Beyond Achondroplasia

Growing together with Clara

Statins for achondroplasia?

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Nature journal published yesterday an article connecting statins to achondroplasia treatment. You can read the abstract of the article

Statin treatment rescues FGFR3 skeletal dysplasia phenotypes“.A. Yamashita et al. Nature,doi:10.1038/nature13775, 2014

Statins or HMG-CoA reductase inhibitors are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA redutase, which plays a central role in the production of cholesterol in the liver, which produces about 70 percent of total cholesterol in the body.

Cholesterol is not a demon. It is necessary for normal embryonic development and has important functions both before and after birth. It is a structural component of cell membranes and the protective substance covering nerve cells (myelin). And cholesterol is plays an important role in the production of sexual hormones and digestive acids.

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Image taken from: “The interplay between circadian system, cholesterol synthesis, and steroidogenesis affects various aspects of female reproduction” Frontiers in endocronology journal

Here you can read a very interesting article about how important it is cholesterol.

The rare disease Smith-Lemli-Opitz syndrome is caused by a mutation in the DHCR7 gene, which provides instructions for making an enzyme 7-dehydrocholesterol reductase, responsible for the final step in the production of cholesterol.

Well, in this new discovery about the use of statins in achondroplasia, many is being discussed by now.

An article at the “The Scientist” webjournal has a critical approach to the new article release, with of opinions of major personalities around achondroplasia research and medical society.

“The researchers identified the cholesterol-lowering drug’s growth-stimulating properties during a screen using induced pluripotent stem cells (iPSCs) derived from patients’ skin cells that were differentiated into cartilage-producing cells called chondrocytes. The patients had the most common form of dwarfism, achondroplasia, as well as a rarer disorder, called thanatophoric dysplasia type 1 (TD1), which is typically fatal early in life.

They definitely show that the cellular model is really working and it’s very interesting to have that,” said Elvire Gouze, who studies achondroplasia at the French Institute of Health and Medical Research (INSERM). Gouze said she is interested in using the model in her own research going forward.

The study is “a wonderful proof of principle that statins may ameliorate . . . the mutant FGFR3 hypersignaling,” said Andrea Superti-Furga, a pediatrician who studies genetic skeletal diseases at the University of Lausanne in Switzerland. “Having that said that, there’s a lot of questions raised by this paper.”

Still, many questions must be answered before statins are tried out in human children with dwarfism. INSERM’s Laurence Legeai-Mallet noted that the bone growth observed in mice was not dramatic.It’s a very mild phenotype,” she said. “They did not observe a strong effect.”

And Gouze noted that both the wild-type and mutant mice varied in size; the smallest mutant mouse in the study was larger than the smallest wild-type mouse.

It’s still unclear whether statins are safe for use in young children.

But while statins have been shown to be safe for adults and have even been used in some older children with cholesterol disorders, there is no data on its safety for babies. One concern is that cholesterol itself is key for building cells membranes and particularly for brain development in developing children.

“Before moving to clinical tests, safety and efficacy of statins for FGFR3 chondrodysplasia need to be tested in animal models extensively,” said Tsumaki”

“And at the same time, Prof. Tsumaki is cautious about these findings, especially with regards to children. “Currently, statins should not be used in children, because statins decrease cholesterol, an essential steroid for the growth and development of children“. He adds that further examination is also needed on the appropriate delivery and dose for skeletal dysplasia treatment. “We show that an injection of 1 mg per kg of rosuvastatin into the ACH mouse model restored bone growth in the limbs and head. However, this dose would translate into 70 mg per day for a 70 kg human, which far exceeds the 20 mg limit in Japan and 40 mg limit in Europe and the U.S

More about the used of statins in achondroplasia has to be studied before any more conclusions.

5 Comments

  1. it’s our new hope!i’m from China.thanks a lot!

    • Hello Arthur. It´s might work, but I need to do more research about the cellular mechanism and side effect for statins in young children. But is´t great to have good hopes!!! Hope to hear from you again.

      • Inês, thank you very much for your great work, I get lots of imformation from here. I have already introduced your blog to many chinese patients.In China, there are few research on ACH, those doctors only know how to diagnose who is a ACH patient.My e-mail:yashebuct@gmail.com. Best wishs to you and Clara. Arthur

  2. do you know of any studies being done on Hydrochondroplasia? we are in the seattle wa area.

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