Category: Treatment

For this particular post,  let’s start with all the necessary legal disclosures.

The statements contained herein have not been evaluated by the Food and Drug Administration. The information contained in this blog is intended for educational purposes only.  This information is not intended to be used to diagnose, prescribe or replace proper medical care. The information described herein is not intended to treat, cure, diagnose, mitigate or prevent any disease.  Always consult a physician before initiating any supplements or regimens.

On this journey, there came a point where we had to determine our philosophy of care.    When your doctor tells you there is practically nothing s/he can do for your child, it might alter your perspective on medicine.  Some people have relatively strong opinions before encountering a condition such as GM1.  If so, perhaps those opinions guide their philosophy of care immediately.

Our philosophy of care continues to evolve and we will allow ourselves the space to change our philosophy depending on the challenges we encounter and the decisions that will need to be confronted.

Last year, we briefly corresponded with a father from a foreign country who told us he developed a homeopathic regimen and medicine that ceased the progression of GM1 in his child.  Initially, he offered to send us the medicine he created free of charge.  He told us that people in countries other than his own are unaware of the treatment he developed.  He described a regimen of oral enzyme supplementation of beta-galactosidase, a lactose-free diet, and oral aloe supplements.  The enzyme supplement was prepared by a homeopathic pharmacy in his country using beta-galactosidase obtained from Novo Nordisk.  Beta-galactosidase is the particular enzyme that is deficient in those suffering from GM1 Gangliosidosis.

Our doctors told us very clearly that they never heard of this regimen and it would be unsafe to administer any medicine, homeopathic or not without truly knowing the contents of it.  Simply put, while unlikely, something bad could occur.  Finally, there are no official or peer-reviewed papers/studies outlining the scientific validity of such a regimen.

Ultimately, we dismissed the idea of using the enzyme from this father.  The intriguing part was the thinking behind the elements of the regimen and also the true sincerity of this man’s belief in his treatment.

There is an amazing true story about another father named Augusto Odone who developed a treatment for a disease called adrenoleukodystrophy (ALD)  for his son Lorenzo.  There is a widely released film that portrays this particular story.  It’s called “Lorenzo’s Oil.”  This film was released in 1992, starring Nick Nolte and Susan Sarandon.  The father we encountered likened himself to Odone.  Adrenoleukodystrophy is not considered a solved problem today and it is a truly devastating condition just like GM1.  If “Lorenzo’s Oil” is administered early enough, it is thought by some to be helpful to asymptomatic ALD patients.  Augusto Odone received an honorary doctorate for the creation of Lorenzo’s Oil from the University of Stirling.  His son lived to 30 years of age, well beyond the life expectancy estimated by his doctors.

Doctors told us that there are many unfortunate stories about desperate parents being duped by people who claim to have a cure for GM1.  The father we encountered wanted very little in return for his medication and he seemed sincere.  Upon examining images of the father’s child and news coverage from his country, it appeared that his child was still afflicted by GM1.

The father’s explanation was that the proposed regimen was not a cure, but mitigated the progression.  He said his child received the treatment too late and that the treatment could not reverse the disease completely.  He said his child’s vision improved.  His child wore glasses and then no longer required them.  The father went as far as to say that his treatment helps infantile/Type 1 cases which are the most severe.  I asked if there were other GM1 families who could confirm these results.  He offered us one email address of a grandfather of a GM1 child in the US.  We managed to contact the grandfather who said his grandchild did not experience any benefit from the regimen.

We asked some doctors about the oral enzyme supplementation.  They were very doubtful it would be of any assistance.  The reason is that although beta-galactosidase is readily available, it is composed of molecules too large to cross the blood brain barrier.  GM1 is most problematic because of the effects on the brain and central nervous system.  Furthermore, the doctors said the enzyme would not be distributed in the body beyond the large intestine.  Nonetheless, the intriguing part of oral enzyme supplementation is something called the gut-brain link, the notion that the gut can influence the central nervous system.  There are also probiotics available that are sold based on the premise that they increase beta-galctosidase production in the gut.  We consulted a naturopathic doctor who thought enzyme supplementation from a known source in the US would be worth trying.

