Beyond Achondroplasia

Growing together with Clara

Potential treatments for achondroplasia

In this synopsis of the current achondroplasia potential treatments, you will find that, at this point (August 2015) there are three drugs that will potentially reduce with expected significance the anatomic effects of achondroplasia produced by the aberrant FGFR3 activity in the growth plate of long bones:

1- BMN-111 – a CPN analogue from BioMarin´s pharmaceutical, under evaluation in a clinical trial, now at phase 2, a cohort dose-escalating study.

2- Soluble FGFR3 – a solution by TherAchon, a spin-off of the Inserm lab, France. Still without starting the preclinical development of the soluble FGFR3.

3-Meclizine – it´s an anti-histaminic used to treat vertigo and motion sickness and also a drug with repositioning purpose, under study for a new therapeutic indication for achondroplasia.  The Japanese team has to test if its be safe and efficient in the tested doses. Advantages: It is already available worldwide, it´s cheap and it´s of oral administration.

Many other drugs had some potential but for one or other reason were left aside:

1- GH (Growth hormone)- doesn´t work in achondroplasia, showing just irrelevant changes in height.

2- PTH analogue – Teriparatide – with high risks. Lifelong high dose exposure to teriparatide developed osteosarcomas and other kinds of bone cancer.

3- NC-2 – most probably, the interest in this molecule for further studies by a pharmaceutical is over (before it really began)

4- Vessel dilator – with no lab animal evaluation for the hypothesis of achondroplasia treatment

5- NF449 – FGFR3 tyrosine kinase inhibitor in a very initial research phase

6- A31 – another anti-FGFR3 tyrosine kinase inhibitor that induces a large decrease in the FGFR3 expression in mutant femurs

7- Aptamers – not under research for achondroplasia

8- iRNA – in this case, a possible future approach of genetics in achondroplasia,  that could cut the mRNA with the information to produce mutated FGFR3.

9- Statins – Another repositioning drug. It´s a class of drugs renown for their action against cholesterol and investigated because they have anabolic and protective effects on chondrocytes. The research group tested an injection of 1 mg per kg of rosuvastatin into the ACH mouse model that restored bone growth in the limbs and head. However, statins, as they are, can´t be used in children once they interfere with the production of cholesterol, a lipid molecule (fat) and absolutely essential for young children natural and physiologic development.

“Cholesterol is an essential structural component of all animal (not plant or bacterial) cell membranes that is required to maintain both membrane structural integrity and fluidity. Cholesterol enables animal cells to not need a cell wall (like plants and bacteria) to protect membrane integrity/cell-viability, able to change shape and move about (unlike bacteria and plant cells which are restricted by their cell walls).

In addition to its importance within cells, cholesterol also serves as a precursor for the biosynthesis of steroid hormones (the first step in the chain that originates glucocorticoids,mineralocorticoids as also androgens, estrogens, and progestogens), bile acids, and vitamin D. 

Cholesterol is the principal sterol (an organic alcohol) synthesized by animals. All kinds of cells in animals can produce it. In vertebrates (as humans) the hepatic cells (liver cells) typically produce greater amounts than other cells. It is almost completely absent among prokaryotes (bacteria and archaea).

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