation that leads to this skeletal dysplasia.
There are two kinds of articles published in the blog. The first type comprises reviews of the genetic disorder mechanisms and in the second there are those reviewing potential strategies. Nevertheless, I keep trying to mix both topics, to give a bit of background on the mechanisms involved in each strategy.
As of today, the blog has received more than 300K visits. When I review the statistics I can see that most visitors are more interested in the potential therapies and solutions for achondroplasia, so I think the blog is in the right track.
The blog has become a bit silent lately, as I mentioned in a previous article. And as I said then, this has more to do with my perception of a slight decrease in topics that may be interesting for the readers than for any other reason.
News, news, news
And, just to keep us on track and aware, I am happy to share with you that there is one more strategy that may become a strong option for the treatment of achondroplasia.
Just two days ago, a biotech venture called BridgeBio announced the establishment of QED Therapeutic, a new initiative to continue the research with BGJ398, a small molecule now called infigratinib, that was designed to block FGFRs, but which has more affinity with FGFR3. It was designed aiming to treat several kinds of cancer that use FGFRs to grow. To learn more about QED, visit their website here.
Infigratinib has been already tested in an animal model of achondroplasia and showed compelling promising results (1). This study leaded by Laurence Legeai-Mallet, a master in FGFR3-related dysplasias, was also reviewed here in the blog in 2016: Treating achondroplasia: NVP-BGJ398, a tyrosine kinase inhibitor, restores bone growth in a model of achondroplasia. This review starts with a tour through achondroplasia and the biology behind this skeletal dysplasia. It may help you to have a better view of the landscape (as I said, I mix topics...).
In short, infigratinib was given in doses lower than those intended for the treatment of cancer, and basically was able to rescue bone growth in the tested model. It is important to note that, having already reached clinical trials for cancer, infigratinib showed a balanced safety profile. Now, it must be tested in the context of the developing body and the reason is simple. Although the molecule shows more affinity to FGFR3, it can also block other FGFRs, so we need to understand whether there would be safety issues in the developing organism exposed to infigratinib before it reaches the clinical development in children. If proven to be safe, then the rationale for its use would be strong as it directly targets the protein that causes achondroplasia compared to others such as vosoritide, that works indirectly.
These are exciting times. Some years ago, I heard from a renowned investigator that "in the near future the problem won't be to treat or not achondroplasia. The problem will be to decide which drug we will use to treat it". This will be true for the new generations.
Thank you
Thanks for your interest in the Treating Achondroplasia blog. I hope it keeps being useful for you!
References
1. Komla-Ebri Det al. Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. J Clin Invest 2016;126(5):1871-84. Free access.
Nine years ago, I was participating in a small online discussion group, in a time when blogs and social media were not yet as popular as now, and published a small summary of what I was reading about achondroplasia.
At that time, having already talked with a number of investigators in the field and with a few representatives of advocacy groups I realized that the technical information and advances I was seeing in the literature were difficult to reach by the interested community. In that short article, my focus was perspective rather than reviewing what experts were doing already so well. I put together all potential strategies I found in the literature that could be used to treat achondroplasia in a few paragraphs. As most of the participants on that discussion group had no medical background I tried to use less heavy jargon and translate technical language to a more digestible vocabulary. I had hope.
That text received some positive feedback and was adopted by one of the advocacy groups. And was the seed for this blog.
That's it! Six years ago I started the Treating Achondroplasia blog to share what I was learning with all those interested in understanding achondroplasia and the ongoing work to beat the genetic mutation that leads to this skeletal dysplasia.
There are two kinds of articles published in the blog. The first type comprises reviews of the genetic disorder mechanisms and in the second there are those reviewing potential strategies. Nevertheless, I keep trying to mix both topics, to give a bit of background on the mechanisms involved in each strategy.
As of today, the blog has received more than 300K visits. When I review the statistics I can see that most visitors are more interested in the potential therapies and solutions for achondroplasia, so I think the blog is in the right track.
The blog has become a bit silent lately, as I mentioned in a previous article. And as I said then, this has more to do with my perception of a slight decrease in topics that may be interesting for the readers than for any other reason.
News, news, news
And, just to keep us on track and aware, I am happy to share with you that there is one more strategy that may become a strong option for the treatment of achondroplasia.
Just two days ago, a biotech venture called BridgeBio announced the establishment of QED Therapeutic, a new initiative to continue the research with BGJ398, a small molecule now called infigratinib, that was designed to block FGFRs, but which has more affinity with FGFR3. It was designed aiming to treat several kinds of cancer that use FGFRs to grow. To learn more about QED, visit their website here.
Infigratinib has been already tested in an animal model of achondroplasia and showed compelling promising results (1). This study leaded by Laurence Legeai-Mallet, a master in FGFR3-related dysplasias, was also reviewed here in the blog in 2016: Treating achondroplasia: NVP-BGJ398, a tyrosine kinase inhibitor, restores bone growth in a model of achondroplasia. This review starts with a tour through achondroplasia and the biology behind this skeletal dysplasia. It may help you to have a better view of the landscape (as I said, I mix topics...).
In short, infigratinib was given in doses lower than those intended for the treatment of cancer, and basically was able to rescue bone growth in the tested model. It is important to note that, having already reached clinical trials for cancer, infigratinib showed a balanced safety profile. Now, it must be tested in the context of the developing body and the reason is simple. Although the molecule shows more affinity to FGFR3, it can also block other FGFRs, so we need to understand whether there would be safety issues in the developing organism exposed to infigratinib before it reaches the clinical development in children. If proven to be safe, then the rationale for its use would be strong as it directly targets the protein that causes achondroplasia compared to others such as vosoritide, that works indirectly.
These are exciting times. Some years ago, I heard from a renowned investigator that "in the near future the problem won't be to treat or not achondroplasia. The problem will be to decide which drug we will use to treat it". This will be true for the new generations.
Thank you
Thanks for your interest in the Treating Achondroplasia blog. I hope it keeps being useful for you!
References
1. Komla-Ebri Det al. Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. J Clin Invest 2016;126(5):1871-84. Free access.
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