The father’s idea that his child should follow a lactose-free diet is because beta-galactosidase is the enzyme responsible for metabolizing galactose.  A major dietary source of galactose is lactose.  The idea is that reducing the intake of lactose might cause the body to require less beta-galactosidase.  Lactose-free milk sold to people with lactose-intolerance is created by adding beta-galactosidase to milk.  This particular idea seems logical from a layperson perspective.  If your body has a deficient supply of an enzyme used to metabolize galactose, it might not be a bad idea to avoid foods containing galactose.

The problem with this idea is that beta-galactosidase is also required to metabolize galactans.  Galactans are a type of complex carbohydrate contained in legumes, such as baked beans, kidney beans, chick peas, soy products and so on. Galactans are also present in green and yellow (wax) beans, cabbage and brussels sprouts and plant tissues.   Furthermore, galactose can be produced within the body through hydrolysis.

It’s very hard to eliminate all sources of galactose from the diet.  One doctor said galactose is required by the body, required for life.  Still, there is an interesting coincidence that we observed.  The clinical trial we are participating in combines the ketogenic diet and the medicine miglustat.  Due to the ketogenic diet, Iris consumes no lactose and hardly any vegetables, especially the ones with galactans.  This means that her consumption of lactose and galactans is extremely negligible.

Another interesting tidbit is that people who have a lactose intolerance take lactase.  A particular form of lactase is beta-galactosidase.  The enzyme that is deficient in GM1 is available in pharmacy’s everywhere at very minimal cost.  People take lactase supplements freely and without fear because it is effective in addressing lactose intolerance.  Finally,  this is likely unrelated, but curiously, Iris was lactose-intolerant as a baby.

Now onto discussing oral aloe supplementation.  Aloe drinks are widely available.  Aloe is an ancient treatment dating back to the dawn of civilization.  Still, there are definitely some warnings about ingesting aloe.  Most people think of it for topical usage, e.g., cuts, burns, itches, and bug bites.  Oral aloe is also a homeopathic remedy for constipation.

Interestingly, there is a publication from May 2013 in the Journal of Alzheimer’s Disease  that claimed that a mixture called Aloe Polymannose MultiNutrient Complex (APMC) reversed the effects of Alzheimer’s disease, a neurodegenerative condition just like GM1.  Aloe or mannose is thought to cross the blood brain barrier by some.  If you search around the internet, there are some people who claim diet, enzymes, and/or aloe cured them of horrible conditions such as cancer and autism.  Of course, these miraculous stories lack hard evidence and one has to wonder if such cases have been verified.  However, there is true science that ties mannose  to cellular trafficking and recycling in what is called the mannose-6-phosphate pathway.

The depth of our desperation to save our sweet girl is now completely evident.  Who in their right mind would go so far as to research all these claims?  We’re not scientists or doctors, but given such a rare disease, there are not a whole lot of people out there with whom to discuss all this.

Our palliative care team told us that people want to try things out because it  can be very difficult psychologically to do nothing.  One should be careful with all these decisions and consult doctors.  Finally, the reality is that even if a “cure” were to arrive tomorrow as an official clinical trial, it would most likely involve brain surgery and would be fraught with many unknowns and risk.  So many of these questions and issues are very interesting academically. However, when the life of a loved one is involved, it’s not academic.  It’s all very real.

If you have never been faced with a very serious health condition, you might not think very much about health insurance.  In the United States, if you are fortunate, you have coverage through your job or you bought a policy on one of the new government web sites.  Hopefully, the benefits are reasonable.  You pay your copays, perhaps $25 or so  when you see the doctor for a physical.  Perhaps, you have a few prescriptions here or there, but nothing too major.  This was the way we were, extremely fortunate, somewhat naive and not overly concerned.  We had physicals once a year.  We did not really think all too deeply about the exact details of our health insurance policy.  Ignorance is bliss.

We believe our health benefits are good, even above average.  We continue to learn about our policy and the specifics of how we define good coverage.  Now with the Affordable Care Act,  the general population has probably learned a bit more about health insurance, shopping on the exchanges, and reading about the various policies and options.  Even in good health, I’m sure there are some people who pay careful attention to their insurance policies.  Kudos to those individuals!  It’s incredibly important.  GM1 is an extremely strong forcing function that emphasizes the importance of health insurance.

