Saturday, April 30, 2011

Softball games begin

Today Arlington had her first softball game.
She insisted on posing several different ways before she left the game.
She kept saying "just one more!"  But I had to finally shoo her out the door.
She had a great first game.  Even after she had 1 1/2 hours of lacrosse this morning, she was ready to go for her game this afternoon.  I think she will sleep well tonight.
She hit the ball 3 times up to bat, and only got out once!  This is a big improvement from last year.  She has pretty good hand/eye coordination, and now that she is a bit older, it shows.
She scored 3 times as well.  She was pretty excited to tell me that they won the game when she got home.
And she got those white uniform pants nice and dirty, just like she should.  She is going to be a sports girl, I think.  Not dainty I am afraid.
She even got a chance to be the catcher.

She looks pretty hilarious with all of that stuff on.  But she likes wearing it.
So a good day.  After she got home from her game, she and her brother and sister played outside for an hour.  She is non-stop energy that girl.

Friday, April 29, 2011


Not that anyone ever cares when the mom of the family doesn't feel well, but I am going to tell you anyway.  I have an earache, a jaw ache and a sore throat.  (all together now.......awwwwwww).  I know of a walk in clinic that is open on Saturday, so I am going tomorrow to make sure that Cainan hasn't past his strep to me.  Poor me, I know.
I got up this morning at 5am like a crazy person and watched the Royal Wedding.  I was only 6 when Princess Diana got married, but always enjoyed watching repeats of her wedding.  She and I share a birthday.  She was killed the year I got married.  So - it was nice to watch the wedding today.  (like I know them personally, huh?)  The only bad part was that until about 5:50, I didn't see much - mostly it was waiting around and staring at the really odd hats the women chose to wear.  When Arlington got up, the first thing she wanted to see is the princess get married.  So, she got to see some of the ceremony before we had to leave for school.  And we watched the repeat this afternoon for a little while so she could catch what she missed.
Arlington informed me today that when she grows up she is going to move to England, marry Prince William's future child, and become a princess.  Sounds like a plan.

Thursday, April 28, 2011

Lebers Congenital Amaurosis (LCA) and RDH12

As many of you know, we have a "Feedjit" on the sidebar of our blog.  The nice thing about that is that I can see what has drawn many people to our blog (who have found us through Internet searches - not the people who already know us).

Lately, there have been many searches for RDH12 research and LCA information.  I am glad to see that our blog is a place people can come to learn a little bit about these two areas.  While we are in no way close to experts, we are parents of a child with LCA with the RDH12 gene effected, and we have spent the last two years soaking up and deciphering as much as we can about our daughters condition.  Just like any of you would have if it would have been you.

THIS POST IS GOING TO BE LONG!!  But worth it, I hope.  Read, take a break, and come back.  I hope you learn a lot that you didn't know about RDH12 before.  Knowledge is power.

So, since many people come here when they are searching this topic, I thought Mat and I would provide a few answers to questions that many of you seem to have.

"If a sister has LCA and a brother doesn't is it still hereditary"?

The short answer is yes.  With LCA, it is a recessive disease, which means both parents have to be carriers.  So in our case, both Mat and I are carriers of LCA on the RDH12 gene.  Finley had a 25% chance of getting RDH12 LCA, and so did Arlington.  Arlington did not get it, and Finley did.  If we had another child, the odds would be the same.  It has nothing to do with siblings having it/not having it - in this case, it is the parents.
Another questions was from one of our new families.  I think it is a good question, and while we don't have all the answers, I thought that Mat's answer was great.

