Treating Achondroplasia: how to improve the healthcare for achondroplasia

A conference and a survey

A few months ago I was invited to speak at a conference about how the community sees the healthcare and general support for achondroplasia. The conference had clinical and scientific experts from all over the world.

Given my involvement with achondroplasia, I have my own perceptions about the ups and downs of care, but I wanted to have a broader view that I could present to the other experts during my talk. I wanted to hear from families and people who deal directly with health issues, so I started a short survey in three achondroplasia-related groups in Facebook (Fb; two international and one based in Brazil). The survey was not about calculating rates of this and that, but to understand people's view about the healthcare for achondroplasia.

In summary, the purpose of the survey was to gather impressions of what works well and what doesn't when someone needs healthcare or support from the healthcare system. I have extracted the feedback received from Fb group members from different countries around the world and collated them, and also added real testimonies collected from Fb groups. All information that could lead to personal identification was redacted. More than giving my own opinion, the way I presented the data had one single goal, which was to provide the experts in the conference with points-of-view about healthcare that are not frequently shared with them in their daily practice.

Of course, the message, or messages, given during that presentation are far from approaching all aspects involved in the care and support individuals with achondroplasia and their families need and deserve. My talk basically emphasized an important issue people all over the world face when seeking for healthcare and/or support. However, I believe that what I showed was able to move the audience towards the right direction. I promised to publish the results of the survey, which is what I am doing now, by sharing with you the presentation I gave and I am really grateful to all those members that provided their opinions and insights. Thank you!

Treating Achondroplasia: seven years online and counting

A bit of history

The blog Treating Achondroplasia is celebrating seven years online. The blog has received over 350K visits so far and I hope it is being useful for the visitors. It was created to share knowledge and empower those interested in driving the changes we need for achondroplasia.

I can't help feeling amazed about all the developments I've seen since I published the first article here. The annual number of scientific publications about achondroplasia did not really increase in the last ten or fifteen years (just a bit, as we see in Pubmed; Figure 1), but the scope of the publications has clearly changed over the years.

Figure 1. Number of publications/year about achondroplasia.

Information provided by Pubmed, based on the search for the term "achondroplasia".

For instance, a significant number of studies helped to better understand the molecular mechanisms underlying the FGFR3 mutation leading to achondroplasia. New growth charts (Argentina, Australia, Europe, US) became available to help parents and healthcare providers to track the development of affected kids. Several other works were published about development milestones, and also focusing in management of medical complications, including surgical aspects, from dealing with spinal stenosis and leg bowing to the limb lengthening techniques. We also see that quality-of-life and early diagnosis have also been given more attention lately. Although it is clear that the research for specific therapies has also grown, the number of them is still relatively low. Therapies for achondroplasia might certainly be useful for other dysplasias, but the risk to develop them is high, so...

The low hanging fruit 

The risk is high. This makes me recall a passage of my own development curve. Back to 2009, during a visit to one of the world greatest experts in FGFR signaling and the inventor of one of the first tyrosine kinase inhibitors, in the heart of one of the most renowned US universities, I heard that the research for therapies for genetic disorders like achondroplasia was scarce because it was too risky. He said that large companies would not focus on rare disorders where the landscape was yet to be mapped. Instead they would prefer to drive on paved roads, taking less risk in their endeavors (picking the fruit at the reach of their arms). Tackling rare conditions was a sort of venture reserved for small biotechs (it still is, indeed!). You can imagine how I was feeling when I left that meeting. Some mix between a sense of privilege to have just talked to and learned from that master and at the same time hit by that disheartening concept he told me. Yes, I was already in the pharma industry, but still had an academic heart. What he said was a kind of revelation for me.

Just after that meeting I went to Boston for the International Skeletal Dysplasias Congress, a wonderful opportunity to meet experts from all over the world. The achondroplasia I knew till then was mostly that described in the literature and from my little previous experience in assisting a few affected patients over the years. Talking with those passionate scientists and physicians and watching their presentations gave me new perspectives. One of those physicians, when hearing that I was in the pharma industry, immediately reacted with some sort of contempt: "oh, you work for pharma", followed by one of those looks we easily find in our emoji libraries. I asked him why he was, let's say, upset about that, and he replied saying that "we" (pharma) were not trustworthy. Another punch in just a couple of days. His previous experience with the industry made him reacting that way, a kind of communication gap between them. I told him I was not simply a physician, and I was not simply a pharma R&D professional. I was also a father. This was the kind of combination not easy to find.

It took me one year more to gain his respect. We have met several times after that first congress, but in the end, it was his hand which pointed out to the right direction towards the first clinical trial for achondroplasia when the opportunity came.

