Thursday, February 23, 2012

The BMN-111 post

Looking back at my stats, I just realized that I only posted ONCE in ALL of 2011. Holy cow, that's neglect. What can I say - 2011 was a busy year. Those of you who are friends on Facebook may have noticed the number of countries I've been to in the last 6 months. It's fun, but contributes to the "super serious blog slacking" :-)

Anyway, I've been getting more intensely involved in LPA affairs lately, and one of the things I've been learning about is the medical research that is focusing on therapeutic treatments for achondroplasia. Obviously that's something I'm very interested in following, since my daughter has achon, as do several of my close friends and their children. One major benefit to this involvement has been the chance to get a lot of information on the current state of such research; I was recently present during a detailed presentation by medical professionals on the new drug BMN-111 which BioMarin is currently bringing to clinical trials.

Earlier this evening, a mom posted on the Facebook POLP page asking if anybody knew anything about BMN-111. I started off posting a comment and wound up writing a term paper. There was enough information there that I thought it might be helpful to repost here as well. So, here's what I know.

There is a lot of medical research being done right now, trying to find a way to encourage the bone growth that is being restricted by the FGFR3 gene. BMN-111 is the first to get close to making it to market. Basically what happens is there is a receptor inside the cells that is supposed to turn on and off to regulate growth. With the FGFR3 mutation that causes achondroplasia, that receptor is stuck in the ON position which causes bone growth to happen in quick spurts rather than slow ones, which has the end result of causing the bone to not grow properly. What BMN-111 is attempting to do is to "dim" the output of that receptor to about 50%, trying to replicate the growth signal in a "typical" cell, as in an AH individual. 
The drug has been tested and proven effective in mice models so far, re-invigorating growth that is slowed by achondroplasia. The next steps are human trials. Phase 1 is testing in healthy average height adults to see if any negative side effects can be identified. Phase 2 will involve testing in children with achondroplasia.

What we do know is this: it does not eliminate the gene for achondroplasia. A person being treated with BMN-111 still has the gene mutation which still has the potential to be passed on to the next generation. What it does in mice models is to eliminate the shortened limbs, tightened foramens, and recessive midface caused by the FGFR3 mutation. Theoretically, this means it would eliminate the need for decompression surgery both early and late in life, as well as surgeries to correct obstructive sleep apnea (tonsillectomy/adenoidectomy for the purposes of opening up the airway, etc). It would also have the end result of increasing the patient's final height. Assuming, of course, that it works in humans the same as it does in mice. We also know that it will only work in patients whose growth plates haven't closed yet. In girls, this usually happens around a year after the first menses; in boys a few years later. 
What we don't know is this: first, whether it will actually work in humans the same as it does in mice. Second, whether there will be any side effects. Hopefully Phase 1 of testing will clear that up, but we'll see. Third, we don't know what it will mean in terms of adult height for children who receive the treatment, largely because the drug hasn't been out long enough for any longitudinal studies, also because it's really hard to predict human growth from a mouse model.

We were approached about a month or so ago about having Caitlin participate in the phase 2 trials. After a lot of discussion, we've decided not to have her participate for now, since there really is no information regarding potential negative side effects, and her symptoms aren't severe enough for us to feel comfortable taking the risks. Other people's situations may be different, or they may have different perspectives - we'll see. There's definitely a lot to think about with this...

Anyway, that's what I know. If anybody has any questions, please feel free to ask, either on FB or here in the comments. I'll answer what I know, and what I don't know I can probably find out through the channels I have access to.

Hope this helps some of y'all to make your decisions!

UPDATE: 12/26/12

Some great friends of ours just posted their opinion on BMN-111 on their own blog. It's great to read this from the perspective of a pair of adults with dwarfism - Go forth and get educated!!


Caden and Mommy said...

Thanks Mike! Dan and I had discussed this ... and wondered about how it would effect the LP features, as in the recessive midface. We knew obviously it made the bones grow "longer", but had wondered about the other "aspects". All good info provided ... and I think you and Cheryl made the right decision for Caitlin :o)

Emily Camenga said...

Thank you for this post...I was really curious when I heard the press release but there was no info to be found! Thanks for the great information.

Anonymous said...

You should consider enrolling Caitlin into the observational study that will allow for the natural history of achondroplasia to be better understood. ( This helps as a control for when the Phase 2 study starts with kids on drug.

rie nakada said...


I'm Rie Nakata.
I live in Japan.

I have a daughter of achondroplasia.
It is two months old.

I found your blog If you are looking at a BMN-111.
I'm not good at English.
Includes the use of the blog, do not know yet.
I'm sorry there was rude.

I want to participate in the Phase 2 study.
How do you have to be registered?
Would you please tell me

I'm waiting for a reply from you.
Thank you.