Index (EN)

Hi, here you will find the English versions for all articles published in the Portuguese section of this blog.

The articles provide a step-by-step discussion about scientific aspects of achondroplasia. We review the mutation origin and the molecular mechanisms of achondroplasia. However, most of the articles intend to share information about potential therapeutic strategies for achondroplasia.

The blog started as a personal collaboration initiative with Growing Strongerthe non profit, parents’ organization devoted to stimulate and fund research on pharmacological therapies for achondroplasia.


2018

30/04/2018.Treating achondroplasia: a review of the therapy landscape with focus on statins
14/03/2018.Treating Achondroplasia: frequent questions about treatment
01/02/2018.Treating achondroplasia: sixth year online and news
11/01/2018.Treating achondroplasia: TransCon CNP showed positive results in pre-clinical tests
2017

25/10/2017.Treating achondroplasia: thirty months with vosoritide
07/08/2017.Treating achondroplasia: update on the current potential therapies 

11/01/2017. Treating Achondroplasia: fifth year online 

2016

12/12/2016.Treating Achondroplasia: Phase 3 study with vosoritide started in Australia 
19/10/2016. Treating Achondroplasia: results from the fourth cohort of the phase 2 study with vosoritide have been released
18/10/2016. Treating Achondroplasia: highlights from the recent literature: Fluazuron and CNP
24/09/2016. Vosoritide one year phase 2 results of the third cohort to be presented in the next ASHG 2016 meeting
17/05/2016.Treating achondroplasia: NVP-BGJ398, a tyrosine kinase inhibitor, restores bone growth in a model of achondroplasia 
21/04/2016. Treating achondroplasia: news about the clinical development of vosoritide
10/03/2016. Stopping FGFR3 production to treat achondroplasia (part 1)
29/02/2016. The Rare Disease Day 2016
11/01/2016. Treating Achondroplasia: fourth year online 
05/01/2016. FGFR4: a problem for ligand trap therapeutic strategies in achondroplasia? 

2015

06/11/2015. Treating achondroplasia: the role of Tyrosine Kinase Inhibitors
27/09/2015. Treating achondroplasia: B-701, a new antibody anti-FGFR3 and more news 
03/08/2015. Biomarin announces first patient in the fourth cohort of the phase 2 study
30/07/2015. Treating achondroplasia: news from the vosoritide clinical development program
05/07/2015. Treating achondroplasia: meclizine has positive effects for the foramen magnum in a model of achondroplasia
17/06/2015. Vosoritide (BMN-111) induces 50% increase in growth velocity in children with achondroplasia
28/05/2015. Treating achondroplasia: BMN-111 and the catch up growth phenomenon
17/05/2015. Treating achondroplasia: news about BMN-111
30/03/2015. Treating achondroplasia: the history of the development of BMN-111
14/03/2015. Treating achondroplasia: just one's right
31/01/2015. Biomarin updates the information about the BMN-111 Phase 2 study in clinicaltrials.gov
20/01/2015. The Treating Achondroplasia Blog: Third Year Online

2014

15/12/2014. Treating achondroplasia with meclizine / meclozine
01/12/2014. Treating achondroplasia with statins
20/08/2014. FGFR3 and growth plate literature news 
18/06/2014. Treating achondroplasia: where we are now
31/05/2014. FGF18, a key player for bone growth
19/05/2014. News from Biomarin about BMN-111
07/03/2014. Treating achondroplasia: NC-2, a new CNP analogue
10/02/2014. Biomarin includes the BMN-111 phase 2 study at the ClinicalTrials.gov
03/02/2014. Growing Stronger and LPA to receive proposals for funding research on skeletal dysplasias
27/01/2014. Blocking the MAPK cascade to treat achondroplasia 
20/01/2014. Why do chondrocytes stop in achondroplasia? part 2 
14/01/2014. Biomarin announced that the Phase 2 study of BMN-111, the first potential pharmacological therapy for achondroplasia, has just started 
08/01/2014. Treating achondroplasia: second year online 

2013

25/12/2013. Why do chondrocytes stop in achondroplasia?
11/12/2013. Meclizine / meclozine for achondroplasia? 
30/11/2013. Natriuretic peptides for achondroplasia: what's new? 
02/11/2013. The First International Dwarfism Congress of Portugal 
19/10/2013. Learning about signaling cascades 
12/10/2013. New evidence of CNP signaling cascade relevance in bone growth
20/09/2013. A new ligand trap strategy to treat achondroplasia 
17/09/2013. BMN-111 phase 2 study has been authorized by the FDA 
14/09/2013. On air, the Brazilian reference site for bone dysplasias 
10/09/2013. More news about BMN-111
08/09/2013. Repurposing of old drugs: is there an opportunity for achondroplasia?
07/09/2013. BMN-111 in The International Skeletal Disease Society - ISDS 2013 Meeting
01/09/2013. Stem cell therapy for achondroplasia?
25/07/2013. BMN-111 news from July 25th Biomarin conference call
08/07/2013. The Blog has now a Glossary Page
16/06/2013. Interfering in the production of FGFR3: a potential strategy to treat achondroplasia 
28/05/2013. Exploring the use of aptamers to treat achondroplasia
09/05/2013. Researchers identify a new class of FGFR inhibitors
04/05/2013. Biomarin updated information about the clinical development study of children with achondroplasia
26/04/2013. The mechanism of action of CNP in the FGFR3 pathway showed by a new study
30/03/2013. Capturing fibroblast growth factors to treat cancer. Could this strategy be used to treat achondroplasia?
05/02/2013. Treating achondroplasia with anti-FGFR3 specific peptides
30/01/2013. The Acondroplasia - Achondroplasia blog: first year online
26/01/2013. The Rare Disease Day 2013
19/01/2013. Developing medicines for rare conditions
04/01/2013.Treating achondroplasia: the great challenge ahead 
01/01/2013. Treating achondroplasia: concepts and misconcepts about the potential therapies in development