What is the status at U Penn? How long will the trial take in the mice? Then how long before FDA approves it? After that, is there a safety trial? The after that, FDA approval? 
We funded Dr. Bennet to generate the virus that delivers a good copy of RDH12 to cells and then test that virus in a mouse that lacks a functional RDH12 (like our kids).  This work should be completed in a year’s time.  So by next March, if things go as planned, we will have an RDH12 gene therapy and proof that it can correct an biological issue caused by the loss of RDH12.  If that goes as planned – and I should say “if” because this is still an experiment and you can always get an unexpected result – the next step would be a safety study.  Right now, we are actively fund raising with the hope that when March rolls around next year we will have the money necessary to enable this safety study without delay.  Now, if the safety study works out – and here the “if” is not really an “if” because the RPE65 gene therapy work has really already established the safety of the delivery virus and there isn’t an expectation that the inclusion of RDH12 instead of RPE65 will change that – then we would be able to move onto registration with the FDA for a clinical trial.  Essentially, it is not totally unrealistic to think that we are 3-4 years away from a clinical trial for an RDH12 gene therapy.  And let me say that is a remarkably fast time line. 

In all, I would say that we are cautiously optimistic that things will play out like I described all the while remember that it could fail at any number of steps.
We also have people who are curious about what Vitamin A could do to vision of a person with RDH12 LCA.  As some of you know, from the researchers we have spoken too, and Mat's reading of many scientific papers, it looks like Vitamin A could be harmful to kids with RDH12.  Harmful to their vision, that is. 

For most people Vitamin A is good for the eyes.  What is the case for kids with RDH12 LCA?
 (this is another one answered by Mat.  As you all know, he is a Geneticist)
First, I don't want to give the impression that what I am saying is absolute fact.  This is just my interpretation of what I have been able to glean from the literature.  You are right, vitamin A is typically considered to be good for sight.  That is because it is a key part of the retinoid cycle or visual cycle.  The visual cycle is part of the process used by the eye to detect light (pasted in below).  But this process creates a toxic compound, 11-cis-retinal.  RDH12 is responsible for detoxifying 11-cis-retinal to 11-cis-retinol.  Without RDH12, you might be getting a build up 11-cis-retinal plus other reactive oxygen species that RDH12 reduces in the retina.  The build up of these types of species could be leading to the retinal degeneration.  Now, getting back to Vitamin A.  Because this pathway works like an assembly line, the more you put in one end, the more you get out the other end.  So, more vitamin A begets more 11-cis-Retinal which you might assume is bad for an individual with RDH12 mutations. 

Of course, I keep using words like could, might, and other qualifiers because this hasn’t been proven.  I have run this by people doing work in this area and they seem to think these are reasonable suppositions.  So, this is way we have decided not give Finley any Vitamin A supplements.  We don’t actively try to restrict Vitamin A from her diet because she still needs it.  We just don’t give her any extra.  Instead, we focus on supplementing her diet with antioxidants like Vitamin E with the idea that they might be able to make up for some of the missing RDH12 function.  That they can reduce these reactive oxygen species and help slow degeneration.

What is the incidence of RDH12?

RDH12 is one of the more rare forms of LCA.  IT accounts for only 4% of the cases of LCA. 
LCA is a fairly rare disease, 1 in 100,000.  So then, when you consider that only 3 out of 100 of those 1 in 100,000 have RDH12 mutations (3 in 10,000,000), you are talking pretty rare.  And out of the 16 known genes for LCA, it is typically in the bottom quarter of frequencies in many studies.
how do you cope with Finley on a daily basis... most importantly is she happy? how bad is her functional vision? is she able to tell you what she can or cannot see?

Finley is very happy and healthy.  She doesn’t really understand about her eyes – even at almost 5 years old.  She has never known any other way of seeing, so she doesn’t know what she is missing.  She knows that her eyes are “special” and she takes it in stride.  She rides a bike, takes horse back riding lessons, watches TV and movies, climbs, runs, plays.  She doesn’t have any restrictions, and we found that with most kids with LCA – they are very, very happy.  Even the kiddos with hardly any sight.  Us, as the parents, are most worried and wary of what is happening.  But the kids are great.

Finley has no central vision.  She has 20/100 in one eye and 20/200 in the other.  Children are very very hard to test vision acuity on, so the doctor’s don’t rely much on that until they are older.  We have had pictures taken of Finley’s retina each time she sees the retinal specialist (every 6 months) to see if the degeneration has gotten worse.  It really hasn’t – it has remained stable.  But that is how they know she is missing her central vision – her macula are black.  She has peripheral vision. 