The most harrowing experience with our insurance so far was trying to get the coverage for miglustat for Iris.  Miglustat is not FDA-approved for GM1.  Our doctors told us that miglustat is possibly our one and only chance to slow down the progression of the disease.  It’s absolutely terrifying when obtaining a medication for your child is in the hands of an insurance company.  When we first started out on this journey, I was extremely poorly outfitted for battle.  I was armed with my flimsy insurance card and a 1-800 phone number.

The first group of doctors we saw after diagnosis recommended miglustat at the first appointment where we met them.  I had already read about it a bit.  Naively, I thought they would write a prescription and we would go home with the drug in hand.  This is absolutely not how things unfolded.  This is not Tylenol or an antibiotic.  This is a drug that costs more money than nearly anyone in the entire general population can afford.  No one can afford miglustat without insurance, except the fabulously wealthy.  To be specific, for the particular dosage recommended by our doctors, the cost is more than $1000 a day.  Perhaps your insurance gets a better rate than ours or perhaps you live in another country where the drug is cheaper.  Still, who can or would want to shell out the cost of this drug without insurance?

At the first appointment where the drug was mentioned, we were told that the next step was the confirmation of the diagnosis through DNA testing.  We were told that the DNA testing would take 16 weeks.  Before the DNA testing, we had 2 enzyme panels to confirm the diagnosis.  This particular team of doctors seemed to want to wait to prescribe the medication until those DNA tests were conducted.  In retrospect, perhaps they also wanted to give us the space the think about the prescription.  At that same appointment, the geneticist mentioned the names of three specialists whom he considered the best in the country with respect to GM1.

Hours after the appointment, I sat at my laptop, wracking my brain, trying to recall the names of the three specialists that were mentioned.  I emailed the other doctor who was present at the appointment to ask him for the names of the specialists.  He was the only doctor who gave me his email address.  Frankly, I know he later regretted giving me his email.  I barraged the poor doctor with questions.  Learning was my way of coping.

Unfortunately, he did not remember the names of the specialists either.  I started searching the internet for various doctors who specialize in lysosomal storage diseases, carefully perusing the names of the doctors.  Eventually, after hours of searching, I recalled all three names, using Google to prompt my memory.  I regretted not writing down the names at the appointment.  I like to believe that I am a relatively organized person.  The high level of emotional distress at these first appointments made it incredibly hard to process or remember anything.

16 weeks of waiting for a DNA panel before initiating treatment was simply too much for me to bear.  I contacted the specialist who was closest geographically.  We made an appointment to see the specialist in the Midwest, more than 1500 miles away and they promised to help us initiate treatment.  The first available appointment was approximately 8 weeks following the diagnosis.

It was the doctors in the Midwest who first initiated the request to get insurance coverage for miglustat.  In retrospect, I’m so grateful that we kicked off that process of getting insurance coverage before the DNA testing was complete.  The DNA testing took forever.  The insurance approval process to get miglustat took forever too.  The processes we endured were slower than any hospital dramatization on television would ever have you believe.

The first attempt at getting a prescription was immediately rejected.  Prior authorization was definitely in order.  For a drug as expensive as miglustat, of course, prior authorization is required.  We learned that we basically had 3 shots at getting an approval.  Think of it as three strikes and you are sh*t out of luck.  Reading the word “denied” was like twisting a knife in my gut.  The second appeal was also denied citing the lack of FDA-approval for the drug for GM1.  Denied.  Denied.  Twist.  Twist.  The doctors told us that for other patients and other companies, “sometimes is just goes straight through.”  Other families, other companies…

Our local neurologist tried to stay positive, telling us “insurance companies usually come around.”  What if we were in the group for whom the company does not “come around”?  Iris is already in that incredibly tiny minority of those diagnosed with GM1.  How could we have confidence that fate would not have its way with us again?

By the time the second denial rolled around, complete panic had set in.  I started to harbor a high level of animosity towards our insurance company.  Isn’t the purpose of health insurance to pay for extremely expensive drugs and procedures?  I frantically formulated a plan on how to get the drug approved.