2012

14/12/2012. Achondroplasia and the new potential clinical therapies: who can benefit from them?
12/01/2012. A quick introduction

18 comentários:

  1. Good day I Morrys C. Kaysermann influences include to ask a question about the treatment of achondroplasia your mail if possible.

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    Respostas
    1. Hi Oleg, can you repeat your question. I guess there was some trouble with the translator used. If you have a question about achondroplasia, you could make it here. It might be interesting to other readers, too.

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  2. Morrys hi. If the test meclizine on children up to 6 years with the disease achondroplasia. And if such research is conducted, I would like to have a calculation of doses meclizine based on the weight of the child?

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  3. Hi Oleg, the Japanese group exploring mecilizine for achondroplasia said that they used doses within therapeutic ranges in their animal model. However, it is too early to make assumptions about the potential effect of this medicine in achondroplasia. Please, read carefully the original article. I made a summary in this article: http://tratando-acondroplasia.blogspot.com.br/2014/12/treating-achondroplasia-with-meclizine_15.html. We simply don't know, at this point, if this would be really safe and efficient in long term. Remember that this medicine has several other effects, typical of old anti-histaminics.

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  4. Dr. Morrys,

    other than restoring long bone growth, what effect does Biomarin expect for verositide when it come to the front bossing, indented bridge of the nose, sleep apnea, stenosis and other related skeletal conditions caused by Achondroplaysia?

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    Respostas
    1. Hi Brian, good questions. According to the pre-clinical studies performed with CNP and BMN-111, we could expect that bones which grow through the process we may call "endochondral development" should all respond some way to these peptides. This includes the long bones (limbs) and spine, as well as some of the head bones. Those studies showed that mice treated with CNP restored at least part of the facial bone growth. As the bones of the cranium grow through another process (called intramembranous) one should not expect major changes in the cranium patterns (frontal bossing). It is early to say how much vosoritide will be able to restore the facial bone growth (nose bridge, etc.), nor we can tell much about long term effects of this peptide on other orthopedic complications seen in achondroplasia. Nevertheless, assuming that the drug will work restoring, at least partially, the growth program impaired by FGFR3, in long term we might see less leg bowing, less lumbar lordosis, less elbow restriction, less limb disproportion, less joint overload and tilt (and for this less early arthritis). Regarding foramen magnum stenosis leading to sleep apnea, it is difficult to predict if the peptide would be efficient even in younger kids, since there is pre clinical evidence that the bones forming the cranial base are already "merged" by or soon after birth. However, for later potential stenosis, there could be benefit, too. If you are following the blog, you might have already read the recent comment about meclizine, which was tested in pregnant mice, with positive results at the foramen magnum level.
      I hope this helped you.
      Regards,
      Morrys

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  5. Dr. Morrys,

    in reviewing Biomarin's recent update, it appears that the study completion date has been extended from January 2017 to January 2019. Why is that? Does this mean that verositide won't be commercially available until 2019 at the earliest? If so, why now the delay? It seemed that they were well on there way to getting this drug commercially available for early 2017.

    Brian

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  6. Hi Brian, good observation. I think the sponsor could be adjusting timelines to accommodate the long term extension study or possible delays in the drug development. According to the last public meetings, they are planning to start the phase 3 study in the first quarter of 2016, and there are ongoing discussions with regulatory authorities around the duration of the trial (6 months or 1 year), so again, the dates might have been adjusted to cover a possible extended drug development period.
    I hope this helps you.
    Regards,
    Morrys

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  7. dr nice to see your blog

    my name is desi, i'm from indonesia, i have doughter is achondroplasia, now 10 moth old, but My daughter is very weak
    doctor
    What should I do, I was blind about achondroplasia
    help me pls