The fruit not easy to pick

There are more than seven thousand rare disorders described, and less than 10% have any therapy approved. Despite several incentives promoted by regulatory agencies aiming to increase the research towards therapies for genetic and rare disorders, there is still little effort applied to find solutions for them.

Nevertheless, the interest about achondroplasia has grown in the last five years, with several new approaches being explored, and some being seriously taken into clinical development. I believe this happened as a consequence of the preliminary positive results showed by studies with the C-type natriuretic peptide (CNP) and its first analogue in development, vosoritide. You see, someone needs to chart the new territory and to show that there is potential there. For achondroplasia, cheers for the pioneer Japanese developers of the CNP concept and to the biotech which brought it into the clinic in the form of vosoritide. Others are following, and we now have a second CNP analogue (this road is already paved) and a couple of other strategies already in the clinic (see below). More could be done but, for a rare disorder, these are great news.

A busy year ahead

The new year has just started but we already have news in the horizon. Biomarin announced that the phase 2 study in infants and toddlers is ongoing, and that there were no adverse events in the older cohort so far (Figure 2). 

Figure 2. Biomarin, slide 15 from the presentation on January 7 (2019).

Full presentation can be accessed here.

Meanwhile, Ascendis announced that the start of the phase 2 study with their TransCon CNP is planned for the third quarter (Figure 3) and QED, the developer of infigratinib, is showing in their "Pipeline" webpage that they are planning the start of their natural history study during 2019 and that the next steps would include a phase 1/2 trial (Figure 4).

Figure 3. Ascendis Pharma, slide 56 from the presentation on January 7 (2019).

This slide summarizes results from the phase 1 study with TransCon CNP and lists the next development step. The full presentation can be accessed here.

 
Figure 4. QED Therapeutics pipeline.

Adapted from QED Therapeutics website (free access to the public). Original image can be found here.

The interesting piece here is that the way this expression "phase 1/2 trial to follow" was used could imply that the plan would be to perform an integrated phase 1/2 study, in a potential adaptative design, where after establishing PK and PD in a first group of volunteers (possibly affected children?), subsequent cohorts of participants could start being dosed in a typical phase 2 study fashion. This would only be possible because infigratinib has already all the pre-clinical work done and several clinical trials performed for cancer. Such a design may help expediting the development of infigratinib towards approval, if proven safe and efficient in achondroplasia. 

The change 

Just ten years ago there was no sign for any potential treatment for achondroplasia and, for long time, people with achondroplasia, and by extension, with many other forms of skeletal dysplasias, had no sight that their bone disorders one day would be considered for therapy. Generations have grown under this perspective and dealing with many daily social and medical challenges to say the least, so nothing more natural than the people to build a strong sense of identity. This sense of identity helped creating a solid and fierce community that has been key for many conquers in the social, political and healthcare space.

Science evolves and drives human progress, although it is not linear or necessarily constant. There are jumps and falls in between. However, many chronic and debilitating diseases now have treatments that control or slow down their pace or even revert them. In our days, more and more forms of cancer can be cured with the right therapies, and new and more specific drugs are being developed to beat this once devastating disease.

 

Although a little behind, the knowledge on genetics is growing exponentially, and genetic therapies are already being designed to treat diseases of all sorts, from cancer and diabetes to infectious diseases and genetic disorders. In the near future, we will be able to conquer even more diseases that were unbeatable in the past. This is true for cancer, this will be true for skeletal dysplasias.

So, the change is coming and it's time to see beyond the status quo. Let's embrace the future we see ahead of us, and let's help the new generations to benefit from all the knowledge and progress that are on the horizon. Let's work to give our kids a better future, with more health, more quality of life and more possibilities. Let's give them hope. This is what this blog is about. This has been my pledge from the beginning. It is still mine for 2019 and beyond.

Treating Achondroplasia: frequent questions about treatment

Disclaimer

I have no employment relationship or receive any compensation or incentive from any company researching medications or treatments for achondroplasia. What I write is based on the knowledge acquired from the scientific literature and the information published by the respective companies.


Introduction
 
I have been receiving many questions about how the research for achondroplasia treatments is going and more specifically about vosoritide. As the treatment is a relevant theme to many, I thought it would be useful to share my knowledge with everyone in the form of questions and answers.

All product information in this text is in public domain and referenced. Where there is no bibliographical reference the text reflects my personal opinion.

Visit the index page to learn more about the topics covered here. The blog contains many reviews on achondroplasia and on basically all potential treatments already published in the scientific literature so far. 

• What is vosoritide?

Vosoritide, also known as BMN-111, is an improved copy of a substance produced naturally by the human body, called the C-type natriuretic peptide (CNP) (1). CNP is one of the substances that positively regulate the growth of the bones, Vosoritide does exactly what CNP does: it stimulates the growth of the bones. 