Our first neurologist mentioned compassionate use, i.e., asking the drug company to just give the drug to us.  This involved consulting another family in England who had obtained the drug directly from the pharmaceutical company and consulting their physician.  I was told that the CEO of the company is a good man, but otherwise, I was not sure how to proceed.  I contacted the company directly via an online form and spoke to someone on the phone who told me to ask our doctors about working with their specific compassionate use program.

I consulted one of the doctors in the Midwest about compassionate use.  The doctors in the Midwest had a ton of experience with getting the approvals.  Still, by the time I mentioned compassionate use and the second denial had occurred, those very same doctors told us that prayers were in order.  The prospects of getting the drug were waning.  Visions of selling every belonging we own to get the drug kept me up at night.

I contacted a patient advocacy organization and enlisted their help.  I started nagging all of our local doctors for letters of support to supply to the insurance company.  I sent a cute picture of Iris to be included in the appeal.  I wanted the insurance company to see the face of a little girl who needed this medicine as opposed to just seeing the black and white type of her medical records.

Through the patient advocate, supporting materials and letters were submitted from the National Institute of Health.  For the third and final appeal, an external review, in summary, we submitted 3 letters of support from our local doctors, a letter of support from the patient advocacy group, and we submitted the materials from the NIH.  The doctors from the Midwest included more than one hundred pages of materials that included medical records and relevant research.  All the documents were sent via certified mail.  The team in charge of the appeals said that in the past, appeals had been lost or the insurance companies claimed to have never received them.

The excruciating wait continued.

Ultimately, our primary insurance approved coverage.  We prevailed.  The third appeal was successful.  The external review panel approved the coverage in December 2013, 4 months after diagnosis.  Our primary insurance company conveniently neglected to tell us that they approved the coverage.  It was not until I called them for the n-th time in January that someone actually told me the coverage had been approved in early December.  I had to request a letter to document the official approval.  That letter did not arrive until the end of January.

I never realized the extent to which the parents are responsible for advocating for their children.   Of course, I have some inkling.  I am a responsible person and parent.   Still, somehow the extent of my role in navigating the healthcare system surprised me.  I was somewhat shocked when one of our main doctors told me that I am the one in the driver’s seat.   I never imagined the herculean effort that is required to manage this process.   The sheer number of emails and phone calls exhausted me.  We are so grateful that all the blood, sweat and tears yielded an approval.

Do not take your health insurance for granted.  Do not take your health for granted.  If your insurance company denies coverage, ask again and ask again.  Ask as many ways as you know how.  Do not stop until you get what you need for your child.

Dear GM1 Parents,

I want to share something with you that your doctors might not tell you.  Miglustat tastes like vomit.  Really.  For many children, even ones who do not have dysarthria or difficulty controlling their tongues, it’s impossible to swallow a pill.  Iris is not able to swallow pills and for now, the only way to deliver the medication is by mouth.

We originally tried to teach Iris to swallow pills.  We went out and bought sugar-free tic tacs and we bought several special cups that are supposed to help people swallow pills.  The tic tacs just rolled off her tongue and out of her mouth.

Standard parental advice would be to mix the medication into apple sauce or peanut butter or a food item so you can use to mask the flavor.  Standard parental advice does not apply to a truly strict ketogenic regimen.  Applesauce, nope.  Peanut butter, nope.  Bacon, definitely.  Actually, Iris does not like bacon…The taste is bad enough that you need a lot of the food item to mask its horrible flavor.

We were faced with a very difficult question: How do you get your child to take a medication two or three times a day orally when it tastes just awful?  In our case, the simple answer is that you don’t.  We absolutely had to come up with a magic way to get Iris to drink the medication.  So, here’s our formula:

• Sugar-free lemonade.
• 1 teaspoon of Cal-Mag/CALM
• A few squirts of liquid stevia

The sugar-free lemonade is the base canvas to mask the taste.  Try the ones with stevia first.  Our doctors told us to avoid aspartame if we could, but honestly, the aspartame ones taste better.  Given the choice between not being able to administer the medication at all or using aspartame, we had to switch back after trying stevia lemonade.