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    Respostas
    1. Hi Desi,
      First, do not despair!
      Many kids with achondroplasia will experiment some delay in their motor development and this is not something to worry about. This delay may occur due to low muscle tonus caused by the imbalance between bone vs. muscle growth. However, a minority of children with achondroplasia may suffer with spinal cord compression, which might be seen firstly as mild impairment in some motor skills, especially in the lower limbs. Others may have respiratory trouble. That's why it is good to have a consultation with a pediatric neurologist with experience in achondroplasia to rule out any potential problems in this area. Look for a reference center for skeletal dysplasias in your area. Normally, they will have professionals with more expertise to help and guide you.
      You can read these two good free guidelines available showing how to follow up with your kid's development: A.http://pediatrics.aappublications.org/content/116/3/771.full-text.pdf); B. http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2011.04050.x/epdf. This following article shows the developmental milestones for kids with achondroplasia: http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8749.2011.04050.x/epdf.
      I hope this help you,
      Kind regards,
      Morrys

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  8. Hello Dr. Morrys! Thank you very much for an interesting and useful blog!

    Would you answer some questions about the article "Treating achondroplasia: NVP-BGJ398, a tyrosine kinase inhibitor, restores bone growth in a model of achondroplasia"?

    1) Do I understand correctly, that BGJ398 is an inhibitor of fibroblast growth factor receptors (FGFRs) and it provides a benefit by treatment of achondroplasia?
    2) C-type natriuretic peptide (CNP) is a drug promoting bone growth, right?
    3) Is a Meclozine a possible medicine for treatment of achondroplasia?

    Thank you in advance
    Sergei, Russia
    achondroplasia@yandex.ru

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    Respostas
    1. Hello Sergey and Welcome!
      1. BGJ398 is a FGFR inhibitor that was tested in an animal model of achondroplasia with positive results. The article points to the reference.
      2. CNP is a natural peptide produced within the growth plates. There is a CNP analogue, vosoritide, which is being tested in children with achondroplasia.
      3. meclizine/meclozine has been explored in animal models for achondroplasia.
      All of these drugs might become useful for achondroplasia provided they prove they are truly safe and efficient to treat the bone growth arrest caused by the the mutant FGFR3.
      Check the index page to review previous articles of the blog reviewing all of these strategies and several potential others.
      Regards,
      Morrys

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  9. Dear Dr. Morrys, thank you very much for your blog that I read with much interest.
    My name is Giacomo I am the father of a newborn baby with achondroplasia.
    I would like to ask you a couple of question about BMN 111 trial on infants.
    I know data are not available yet but I hope you can give me at leat a theoretical answer.

    1 What effect of CNP/Vosoritide in other cartilaginous tissues such as the joints, ears, nose and trachea?

    2 What effect of Vosoritide on distal bones (hands and feet)?

    3 What happen if you start the trial, then the clinical trial ends after one or two years and you have to wait two or three years for commercialization? what can happen to the body in the meanwhile?

    Thank you very much.

    All the best,

    Giacomo

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    Respostas
    1. Hi Giacomo, thanks for your interest in the blog. You made good questions, let´s see if I can answer them.
      1. It seems that most of the effect of CNP in bone development is seen within the growth plate. Although several tissues may express CNP or its related receptor, they are not always present in the same environment at the same time. In many reviews of the field I have not seen yet any special concern about relevant activity of CNP in other cartilaginous tissues.
      2. CNP will exert its natural effects in all bones that undergo what is called "endochondral bone formation". This includes almost all bones in the body with the exception of the skull and part of the clavicle. Therefore, CNP should also work in hand and feet bones, too.
      3. After the phase 2 study, the developer of vosoritide opened a long term study in which participants from the phase 2 could keep receiving the treatment. This study is still active (check in clinicaltrials.gov). It is very unlikely that the infant study would not have a similar continuation after its end.
      I hope this helps!
      Kind regards,
      Morrys

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    2. Dear Dr Morrys,
      thank you very much for your answer and again thank you for your interest in this rare genetic condition.
      It is very precious to have your explanation and update on the current researches. I hope that more good news will come in 2018.

      I came across this article on the effect of H. Sabdariffa on chondrocytes, but with my limited scientific knowledge I cannot understand if it would be wise to introduce this beverage in my child diet in the future.
      https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4595466/
      I couldn’t find any following research on this topic. It would be great to have your opinion.
      Kind regards
      Giacomo

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    3. Hi Giacomo,
      This is not the first study on herbal extracts and their effects in chondrocytes. Regarding this particular article I feel that there might be potential weaknesses in the study design and/or report that could prevent any solid conclusion. For instance, they mention the effect of the plant extract in one of the enzymatic components of the FGFR3 pathway (ERK1/2) but neither quantify nor show this effect in their paper (picture, chart, etc.). It seems, based on the information they provide, that the extract could be useful to reduce or minimize the joint osteoarthritic process, rather than do something specific to the open growth plate, but as I said, the published results would not allow any solid conclusion.
      From another standpoint, although it is not expected that an herbal extract would be harmful, one should pay attention to the fact they didn't use the original extract but a further concentrated form to perform their main tests, so there is a risk that the original material obtained for the study could be useless in the real life.

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    4. Thank you very much for your answer and again for your interesting blog.
      All the best

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