• What is the reason for using CNP or vosoritide in achondroplasia?

Research has shown that CNP reduces the activity of FGFR3, the mutated protein in achondroplasia. FGFR3 is a bone growth regulator, but works naturally as a brake. However, due to the mutation, FGFR3 becomes so active that it prevents normal bone growth. The natural function of CNP (and by similarity, of vosoritide) is to reduce the action of FGFR3, that is, it releases the brake. Another important aspect of the action of the mutant FGFR3 is that it also reduces the amount of CNP present in the cartilage growth plate. Therefore, providing CNP or CNP analogs helps bone growth in achondroplasia (2-6).

• What is the risk of using CNP or vosoritide in children with achondroplasia?

In animal studies, CNP and vosoritide showed a good safety profile (3). CNP belongs to a family of substances that interferes with blood pressure. It is expected that the CNP application will have a negative effect on blood pressure. In fact, all studies or reports in humans published on vosoritide so far indicate that there is a slight drop in blood pressure after its application. This reduction is considered to be mild and transitory and rarely accompanied by any symptoms. To date, there is no other relevant adverse effect published on vosoritide (7).

• What is the risk of using vosoritide in the long term?

CNP, and therefore its copies, have a very short action time and do not accumulate in the body. These substances are quickly eliminated by the body. Thus, in addition to not producing short-term problems, they are not expected to produce long-term toxic effects. However, only time can confirm if there are in fact no undesirable consequences with the use of the medication in the long term. 

• What to expect from treatment with vosoritide?

If vosoritide works as expected, it will promote more growth of the body's bones. In addition to a likely higher final stature, with longer limb bones, it is estimated that treatment could reduce the large number of orthopedic and neurological complications associated with achondroplasia. We will only be able to know about this in the future as the children in treatment reach adulthood. 

• Does vosoritide really work?

According to test results published so far, vosoritide was able to increase bone growth rate by about 40-50% on average in treated children (8). This approximates the growth speed of treated children to that of children not affected by the mutation. Only over time we will know if it will maintain this rhythm in the long run. 

• Who will benefit from the use of vosoritide (or any treatment for achondroplasia)?

Only individuals who still have "open" bone growth plates can benefit from growth-promoting drugs. Growth plates are small specialized structures present at the ends of long bones. They are responsible for stretching the bones. It is exactly in the growth plates that FGFR3 and CNP work.

Growth plates close at the end of puberty, representing the end of the growth period of the body. Unfortunately, CNP, vosoritide or any other treatment aimed at blocking the action of FGFR3 will cease to be useful when the individual reaches adulthood because there will be no more growth activity then. 

• When to start treatment with vosoritide for the treatment of achondroplasia (or any other medication that is approved to treat it)?

Since the effects of the FGFR3 mutation begins already durign pregnancy, it seems essential that treatment should be started as soon as possible, probably soon after birth. Growth is a natural phenomenon with expiration date, as we have seen above. It is likely that the longer the treatment the better the final outcome will be when the individual reaches adulthood. 

• As for vosoritide, when will it become available?

Vosoritide is still in clinical trials to confirm its effectiveness and safety. These tests are mandatory and controlled by the agencies that regulate medicines (in US, the agency is the FDA).

Vosoritide is being tested in a Phase 3 study, and the results of this study will allow the laboratory developing it to obtain the license to market it provided it is successful in the tests. The current prediction by the developer is that the results of the phase 3 study will be available in the second half of 2019 to be submitted to the FDA (9). Based on this prediction, if approved, it may be available in the United States at the beginning of 2020. Availability in other countries will depend on the strategy of the developer of vosoritide and the speed of the drug approval process of the regulatory agencies in those other countries. 

• Are there other medications being tested?

There are several other initiatives to identify and test potential treatments for achondroplasia. A list of all these initiatives can be found here. Some of these initiatives may reach the clinical development stage in the near future.

For example, the developer of the molecule known as TA-46 announced in February 2018 that it wants to start the Phase 1 study soon (10). Another company that is developing a new form of CNP known as TransCon-CNP also intends to request authorization to start clinical studies soon (11). As a consequence of a study in an animal model of achondroplasia in which it showed promising results, a company was created to continue the development of the molecule NVP-BGJ398 (12,13).

These are just a few examples, there are other initiatives underway, but I believe these are the most promising at the moment. All these initiatives are still far from the pharmacy, but some of them, if successful, could be available in about 4-5 years .

I hope this little review helps to clarify some doubts. The blog Treating Achondroplasia is active. New articles will be published whenever there is any theme that may interest readers.