The Cal-Mag is a calcium magnesium supplement.  We use it to help with calcium supplementation due to the ketogenic diet for two reasons.  Iris can not have milk and other sources of calcium as much as one might normally.  Iris does love zero carb cheese though!  Also, the magnesium helps with digestion/regularity.  Lastly, the CALM has a raspberry stevia flavoring.

The liquid stevia is used to put the sweet taste over the top.

All kids are different!  I can not promise this will work for you, but it is how we manage.  A colorful and fun straw also helps. Oh, and a cute cup.  Good luck!

Iris is currently participating in a clinical trial.  The clinical trial is a regimen of a medication called miglustat (Zavesca) in combination with the ketogenic diet.  All the other clinical trials are either observational only or involve bone marrow transplant.  The one team we spoke to with respect to a bone marrow transplant required asymptomatic patients.   Unfortunately, Iris is not in that category of patients.  For our family, we are also not sure we would have chosen that path.

Miglustat is FDA-approved for Gaucher disease, another lysosomal storage disease that affects the brain.  The basis of the trial is threefold.  Miglustat is believed to possibly be more effective in combination with the ketogenic diet, perhaps as much as 300% more effective.  This belief is based off a single research study in rats.  The ketogenic diet is also used to control seizures.  Many GM1 patients suffer from seizures.  As of now, Iris is very fortunate to not have seizures.  The diet is also used to mitigate the gastrointestinal side effects of miglustat.

To be clear, some clinical trials are successful and some are not.  There is a reason it is called a trial.  Furthermore, this specific protocol is not universally accepted.  We are very happy to participate in the trial.  There’s really nothing else to try.  We are hopeful that the regimen is helping Iris.  However, it’s not a cure.  Hopefully, it’s a way to buy time until a true cure or another treatment emerges.

In our own experiences with the regimen, Iris did cease toe-walking after initiating treatment.  However, we had also increased physical therapy at the same time.  We thought that her walk possibly improved.  Then, other symptoms emerged.  Her gait changed in different ways and not for the better.  We also thought that her speech might have improved for a bit, but that also can come and go.

There are 2 aspects of the trial that have clear evidence.  Limiting carbohydrates does relieve the gastrointestinal side effects.  The ketogenic diet is proven to help some people with seizures.  It’s been used for quite some time for that purpose separately from this particular study.  In general, there are so few patients to verify results.  It can also be difficult for the patients to participate in studies in distant locations.  Some other GM1 families told us the regimen helped their children, but the evidence is primarily anecdotal at this point.

Technically, Iris is in ketosis, so the diet she follows is ketogenic.  However, we achieve ketosis through the Modified Atkins diet.  This is a different approach from the more complicated true ketogenic diet involving ratios of fat and protein and calorie counts.  So far, we have been fortunate because Iris seems to be able to tolerate Modified Atkins.

She is allowed 15g of carbohydrates a day.  To put that in perspective, 1 teaspoon of sugar has 4.2g of total carbohydrate.  All the carbs Iris consumes are from fruit and vegetables only.  Yes, vegetables have carbs.  Low carbohydrate is not the same as gluten-free.  This means there is basically never dessert at our house.  There is no bread basket.  There are no ice cream sundaes, no Halloween candy, and no chocolate bunnies.  There is not even true birthday cake.  There are ketogenic cream puffs.  If we make any sweet at all, it is prepared using a sweetener such as Stevia.  The ketogenic diet can cause weight loss and that’s the last thing GM1 kids need.  To avoid weight loss, the diet incorporates lots of fat to balance the absence of sugars or carbohydrates.

Iris’ brother Carter has known the word “carbohydrate” since he was 3.    Iris has followed this regimen for nearly a year by mouth.  Some other children have feeding tubes and use a keto liquid formula or a blenderized diet.   We travel with our own food and snacks always.

It is very difficult to establish indisputable evidence that the treatment is effective.  Once a course of treatment is established,  one can not know the road not taken.  One world specialist in GM1 went as far to say that if it were possible to extract the brains of the patients and analyze the brain in a  petri dish, it would still be hard to measure the success of the treatment.  Another doctor told us that short of a complete miracle and reversal of all symptoms, there can be many gray areas.  I don’t know of anyone who experienced a complete miracle, i.e., a cure for GM1, but we sure would love one!