Canavan’s Disease FAQ

 Answers to questions commonly asked about the disease and about Vincent Warden

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Section One: Canavan Overview

Section One: Canavan Overview

 What is Canavan’s disease?

It is an extremely rare degenerative genetic brain disorder that significantly impacts a child’s ability to   develop and ultimately leads to an early death.  Canavan’s disease belongs to a group of genetic brain disorders called leukodystrophies.

What is a Leukodystrophy?

“The leukodystrophies are genetically determined progressive disorders that affect the brain, spinal cord and peripheral nerves. The term leukodystrophy derives from the Greek words "leuko" meaning white and referring to the white matter of the nervous system and "dystrophy" meaning imperfect growth or development.” from www.ulf.org

Other leukodystrophies include ALD (Adrenoleukodystrophy), Alexander’s Disease, Krabbe’s disease and several others.  They are all severe and most result in childhood death.

Jim Kelly’s, former Buffalo Bills quarterback, son Hunter suffers from Krabbe’s Disease.  Earlier this year, Hunter reached his seventh birthday, which is extremely uncommon for kids with this especially brutal disease. 

What is happening in the brain to cause the problems associated with this disease?

The gene associated with the production of aspartoacylase does not work properly in Vincent’s brain, which leads to an accumulation of NAA (N-acetylaspartic acid).  This acid cannot be broken down and creates a ‘sponginess’ in his brain that leads to the degeneration of myelin (white matter).

What are the symptoms?

The destruction of myelin causes severe neurological problems.  Delays in developmental milestones are the first presentations that parents notice.  Also, rapid growth in head size in another sign.

Canavan children first have hypotonia, or low muscle tone.  They generally cannot hold up their own head and have trouble with gross motor skills.  The hypotonia often leads to hypertonia, where muscles are very tight and rigid.  Physical therapy is required to attempt to slow this progression.

These kids do not crawl or walk.  They may be able to coo and make baby noises, but they do not talk.  Some kids have hearing problems and most kids have optic atrophy, but they can see.

Most kids have trouble eating and sleeping.  Trouble eating often leads to the requirement of a feeding tube later in life.

Seizures can also be common with Canavan kids and must be monitored closely.

 What is the life expectancy for these kids?

Official statements we found on the web often limit life expectancy to 2 or 3 years.  However, we found many cases where children are still alive at 8, 9 years old, even some in their early teens.

 What are the treatments?

There is no cure for Canavan’s Disease, and treatments are just generally supportive

 There is some hope in experimental gene therapy (more on that in section 2

 How rare is this disease?  How many children have been diagnosed?

It is very rare with only 500 known cases ever documented in the US and it is estimated there are only 4000 worldwide.

 How do you get this disease?

First, it is not contagious.  It is a genetic disorder that is inherited from the parents.

Both parents must be carriers and then they have a 25% chance of having a child with the disease.  There is a 50% chance the child will be a carrier with no symptoms and a 25% chance the child will not be carrier at all.

The disease is most common within Ashkenazi Jewish population, but as is the case with Vincent, non-Jewish families have reported most recent cases.

 Do carriers of the disease ever experience symptoms or problems later in life?

 No, carriers of the disease are asymptomatic and have not reported problems.

Are there medications that help manage symptoms?

There are a couple of drugs that help manage head size and irritability.  Calcium Acetate and Topomax (Topiramate) have both shown some effectiveness in helping Canavan kids.

Multi-vitamins, CoQ10 and SOD (Super Oxide Dimutase) also have the potential to help slow down the disease.

How do doctors diagnose Canavan’s disease?  Are they sure Vincent has it?

An abnormal MRI is the first indication to doctors that a leukodystrophy is present.  Urine analysis is then used to confirm Canavan’s disease if a high level of NAA is present.

In addition to the MRI and urine analysis, genetic analysis is used to identify the specific mutation causing the Canavan’s disease.

Unfortunately, Vincent’s clinical presentation, MRI and urine analysis proves to at least 99% that he has Canavan’s.

How severe is Vincent’s specific case?

Although Vincent is confirmed to have the disease, he seems to be relatively functional as    compared to most Canavan children.  Our recent trip to Camden, allowed Vincent to be seen by doctors who have seen many Canavan patients and they all agreed he is one of the most functional Canavan kids they have ever seen.

As those of you who know him well, he is a very happy baby who eats very well (very, very well).  His quality of life is excellent especially when you consider where he could be with this disease. 

 Section Two: Gene Therapy

 What is gene therapy?