References 

1. Wendt DJ et al. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism. J Pharmacol Exp Ther 2015; 353(1):132-49. Free access.

2. Krejci P et al. Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis. J Cell Sci 2006; 118: 5089-00.

3. Lorget F et al. Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. Am J Hum Genet 2012;91(6):1108-14.

4. Nakao K et al. Impact of local CNP/GC-B system in growth plates on endochondral bone growth. Pharmacol Toxicol 2013; 14 (Suppl 1):48.

5.Yasoda A et al. Systemic Administration of C-Type Natriuretic Peptide as a Novel Therapeutic Strategy for Skeletal Dysplasias. Endocrinology 2009;150: 3138–44.

6.Yasoda A and Nakao K. Translational research of C-type natriuretic peptide (CNP) into skeletal dysplasias. Endocrine J 2010; 57 (8): 659- 66.

7. Hoover-Fong J et al. Vosoritide in children with achondroplasia: Updated results from an ongoing Phase 2, open-label, sequential cohort, dose-escalation study. Abstract presented at the American Society of Human Genetics Meeting 2016, Vancouver. Meeting Abstract book p. 1301. Free access.

8. Biomarin R&D Day 2017 presentation.

9. Biomarin press release. BioMarin Announces Fourth Quarter and Full Year 2017 Financial Results.

10. Therachon Feb 14, 2018.Therachon Announces Dosing of First Subject in Phase 1 Clinical Trial Evaluating TA-46, a Novel Investigational Therapy for the Potential Treatment of Achondroplasia.

11. Ascendis Pharma. TransCon-CNP.

12. 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.

13. FiercePharma Jan 30, 2018. BridgeBio’s QED Therapeutics picks up discarded Novartis cancer drug.

Treating achondroplasia: news about BMN-111

Today, the Australian program 60 minutes has released a video with an interview with Dr. Ravi Savarayan and showing his work in the phase 2 study with BMN-111. Here goes the link:

My opinion? This is another sign that the therapy is being successful. We still have to wait for the complete study results to be released in next June to have a better picture.

Treating achondroplasia: just one's right

Introduction

Everyday is a day to learn something new. As my interest for achondroplasia grows stronger, I have joined a small number of groups related to this genetic condition in Facebook, where I keep learning a lot.These groups, most of the time hosting very rich discussions or simply the sharing of experiences of parents or individuals with restricted growth conditions, in which wisdom is prevalent, also witness harsh debates regarding current (surgical) and potential (drugs in investigation) therapies for achondroplasia. Nevertheless, while sincere comments and questions such as why should we treat something that is normal? or she (the kid) is perfect as she is, a gift of God are common, sometimes we can also see others full of rage, bearing prejudiced thoughts like do you want to extinguish the race?  (the person who expressed this thought was referring to a "dwarf race") Believe me, this one I read this week and is the one which motivated me to publish this text.

It is about who we are

There is just one race, the human race. With all its presentation package diversity. Very, very frequently, the package is not perfect, but the imperfections come in a wide range of severity levels. Sometimes it is just a hemangioma in the skin, or a bad vision, because the eye lens is distorted and you cannot see far away (myopia). Rarely, the imperfection is so severe that it is not compatible with life, like in anencephaly. In other cases, the imperfections will appear later in life (and they are also extremely common).

Humans have been evolving and learning how to deal, manage, treat and more and more, cure these imperfections. Long time ago, glasses have been invented to correct some of the eye issues (Figure 1) and magnification was the great tool for Galileo to develop his heliocentric theory. But now, not only there are millions of fashionable glasses and the Hubble, but also to treat (and cure) myopia and other eye conditions, corrective surgery is often available. Or you can just drip drops in your eyes to treat your glaucoma.

Figure 1. Glasses in the XV Century. (from Wikipedia)

What could someone say to an individual that defines inventions or innovations or solutions aiming the human well being (in this particular case, achondroplasia) as a threat to the race?

In the last century, strong and respectable organizations have grown defending social rights and have been fighting hard to improve the life of individuals affected by genetic conditions that lead to growth restriction. They came together with the raise of other social organizations which defend other minorities' rights.  These organizations have been fighting a long fight to establish benefits for those that have to handle more challenges in the daily life. It took many decades for Americans of African origin to gain the same social rights other Americans had. Society now has more awareness about the diversity of the human race. 

So, when someone comes and says that therapies for dwarfism are a threat to the race, something is really wrong. This kind of argument goes against all that has been achieved by these renowned organizations.

The state of Health

One year ago, thinking about those debates about why should we treat achondroplasia or any other condition or disease that brings suffering to the individual affected, I have published the following text in the Achondroplasia group in Facebook. Suffering here means any kind of challenge one may face in an unbalanced manner, in a way that someone who is not affected by that condition would not. 