She sits very close to the TV.  She reads print – just enlarged.  Everything we have done with her started in the last year (after she turned 4).  During the year when she was 3, we just kind of got introduced into the vision impaired world – at that age, they are really too young for formal training.  But she did get to test things out.  Now we work on Braille, but she still reads print.  She works with a cane just to get used to it.  She does not rely on it every day to get around at this point.

We make her life as normal as possible.  She is not our only child, so she just kind of fits right in with what we are going.  Our eldest is unaffected, and our middle child was adopted.  She keeps up with them in play and activities without many problems.
What will the $250,000 that you are raising this year be for?   Will all of it go to research for RDH12?

After determining that the potential gene therapy works, we next must determine that it is safe.  Therefore, if everything goes as planned in the first year of Dr. Bennett’s research, the potential treatment will then need to be assessed for its potential to cause any unintended consequences in order for its development to progress.  That is what the entirety of the $250,000 is going towards.  Our goal is to secure these funds within in the next year to ensure a seamless progression in the gene therapy development, so phase 1 can move to phase 2 without pause.  Making sure this next step happens as quickly as possible is because this is really the last hoop that has be jumped through before we can think about getting this therapy into humans, into our kids.  If we can show that the therapy is safe and effective, we have something that could really benefit our children.

Is RDH12 the most severe form of LCA?
Not even close.  Isn't that good news?  There are many different types of LCA, and even within those types, there are large spectrum's of differences.  But there are some where the children are completely blind.  Some where the children have other organs that are affected, like their kidneys and their heart.  There are some that also lead to deafness as well as blindness.  There are some that are degenerative and some that are not.  We feel very lucky that 1) she was born with sight and at almost 5 years old, still has pretty good vision for a kid with LCA and 2) that she has no other health problems because of her diagnosis.
How can you be so sure that your daughter and others will definitely benefit from this gene therapy or even be suitable candidates?  Of course i hope it does work for Finley but what if ...? 
(answered by Mat)
Really it translates like this, the more functional cells you have, the better the potential results.  And that really goes for any treatment, not just gene therapy.  If the cells are already dead, no treatment is going to bring those cells back to life.  The only way you are going to get back live retinal cells is with something like stem cell therapy and that is a good ways off. This is one of the reasons we are in such a hurry to push a relevant therapy for RDH12 to the finish line.  The longer we wait, the less functional cells that are left, the less sight that can be recovered. The number of functional retinal cells is not a qualification criteria for a clinical trial based on previous work.  In the successful RPE65 gene therapy trial, the participants ranged from a kid like Corey Haas that still had some usable vision (but still pretty bad - you can see a video of Corey before (and after) the gene therapy on the RDH12 site) to those that only could sense movement right in front of their face - essentially completely blind.  

We believe, based on this, that Finley will qualify and benefit from gene therapy, AS LONG AS SHE STILL HAS ALIVE CELLS TO WORK WITH.  In the case of RDH12 LCA, the cells are dying.  Those cannot be brought back.  Our hope is to preserve what she has.
Why gene therapy and not a medication?  Have you thought about investigating if a company like QLT will start a drug for RDH12 for instance?
(answered by Mat)
Here is the general thinking behind the steps we have decided to take. 

First off, gene therapy is actually as close as you are going to get to a one size fits all approach when it comes to therapeutics.  Essentially it is the ultimate in personalized medicine.  It gets at the root cause of the disease and it designed to treat the specific cause for the person being treated. 