The general theory behind the therapy is that a chemical reagent is injected into the patient’s brain to transfer operative genes to replace the abnormal DNA.The functioning gene is synthetic, made in a laboratory in North Carolina. 

The gene is injected into the brain by using an adreno-associated virus.  This was described to us as a ‘Trojan Horse’ or a vehicle for the DNA to be introduced into the cells in the brain.

 What is the theory behind the therapy specific for Canavan’s?

The theory is that the functional DNA injected into the brain will then be accepted into the brain cells and eventually begin to produce the ASPA protein that is currently not being created.  If the protein is made successfully, the levels of NAA in the brain should decrease and Vincent should begin to have an increase in development.

Can you expect the injected DNA to be permanent?

This was a serious point of concern for us.  If the therapy would only create a temporary increase in ASPA protein that would eventually be destroyed, we were very apprehensive about going through with the therapy.  We have been assured that the functional genes are permanent.  It is possible that they functional genes may not actually produce ASPA, but permanence would not be the problem.

 Has the Canavan gene therapy been done before?

The first trials were in 1996 and in 1998 and used a different vector to deliver the genes.  Two patients went through the first therapy in New Zealand (1996) and then 12 more in New Haven, CT (1998).

The second set of trials using the same vector that Vincent will receive was first done in 2001 in New Haven and included 3 children.  The last trial was in 2003 in Camden and it included 7 children. 

What were the results?

The most important result is that of the 26 total children, there were no significant adverse events. 

The newer vector has proven to be the more effective, although all but one child have had varying degrees of improvement after their surgeries.  The youngest children do the best with the youngest in the trial with the new vector was 24 months.

 How is the newest trial different from previous trials?

With the latest vector proving to be relatively safe, the FDA has authorized the doctors to increase the dosage to make the transfer stronger and hopefully more effective.

Who will be performing the therapy and where?

Dr. Paola Leone Ph.D. is the director of the study and is based at Cooper Hospital in Camden, NJ.  She is the scientist behind the research for Canavan’s patients and is the only person doing such work.  The actual procedure will be done by a Neurosurgeon in Camden and follow up work will be done by a Neurologist and Pediatrician.  Contact information for all doctors involved is available if requested.

What exactly has to be done?

The procedure itself is fairly invasive.  Six holes, approximately a ¼” in diameter, must be drilled into Vincent’s skull under general anesthesia.  A fine tube is inserted and the vector is delivered directly into the ventricles of the brain at a steady, slow rate.  The holes are covered back up by the scalp and the skull re-grows to fill them in eventually.

What are the risks associated with this procedure?

There are always risks associated with any surgery and these risks are higher for kids with Canavan’s.  He is more susceptible to complications to anesthesia and he may heel a little slower than normal kids.  

The most serious risks associated with this specific procedure are adverse immune reactions, brain hemorrhage and infection.  All of which would be very serious and would require treatment.  There is always the outside chance of death due to any of these factors.  

The most tangible risk as we see it, is the risk that the procedure will not improve Vincent’s quality of life and that he may actually lose skills that would have taken years for him to lose had we not gone forward with the therapy.

How long is the recovery?

Vincent will remain in the hospital for 3 to 6 days after the surgery.  It will take some time with a fair amount of pain and discomfort before he will be back to normal, perhaps a couple weeks, but we cannot say for sure.

What is the timeline and/or schedule?

The first step in the process is to get baseline testing done to determine if Vincent is a good fit for the study.  This process includes MRI/MRI Spectroscopy, Neurological exam and Pediatric evaluations.  The first baseline testing was completed the week of Sept. 24^th of 2004.  

The next step will be to repeat the baseline tests right before the actual gene transfer surgery.  This whole process will likely take at least 2 weeks and will happen no sooner than Feb 05 and no later than Jun 05.  

Numerous follow up trips to Camden will be required over the next two years as doctors follow up on the success of the treatment.  We will get to know the route to Camden/Philly very well over the next couple of years.

Why do you want to do this for Vincent?

This is easily the most difficult decision our family has ever had to make.  The risks are significant and the overall stress, pain and discomfort for all of us will be challenging at best.  

We decided to make our decision based upon what has the greatest potential to serve the quality, if not the length, of Vincent’s life.  We all know that the therapy is not a cure and that Vincent may not be with us as long as he was supposed to be, but the time he has will be as good as it possibly can be.  

We will not regret having made the decision that we have made to go forward with the therapy, but we may very well have regretted not doing it.  We have to do this for him.