There has been a lot of controversy around therapeutic options for achondroplasia and other types of dwarfism lately. The target today are surgical interventions such as limb lengthening, which is a feasible option to those who decide for it.

Limb lengthening would not eliminate a gene mutation. So, this would not be the case of vanishing the human diversity. It would also not correct all medical issues that may occur in someone with achondroplasia. However, it may correct some of them, such as the lumbar lordosis that may worsen the common spinal stenosis and the common varu legs, which also are cause of undue pressure on knees, with known consequences, among other medical benefits.

In the context of publicly charging against those who decide to go for these surgical interventions, social and psychological aspects have been also frequently underestimated and are put together with the cosmetic aspect to reduce their relevance.

The state of Health is more than just not being ill, as has been defined almost 70 years ago by the World Health Organization: 

"Health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity."

It is an individual right to decide or not for a path or another. For example: one can decide if he/she will have a surgery for myopia or continue to use glasses. One can decide to have breast prosthesis implanted after a surgery for breast cancer. One can argue that both above procedures are cosmetic in first place, but in fact they are targeting needs that go beyond the mere physical state of health. 

One may not agree with a decision by another individual, and this is also one's right. But why does one fight so hard against something that may bring many benefits (real or imagined) for the other? 

Therapies for achondroplasia and other forms of dwarfism will be a reality in the next decade and this is good. 

Today, the quest is surgery. Tomorrow, it may become a pharmacological therapy. Both approaches may be understood as aiming one goal only: to improve the Health of the individual, in the broad terms of the WHO definition.

Think about it.

El blog Treating Achondroplasia: Tercer Año en la Red

Traducción al Español: María Cristina Terceros S. (MaCriTeS)

En estos días, en el mes de enero, el blog está cumpliendo sus tres años de edad. Cuando lo inicié, mi plan era revisar la biología de la acondroplasia, e indicar las terapias en potencial que estaban siendo investigadas hasta aquel momento. Hay un significativo número de investigadores en todo el mundo trabajando con esta displasia ósea, con revisiones brillantes que están siendo publicadas todos los años en la literatura especializada, y yo no tenía la intención de apenas reproducir sus trabajos, ya que no estaba involucrado en la investigación básica de la acondroplasia, ni tampoco compartía sus experiencias clínicas.

Un punto de vista personal

Como médico, he visto a pacientes por casi 30 años, y realmente creo en la relación médico-paciente como una herramienta para una mejor atención a salud. También creo que cuanto más uno sabe sobre un determinado problema, mejor (o más inteligentemente, o más fuertemente) uno puede luchar contra él (sí, es verdad, hay excepciones). Para mí, apenas dar un diagnóstico correcto y prescribir el tratamiento indicado, nunca fue suficiente.

Un gran desafío para los médicos es garantizar que sus pacientes con condiciones crónicas, como diabetes, hipertensión, asma, harán el tratamiento correcto a un largo plazo, lo que nosotros llamamos: adhesión a la terapia. Los medicamentos actuales para tratar estas condiciones crónicas son altamente eficaces, pero no llevan a la cura, a la sanidad total; en muchos casos el tratamiento debe ser continuo.

Así, a lo largo de los años, creyendo que más conocimiento sobre las enfermedades podría ayudar a los pacientes a administrar mejor sus tratamientos, he insertado orientaciones sobre biología, fisiopatología, farmacología, durante sus consultas. Hago uso de ilustraciones, modelos de plástico que reproducen la anatomía, dibujos, esponjas para mostrar qué es lo que está sucediendo con el paciente. Comprender el problema puede ayudarlo(a) a realmente hacer la terapia para su propio bien. Aprendí que, en muchos casos, eso se convierte en una verdad y me siento feliz.

¿Por qué el blog?

Y todo esto, ¿qué tiene que ver con la acondroplasia? Cuando comencé a estudiar la acondroplasia hace casi siete años, al poco tiempo me di cuenta de que el lenguaje en los textos científicos era complejo, y pensé en los pacientes en mi consultorio. Como mi interés con relación a la acondroplasia iba más allá del campo profesional, pensé, ¿qué podría hacer para compartir el conocimiento que estaba reuniendo con aquéllos a quienes yo quería ayudar? Las explicaciones necesarias se encontraban en el idioma del mundo real. Y fue de esa manera que surgieron los primeros textos, como lo que compartí en una antigua lista de correo electrónico sobre acondroplasia el año 2010.

