Saturday, June 30, 2012

Challenges for the treatment of achondroplasia: to boldly go where no man has gone before

What does the famous Star Trek quote have with drug research?

Drug discovery is not easy. It takes a lot of effort of brilliant minds and huge investment to make a chemical molecule to become a medicine. The path the potential new drug must take, recently reviewed in this blog, is hard.

We have been discussing the main drivers for drug development, such as the high prevalence of the condition, its social appeal or the severity of the disease. In the last two articles, we have also briefly reviewed the main challenges for a drug before it reaches the drugstore. However, there are other hurdles in this path. Another barrier for drug development is the amount of knowledge already available about the target condition. Let's talk a bit about this and I will try to explain what it does have with the title of this article.

GPS takes you everywhere

Today, when driving far away from home, how many people would turn off the GPS and rely on a paper map or, even worse, only on instincts, to reach point B departing from point A? I guess a minority would try the ‘adventure’ of exploring an unknown road, crossing unfamiliar towns, without the GPS or a map. It is human to seek safety, and maps and GPS are tools that increase confidence or the feeling of safety.

This piece of thought you can extrapolate for any area of life. How many people will bet their economies in the stock market, which is very unpredictable, against putting the savings in a retirement fund with clear rules about where to invest the money? Or, let´s see within the pharmaceutical industry, where is most of the investment engaged? Look at the trends and you will find that the main pharma research is in areas where the disease mechanisms are already well known (Berggren, 2012). From diabetes and hypertension to cancer, the chemical pathways have been broadly charted. In other words, the research is directed to areas where there are already good maps, where there is a good GPS coverage.

Why is that so? It is so, because it is less risky. A molecule designed to tackle a known metabolic pathway is more likely to succeed in terms of becoming a drug than one designed to interfere in a roughly known chemical reaction. This also means more chance of return of investment with less effort. Take a look in the drugstore: how many different medicines from the same classes are currently available to treat hypertension (try angiotensin converting-enzyme blockers or beta-blockers or diuretics in this link)?

As the risk is greater, there are comparatively few initiatives in uncharted territories, either because of the rarity of the condition or just because no one has been there before.

No pain, no gain

I have little patience with scientists who take a board of wood, look for the thinnest part and drill a great number of holes where drilling is easy.

Albert Einstein
(in Bite-size Einstein. Mayer J & Holmes JP. St. Martin’s Press, New York. 996. p 62.)

Going ahead into the unknown is difficult. You, the scientist, the investigator, have less information about it, people around will start to question your decision, investors will be more cautious before giving you resources to explore the territory. And then, if the first results of you research do not seem too good, things will become even harder. This is common thing among scientists and has been already dramatized (have you ever watched Extraordinary measures?).

Exploring the uncommon

In general, rare conditions like achondroplasia fall under this human pattern of looking for the safer and easier paths. Achondroplasia is rare, but it is not exactly uncharted. On the contrary, most of the mechanisms that cause the bone growth arrest is already known. So, what is preventing the scientific community to present therapeutic options for achondroplasia? Well, what prevents more research in achondroplasia is exactly the lack of resources to put investigators in the lab, working on objective questions, working on solutions.

Public funding is not enough: governments have been facing increasing health costs burden (1) and tend to direct grants and sponsorship to what is considered main public health problems (which is fair, in terms of collectivity). Achondroplasia (and many other rare conditions) is not among the main public health targets. And, interestingly, public funding for basic research not always means the development of a new drug in the future. (2)

At the same time, as I have mentioned above, the private based research is concerned about the costs of drug discovery and the risks related to the uncommon. To reduce these feared risks, several big pharma industries have been signing agreements with academic institutions or small biotechnology companies. In a simple way to say, they are intended to be a kind of risk-sharing partnership for drug discovery. (3)

However, in a context of a rare clinical condition where the population to be treated is composed by children, where there potential risks are deemed greater, it´s under the coverage of organized initiatives that new strategies can be developed. Parents’ initiatives have been contributing very much for the discovery of new strategies for the treatment of rare conditions. One good example of these initiatives is given by the Cystic Fibrosis Foundation.

Parents need to decide if they will keep waiting and copying with what was uncorrectable in the past, or if they will directly become involved in the next steps of the drug discovery. There are several potential strategies to treat achondroplasia waiting to be explored. They are brand new, they are like uncharted territories. I invite you to learn about Growing Stronger, a Parents’ initiative working to accelerate the research for solutions to improve the health of children affected by achondroplasia.

Many of the great mankind achievements have been consequence of someone deciding to cross the line. Victory is made of hard work and courage to advance beyond the common knowledge, to find the solution hidden behind the easy formula, to surpass the charted territory, to boldly go where no man has gone before.


1Morris H. U.S. Health Care Costs More Than ‘Socialized’ European Medicine.  The New York Times, 28 Jun 2012.

2. Margaret E. Blume-Kohout. Does targeted, disease-specific public research funding influence pharmaceutical innovation? J Pol Anal Manag 2012; 31 (3): 641–60.

3. Mullard A. 2011 in reflection. Nat Rev Drug Discovery 2012; 11: 6-8. doi:10.1038/nrd3643.

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