In the present, achondroplasia has more opportunities in the scientific search for a treatment than almost any other rare disease has. And this is very amazing.
There are some relevant points in the science that is being produced for achondroplasia:
When thinking about diseases, conditions, disorders or syndromes, rare or frequent, a treatment is a way to manage it. Medical professionals use medication, therapy, surgery and other forms of treatments to help lessen the symptoms and effects of a disease. When a disease can’t be cured, doctors often use treatments to help control it.
On the other hand, a cure is the means to end a medical condition using a substance or procedure. It’s when the state of being healed or cured is reached, making the person free of the disease.
There is no cure in line for Achondroplasia now. This does not mean that it will not exist in the future. When? Well, it is impossible to predict.
I can visualize a probable cure in the future for achondroplasia, like changing the DNA or gene editing. A good candidate for this is the recent CRISPR technique. Reaching a cure by using gene editing is a great idea but the it would have to cut off the mutation in the chondrocytes and replace the vacant place left in the DNA with the correct genetic information. And this would have to be done during the embryonic stage of a baby with achondroplasia, meaning: shortly after the baby has been conceived. And this potential cure would have to be administered through the mother or directly in the embryo, still growing inside the womb.
This is, at this point, science fiction.
Achondroplasia is a rare condition that goes far beyond just a significant reduced height condition. Is a multisystemic condition: spinal stenosis- cervical or lumbar (the narrowing of the spinal canal that can compress the upper part of the spinal cord) that is associated with back pain, tingling and weakness in the legs that can cause difficulty with walking, sleep apnea, hydrocephalus, obesity, recurrent otitis media (ear infections), lordosis (sway of the lower back), kyphosis (front to back curvature of the spine), genu varum (bowed legs), joint pain, social problems.
The goal of a treatment for achondroplasia is to have a multisystemic effect.
The relevance of the word “potential”. At this point, there is no proof that one or more of the molecules/compounds under study now for achondroplasia will become a confirmed treatment for achondroplasia, meaning that it may not have beneficial effects with continuous efficacy and with reduced side effects, on short and long term. So, all the studies are now in the “potential box”.
On achondroplasia’s “potential treatments road” are the following disclosed research projects:
- Soluble FGFR3
- in parenthesis: (NVP-BGJ398 – the newcomer)
Falling aside of this road are:
- IPSCells are very interesting but are not in the Potential box. This can be important in testing new potential treatments for achondroplasia in clinical trials: an important step in developing a therapy for a given disease is understanding exactly how the disease works. To do this, researchers need to study the cells or tissues affected by the disease.
- The B-701 antibody, from BioClin Therapeutics, was announced to be in preclinical testing for achondroplasia, but with no further developments so far and no information about this type of antibody. But antibodies are very large molecules and it is virtually impossible for it to reach the growth plate.
- Statins are out of this race. They are inhibitors of a specific enzime, the HMG-CoA reductase, essencial to the production of cholesterol. Statins simply can not be used to treat children with achondroplasia since the main effect of this molecule is to reduce cholesterol levels and children absolutely need cholesterol for the normal body and physiological development: brain, nervous system, liver, production of sexual hormones and other body tissues. This inability to use statins for achondroplasia was even stated by Prof. Tsumaki, the head researcher of the study of statins for achondroplasia.
- Although there are studies coming mostly from Asia that are still pointing Growth Hormone (GH) as a treatment for achondroplasia, this molecule is out of this race. It is proved that the levels of growth hormone in children and adults with achondroplasia are within the normal range and the effects of GH in increasing height are just seen during the first year of administration and with significant side effects. GH does not work for achondroplasia.
What is still unknown about the potential treatments for achondroplasia at this stage?
In relation to BMN-111 there is still no information or knowledge about long term side effects or for how long will this potential treatment improve growth, or if it will reduce the most significant health complications related to achondroplasia.
About the soluble FGFR3, further results are needed and it is early for conclusions. The results in mice were very promising but there are still toxicity tests to be done and all the pre-clinical and clinical trials: phase 1, in healthy adults and phase 2, in children with achondroplasia.
Talking about meclizine, the researchers proved a reduction of the synchondroses fusion at the skull base level in mice (this improved the size of the skull base, meaning this could reduce the cervico-medullar stenosis) and shown an improvement in height also, but this is a molecule that has existed for more than 50 years and is already used to treat motion sickness in adults, in a punctual basis and is not prescribed for children. Toxicology studies are very important in this case.
Controversial point: Although meclizine is already available in the medicines market with indication for motion sickness in adults. At this point, meclizine is not eligible to be administered to children with achondroplasia, since there is no indication for its pediatric use in achondroplasia and further research and publications in this specific field have to be conducted.
About the NVP-BGJ398, it is a pan FGFR tyrosine kinase inhibitor (pan means “all”, so it isn’t specific for any of the receptors), an investigational compound of Novartis pharmaceutical company. At this moment, 4 clinical trials in Novartis on BGJ398 are being conducted for tumors. As stated by Novartis: “Efficacy and safety have not been established. There is no guarantee that BGJ398 will become commercially available”. There are many others FGFR tyrosine kinase inhibitors in study for several types of cancer. In association with Novartis researchers, Laurence Legeai-Mallet from INSERM, Université Paris Descartes, is conducting the research of this compound applied to achondroplasia.
But definitely, much more has to be studied about this compound, in particular if it can be further developed with specificity for FGFR3. There is no way an inhibitor that can interfere with the other receptors of this class (FGFR 1, FGFR2 and FGFR4), that have relevant actions in the natural development of the body of children with achondroplasia, can be used to treat this disease.
After all this, it is important to remember that there are several research teams worldwide involved and dedicated in studying treatments for achondroplasia. Without total assurance but with hope, the future of children with achondroplasia and their families can be brighter!