El blog comenzó como una extensión de ese pensamiento. No podía simplemente mantener el conocimiento acumulado guardado. FGFR3, placa de crecimiento, condrocitos, CNP, enzimas, quinasa, mutación, etc. ¿Cómo colocar toda esa información de una forma que pudiera tener sentido para los “no iniciados”? Era el año de 2012, y después de haber conocido a Carmen Alonso, de la Fundación Alpe y a los Haider, de la iniciativa Growing Stronger, vi cómo podría hacer eso y decidí comenzar el blog.

Es eso. El blog intenta reunir informaciones dispersas entre los estudios publicados de una manera más simplificada, usando imágenes o ilustraciones del mundo real para ayudar a los lectores interesados a comprender la ciencia de la acondroplasia.

El blog hasta este momento ha llegado a 81 mil visitas de más de 120 países. Agradezco a cada una de las personas por su interés en los temas discutidos aquí, y espero que el blog les haya sido de utilidad.

Nada para hacer, mucho para hacer

Otro aspecto de ser médico, es que es difícil no disponer de una solución para un paciente, permanecer impotente ante un diagnóstico. Esto se traduce en el contenido del blog, bajo el formato de una perspectiva de mirar hacia adelante.

En la actualidad, no existe un tratamiento establecido para la acondroplasia, si bien existan muchas terapias en potencial en diferentes niveles de desarrollo, desde una pequeña luz en la mente, una idea, un compuesto patentado, al primer medicamento actualmente ya en ensayo clínico. El blog explora, sin ningún tipo de prejuicio, todas las potenciales terapias divulgadas en la literatura, intentando dar una visión equilibrada sobre ellas.

Hubo un tiempo en que personas con trastornos del crecimiento mal tenían el reconocimiento por la sociedad como seres humanos, cuando los derechos sociales eran una fantasía, y fuertes asociaciones fueron creadas para luchar por ellas, como la LPA y la Fundación Alpe. Con estas asociaciones, la comunidad fue testigo de victorias y logros, aunque todavía queda mucho por hacer.

Sin embargo, hoy personas que son afectadas por condiciones que menoscaben el crecimiento o simplemente involucradas, están siendo testigos de la alborada de una nueva era, donde las soluciones están surgiendo para tratar diferentes disturbios de crecimiento, incluyendo la acondroplasia. Este cambio lleva a la necesidad de una renovación inteligente de la mentalidad entre los líderes de la comunidad interesada, y aquellos que influyen en las decisiones, que tendrán que comenzar a pensar no solamente en los que están vivos, sino también en las nuevas generaciones que están por llegar.

De esta manera, hay mucho para hacer. Desde aprender más sobre la condición hasta la forma cómo la investigación es realizada, los temas económicos, las dificultades y los desafíos. Existen más de 7 mil enfermedades raras ya descritas, la mayoría de ellas afectando a pocas personas, la mayoría niños. Solas, estas personas tienen poca fuerza para luchar. Sin embargo, junta, unida, la comunidad de enfermedades raras llega a ser de millones. En conjunto, las soluciones vendrán más rápido.

Como dijo Goethe:

"Saber no es suficiente, es necesario aplicar. Querer no es suficiente, es necesario actuar."

¿Qué podemos hacer para aumentar la investigación en las soluciones para la acondroplasia y los otros miles y miles de enfermedades raras? ¿Cómo podemos convencer a los inversores y a los pagadores de que el trabajo para mejorar la calidad de vida de las personas con enfermedades raras también irá a mejorar la calidad de vida de la sociedad en su conjunto?

Existen muchas iniciativas en curso. ¿Qué tal tener un papel más activo en la transformación de nuestra sociedad? Tú te puedes convertir en parte de la(s) solución/ soluciones. Es por eso que iniciativas como la del Día de las Enfermedades Raras son tan importantes.

Feliz 2015!

O Blog Tratando a Acondroplasia: Terceiro Ano na Rede

Agora em janeiro, o blog está chegando aos três anos de idade. Quando o comecei, o plano era rever a biologia da acondroplasia e apontar as potenciais terapias que estavam sendo exploradas até aquele momento. Há um número significativo de pesquisadores em todo o mundo trabalhando com esta displasia óssea, com brilhantes revisões sendo publicadas todos os anos na literatura especializada, e eu não tinha intenção de apenas reproduzir seus trabalhos, já que não estava envolvido na pesquisa básica da acondroplasia, nem compartilhava de suas experiências clínicas.

Um ponto de vista pessoal

Como médico, tenho visto pacientes por quase 30 anos e realmente acredito na relação médico-paciente como uma ferramenta para um melhor atendimento. Também acredito que quanto mais você sabe sobre um problema melhor (ou mais inteligentemente, ou mais fortemente), você pode lutar contra ele (sim, há exceções). Para mim, apenas fazer o diagnóstico certo e prescrever o tratamento correto nunca foi suficiente.