What are the doctor’s expectations for results?  

The doctors are very careful about what they expect from the procedure.  The consent forms and official communications promise nothing.  

With that said, I think the doctors are very optimistic in what can be achieved in Vincent’s case because he is already such a relatively functional child and because he is so young.  

Most expectations are based upon the results other children have gained in previous trials.  The other kids have had life expectancy improved and have found benefits in increased muscle tone, improved eating abilities, fewer seizures, better communication and mobility.

What are your expectations for results?

Our expectations are not specific.  We are not allowing ourselves to get our hopes up too much.  We hope that Vincent may begin to do some of the things normal children do because we think he has enough cognitive ability to know what he wants to do, he just can’t and it frustrates him.

How long until after the recovery before you may see results?

I don’t think anyone knows for sure, but once he heels from the actual procedure, the functional DNA should begin to create ASPA immediately.  If results are to begin, they should start soon after he recovers and gain over time.

Can the damage that has already been done be fixed?

Maybe.  This part is still pretty unknown.  He will never be anything close to normal.  It seems possible that the myelin he has already lost may not matter that much if he begins to create new myelin with the gene therapy.  So, essentially, he may overcome the damage, but the damage cannot be repaired.

  Will he require additional treatments?

It seems like depending on the success of this treatment, he could benefit from more gene transfer procedures in the future.  However, no funds are available after this next trial, so it would depend on the availability of another NIH grant.

  Has Vincent been accepted as one of the patients for this next trial?

We believe he has been accepted as he has proven to be a very good case for the study.  He would only be disqualified from the study if he seriously deteriorates over the next couple of months and we are doing everything possible to keep that from happening.

Are there any alternative treatments?

Not really.  Bone marrow transplant is the only other treatment that has any chance of helping, but this procedure is extremely difficult and really only works if performed at a very young age.

What are the costs?

The costs are very significant, at least $300,000.00 for all of the testing and the procedure itself.

What costs will you be responsible for?

An NIH grant that expires next year will cover the procedure itself and much of the follow up    testing.

The production of the viral vector is not covered by the NIH grant and requires funding be raised through parents and other Canavan foundations.

Section Three: Fundraising

What fundraisers are planned for the near future?

A benefit is planned for November 21, 2004 at the White Buffalo in Loveland, CO.  There will be a pool tournament and a silent auction as well as door prizes.  Also, a portion of all food purchases will be donated.

A fly fishing auction will be organized later this year where hand tied flies and other equipment will   be donated.  Much more info on this event will be coming in the near future.  

Future dinners and events are in the works, but details are not yet decided.

Are there other possible donors?

Attempts to raise money from the public are underway outside of the fundraisers that are planned.  Our hope is that a major media outlet may provide publicity for our cause and general donations could be raised from people we do not know.

I have also put in an official request for a donation from my employer, Nelnet.  They are a very active giver supporting all kinds of children’s charities and hopefully they will provide a donation to the cause.

What will the money be used for if the funds are donated to Cooper Hospital in Vincent’s account?

A portion of all funds donated to for Vincent’s therapy will be sent directly to the Cooper Hospital to help pay for the viral vector that will act as the transport for the gene therapy.  These funds will also be used to further the research effort in both human and animal cases to try and find the next possible therapy and maybe even a cure. 

What will the money be used for if the funds are donated to Vincent’s Hope account?

Certain fundraisers (the event on the 21^st for example) will be to raise funds for Vincent’s Hope.  These funds will be used by the Warden family to augment expenses associated with travel to and from Camden, therapeutic devices (bath equipment, car seats, mobility devices, therapy devices) and with medical expenses not paid by insurance.

An account has been established in Vincent’s name and all funds are carefully used only for expenses directly associated with Vincent’s care.

What are the expected costs associated with caring for a child with Canavan’s disease?

Our insurance is really pretty good.  Most of the doctor care is paid for to at least 80%.  This leaves a significant amount for the family to pay out of our own pocket.  The actual cost so far has been over $3,000 and will likely rise to at least $5,000+ in the next couple of months.

Travel is also going to be very expensive with at least 10 trips to Camden being required over the next 12-18 months.  This will be at least 5 to 8 thousand dollars more.  

Finally, medical equipment is very expensive (I had no idea).  Our insurance will cover a pediatric wheelchair for Vincent, but bath equipment, car seats, standers, therapy devices…etc are not covered and we could easily spend another $10,000 in these expenses alone.

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