But more to the point, gene therapy does not require knowledge of the mechanism of retinal degeneration.  As I say above it goes to the root cause, the driver of the disease.  In this case, the lack of retinol dehydrogenase (RDH).  You return that function to the cell and you should regain normal function.  The problem with seeking another avenue of treatment, like a small molecule, is that you need to know why the loss of the RDH12 is causing the retinal degeneration so you can intercede in that process.  In one of your other messages you mention QLT and their treatment.  That treatment is essentially a retinoid replacement therapy.  They chose to take that route because it is believed that interruption of the retinoid cycle is the driver of the vision loss in RPE65 and LRAT LCA.  So if you fix that, you fix the disease.  The problem is that that is not the issue with RDH12 LCA and QLT has actually said their treatment does not work on RDH12 LCA.  In fact, with the information that is out there, this therapy could actually make matters worse for kids with RDH12 by actually generating more free radicals that damage the retina (this is the same reason we don’t supplement Finley with Vitamin A – it is a retinoid).  Until the mechanism for RDH12 retinal degeneration is nailed down, drug development in for RDH12 LCA will be guess work.

That is not to say there aren’t intriguing leads.  The researcher in Oklahoma that works on RDH12 LCA  is trying different antioxidants and seeing some success.  Eyecyte Therapeutics has a drug in early animal testing that could be applicable.  But these are all could be’s and maybe’s based on the current knowledge.  The decision to put our limited resources behind gene therapy is because it is the most relevant approach, the ready for development, the one with the greatest depth of knowledge behind it, and the only one that is a real cure (small molecule options are more of a patch).
What made you decided to form your own Fund for RDH12?  Why not just give money to the bigger groups out there like Foundations Retinal Research and Foundations Fighting Blindness?

 I want to start off by saying that Foundations Retinal Research (FRR) and Foundations Fighting Blindness (FFB) are two wonderful organizations.  We wouldn't be where we are today with Finley without either group.  FFB was our first contact when we found out Finley's diagnosis.  They do annual vision walks to raise money for all different types of blindness.  They helped us get through the first year of Finley's diagnosis with wonderful contacts, great support, and amazing funding for retinal research all across the country.  But - and this is a big but where we are concerned - they cannot designate our funds that we raise to a specific cause.  We understand that - they are a big organization and they spread their money out evenly across the board with many different eye disorders.  But we needed to focus on a cure for our daughter.  And we knew in doing that, we would be focusing on a cure for other children who had RDH12 LCA.  As for FRR - they focus specifically on LCA.  Which is wonderful.  They are the organization that held the LCA conference last year we attended, and we learned so much by going to that conference.  And this is where we met 3 other RDH12 LCA families, as most of you know.  FRR fueled our fire to make us realize what our goal was, and confirmed in our minds what we needed to do for our family.  Again, FRR is an amazing organization that funds all types of LCA research.  But their focus right now is on LCA5 and LRAT - two other types of LCA.  Not RDH12.  So, we knew we were on our own.  And look what we have done with ALL of our family and friends?  Look where we are - less than a YEAR after Mat and sat in Philadelphia at the LCA conference and confirmed that we would be making our own foundation.  We did it.
What services is Finley receiving at this time?  Why did you start them if you are confident that her vision disorder will be cured?

I would like to quote another one of our RDH12 families here by saying " we are not holding on to hope that they will be cured, we are just living our lives each day and dealing with obstacles as they come along."  While we are fairly confident and the researchers and doctors are fairly confident that RDH12 LCA can be cured, we cannot be blind to the fact that it is still research and things don't always go as planned.  Mat has a great shirt that says "If I knew what I was doing, they wouldn't call it research".  This shirt always makes me laugh, but also shows a lot of truth.

Finley received services from a teacher of the vision impaired (TVI) at least 2 times a month.  This is typical for someone with Finley's vision acuity and age.  Next year in Kindergarten, she will receive braille every day for 45 minutes, and will  have a TVI helping her out 3-4 times a week.  Also for now, she is learning to use a cane.  We practice in public places as often as we can and her orientation and movement specialist sees her one to two times a month to see how she is doing.  Again, because she can get around without the cane (thank goodness) this has not been a big focus.  She is working on braille - she knows about 15 letters so far.  She recognizes them and can form them on her brailler.  We don't work on it as often as we would like, but review it 1-2 times a week with her and add letters as we can.

Whew!!!  Did you make it?  I hope the pictures of our goofy girl to help you get through it.  But now I hope you know a little more.  If you have any questions you would like answered, you can email them to
 or leave us a comment!!!  We love hearing from you.