Um grande desafio para os médicos é garantir que seus pacientes com condições crônicas, como diabetes, hipertensão, asma, farão o tratamento corretamente em longo prazo, o que chamamos de adesão à terapia. Os medicamentos atuais para tratar estas condições crônicas são altamente eficazes mas não levam à cura, em muitos casos o tratamento deve ser contínuo.

Assim, ao longo dos anos, acreditando que mais conhecimento sobre suas doenças poderia ajudar os pacientes a gerir melhor seus tratamentos, tenho inserido orientações sobre biologia, fisiopatologia, farmacologia, durante as consultas. Uso ilustrações, modelos de plástico que reproduzem a anatomia, desenhos, esponjas para mostrar o que está acontecendo com o paciente. Compreender o problema pode ajudá-la(o) a realmente fazer a terapia para seu próprio bem. Aprendi que, em muitos casos, isso se torna verdade e me sinto feliz com isso.

Por que o blog?

O que isso tudo tem a ver com a acondroplasia? Quando comecei a estudar a acondroplasia quase sete anos atrás, logo percebi que a linguagem nos textos científicos era complexa e lembrei dos pacientes em meu consultório. Como meu interesse na acondroplasia ia além do campo profissional pensei no que poderia fazer para compartilhar o conhecimento que eu estava reunindo com aqueles que eu queria ajudar? A chave estava no idioma do mundo real. E foi assim que os primeiros textos começaram, como o que compartilhei em uma antiga lista de correio eletrônico sobre acondroplasia em 2010.

O blog começou como uma extensão desse pensamento. Não podia simplesmente manter o conhecimento acumulado guardado. FGFR3, placa de crescimento, condrócitos, CNP, enzimas, quinase, mutação etc., como colocar toda essa informação de uma forma que poderia fazer sentido aos não "iniciados"? Era 2012, e depois de conhecer Carmen Alonso, da Fundación Alpe, e os Haiders, da iniciativa Growing Stronger, vi como poderia fazer isso e decidi começar o blog.

É isso. O blog tenta reunir informações espalhadas entre os estudos publicados de uma forma mais simplificada, usando imagens ou ilustrações do mundo real para ajudar os leitores interessados a compreender a ciência da acondroplasia.

O blog chegou a 81 mil visitas de mais de 120 países. Agradeço-lhe por seu interesse nos temas discutidos aqui e espero que o blog esteja sendo útil para você.

Nada a fazer, muito o que fazer

Outro aspecto de ser um médico, é que é difícil não dispor de uma solução para um paciente, estar impotente diante de um diagnóstico. Isso se traduz no conteúdo do blog, sob a forma de uma perspectiva de olhar à frente.

Atualmente, não há tratamento estabelecido para a acondroplasia, embora haja muitas potenciais terapias em vários níveis de desenvolvimento, desde um lampejo na mente, uma idéia, um composto patenteado, ao primeiro medicamento já em ensaio clínico. O blog explora, sem preconceito, todas as terapias potenciais divulgadas na literatura, tentando dar uma visão equilibrada sobre elas.

Houve um tempo em que pessoas com desordens do crescimento mal eram reconhecidas pela sociedade como seres humanos, quando os direitos sociais eram uma fantasia, e fortes associações foram criadas para lutar por elas, como a Little People of America e a Fundación Alpe. Com essas associações, a comunidade testemunhou vitórias e conquistas no campo social, embora haja muito a fazer ainda. 

Nos últimos anos, no entanto, pessoas que são afetadas por condições clínicas que afetam o crescimento ou que simplesmente estão envolvidas no meio vêm percebendo o alvorecer de uma nova era, em que soluções estão surgindo para tratar vários distúrbios do crescimento, incluindo a acondroplasia. Essa mudança leva à necessidade de uma renovação inteligente do modo de pensar entre os líderes da comunidade interessada e outros tomadores de decisão, que terão de começar a refletir não só sobre os que estão vivos, mas também sobre as novas gerações que estão chegando.

Assim, há muito o que fazer. Desde aprender mais sobre a condição genética à forma como a pesquisa é realizada, as questões econômicas, as dificuldades e desafios. Há mais de 7 mil doenças raras descritas, a maior parte delas afetando poucas pessoas, a maioria crianças. Sozinhas, elas têm pouca força para lutar. Juntas, no entanto, a comunidade das doenças raras chega aos milhões. Em conjunto, as soluções virão mais rápido.

Como Goethe disse:

"Saber não é suficiente, é preciso aplicar. Querer não é o suficiente. É preciso agir."

O que podemos fazer para aumentar a investigação de soluções para a acondroplasia e os milhares de doenças raras? Como podemos convencer os investidores e os pagadores que o trabalho para melhorar a qualidade de vida das pessoas com doenças raras também irá melhorar a qualidade de vida da sociedade como um todo?

Há muitas iniciativas em curso. Que tal ter um papel mais ativo na transformação da nossa sociedade? Você pode se tornar parte da(s) solução(ões). É por isso que iniciativas como a do Dia das Doenças Raras são tão importantes.

Um feliz 2015 !

The Treating Achondroplasia Blog: Third Year Online

The blog is reaching three years this January. When I started it, the plan was to review the biology of achondroplasia and point out the potential therapies that were being explored so far. There is a significant number of researchers around the world reviewing this skeletal dysplasia, with brilliant reviews being published every year in the specialized literature and I had no intention to just reproduce their work, since I was not involved in the basic research of achondroplasia, and I didn't share their clinical expertise.

A personal point-of-view

As a practicing physician, I have been seeing patients for almost 30 years and I truly believe in the doctor-patient relationship as a tool for better care. I also believe that the more you know about a problem the better (or smarter, or stronger) you could fight it (yes, there are exceptions). For me, just making the right diagnosis and prescribing the right treatment has never been enough.

One major challenge for doctors is to make sure their patients with chronic conditions, such as diabetes, hypertension, asthma, will take the treatment correctly in the long term, what we call adherence to therapy. Current medicines to treat these chronic conditions are highly effective but don't grant the cure, the therapy must be continuous in many cases.

So, over the years, believing that more knowledge about their diseases could help patients to better manage their treatments, I have been inserting pieces of biology, pathophysiology, pharmacology, during the appointments. I use illustrations, plastic models reproducing the anatomy, sponges to show what's going on with the patient. Understanding the problem might help him or her to really engage in the therapy for their own good. I learned that in many cases this turns to be true and I feel happy about it.

Why the blog ?

What does this all have with achondroplasia? When I started to study achondroplasia almost seven years ago, I soon realized that the language in the scientific texts was complex and I thought on the patients in my office. Since my interest in achondroplasia went beyond the professional field I thought what I could do to share the knowledge I was gaining to those I wanted to help? The explanations needed to be in the real world language. And that's how the first texts started, like the one I shared in an old achondroplasia mail list back in 2010.

The blog started as an extension to that thought. I couldn't just keep the knowledge accumulated hidden. FGFR3, growth plate, chondrocyte, CNP, enzymes, quinase, mutation, etc. how to put all that information in a way that those not "initiated" could make sense of them? It was 2012 and after meeting Carmen Alonso, from Fundación Alpe, and the Haiders, from the Growing Stronger initiative, I saw how I could do it and I decided to start the blog.

That's it. The blog tries to bring together information split across the published studies in a more simplified way, using images or illustrations of the real world to help interested readers to understand the science of achondroplasia. 

The blog has reached 81000 visits from more than 120 countries. I thank you for your interest in the topics discussed here and I hope the blog has been useful for you.

Nothing to do, a lot to do

Another aspect of being a doctor, is that it is hard to not having a solution for a patient, to being impotent in face of a diagnosis. This translates in the blog's content in the form of a looking forward perspective. 

Currently, there is no established therapy for achondroplasia, although there are many in several levels of development, from a spark in the mind, an idea, a patented compound, to the first one already in clinical trial. The blog explores,without prejudice, all potential therapies disclosed in the literature, trying to give a balanced view of them. 

There was a time when people with growth disorders were hardly recognized in society as human beings, when social rights were a fantasy, and strong associations were built to fight for them, such as LPA and Fundación Alpe. We have witnessing triumphs and victories although much is still to be done.

Nevertheless, now people who are affected by growth conditions or simply involved are observing the dawn of a new era when solutions are coming to treat many growth disorders, including achondroplasia. This will need a smart change of mindsets for the community leaders and stakeholders, who will need to start thinking not only in the living but also in the new generations coming.

So, there is a lot to do. From learning more about the genetic condition to how the research is carried out, the economics, the caveats and challenges. There are more than seven thousand rare diseases described, most of them affecting very few people, the majority children. Alone, they have poor strength to fight. Together, however, the rare disease community reaches the millions. Together, solutions will come faster.

As Goethe said:

"Knowing is not enough; we must apply. Willing is not enough; we must do."

What can we do to increase the research towards solutions for achondroplasia and the thousands of rare conditions? How can we convince investors and payers that working to improve the quality of life of people with rare conditions will also improve the quality of life of the society as a whole?

There are many initiatives ongoing. What about having a more active role in the transformation of our society? You can become part of the solution (s). That's why initiatives such as of the Rare Disease Day are so important. 

A happy 2015 for you!