NIH | HOPE FOR KATHERINE BELLE

It’s the dawn of a new year and new possibilities. So much has happened since our last update, so let’s start there.

Katherine entered the EPI-743 clinical trial at the beginning of August. As a part of the trial, Katherine is monitored very closely – monthly blood work at home and/or at the National Institutes of Health (NIH) – to look for changes in her body while she’s on EPI-743/placebo.

What is EPI-743?
EPI-743 is a small molecule drug that is currently in clinical trials in the United States and Europe. EPI-743 was recently granted orphan drug designation by the FDA to treat patients who are seriously ill and have inherited mitochondrial respiratory chain disorders. EPI-743 works by improving the regulation of cellular energy metabolism by targeting an enzyme NADPH quinone oxidoreductase 1 (NQO1).

How is it given?
EPI-743 is administered orally or through a gastrostomy tube.

How was EPI-743 discovered?
EPI-743 was discovered and developed by Edison Pharmaceuticals by using a technique called high throughput screening. Edison evaluated thousands of chemicals that target cellular electron handling, and finally selected EPI-743 based on its ability to work, be orally absorbed, and its safety.

Why can’t my doctor just prescribe EPI-743?
EPI-743 is an experimental drug. It cannot be prescribed yet because the FDA does not approve it. Access can only be obtained through clinical trial enrollment. Results will be closely monitored at specified enrollment sites, under the direction of clinical research investigators.

Are there additional clinical sites being established? Additional trial sites are being established in Europe, Japan, and in North America.

In a nutshell, EPI-743 is the closest thing to hope available (through clinical trial) in treatment form. Mitochondrial dysfunction is linked to many neurological diseases such as Parkinson’s, Alzheimer’s, ALS, and other diseases like diabetes and some cancers, so this research is important for so many.

In March 2016, Katherine will begin the “washout” phase of the trial – a two month period when she will not take anything, placebo or EPI. (It takes around two months to completely leave your system, thus the “washout” before entering phase II.)

Each person we’ve encountered at the National Institutes of Health is above and beyond wonderful. We feel so fortunate to be a part of their program and could not ask for a better experience. We are grateful for the opportunity to meet so many dedicated and caring individuals.

Many people ask us if we think Katherine is currently on the placebo or EPI? We have no idea, honestly. For example, she hasn’t DRASTICALLY improved, i.e. started walking independently; however, she has maintained her skills and improved in some areas, so it is hard to say.

She started Pre-K in August and loves it.

She is getting more therapy than EVER with three physical therapy sessions, two occupational therapy, and speech therapy per week. One physical therapy session is done on a machine called Geo, which uses treadmill therapy to make her walk. Not only is it creating muscle memory and tone, it is creating new pathways to her brain. Very amazing technology.

All of these changes have happened since she started the EPI trial, so it would be hard to say if she’s improving because of school and therapy or because she’s on the actual EPI drug and benefitting from it. Time will tell.

Of course we fantasize that she’s currently on the placebo and something miraculous will happen in the coming months. Realistically, though, miracles have already happened – at the moment she’s thriving, happy, loving school, and hard working at her therapies. Katherine is the most determined person I know, truly.

This time last year she was still undiagnosed (and we believed she had INAD), we were thinking about her Wish trip, and I had just prepared what I feared would be her last Christmas meal.

Placebo or EPI, we are fortunate in so many ways.

The constant for us is that we simply do not know what the future holds. That will never change. All I can do is keep you posted as it unfolds. Your perspective changes so much on this journey. In the end, EPI may or may not be the answer. Sometimes the benefit isn’t improvement, rather it prevents further regression. The good news is that if it proves beneficial, then she can continue to have access to the drug even if it is not on the market. I am hopeful because clinical trials exist and science is making great strides daily. None of this would have been possible just a few years ago, so I am thankful that our daughter can possibly benefit and contribute to research, treatment, and hopefully a cure.

We wish all of you a very Happy 2016!

If you follow us on Facebook (YOU REALLY SHOULD!), then you’ve seen our recent updates and photographs from the National Institutes of Health where Katherine started the clinical trial for EPI-743. I know how confusing this information may seem if you are not living it, so I’m sharing basic Q & A below from the United Mitochondrial Disease Foundation. (It took us a while to figure out that the “EPI” part of this trial drug name is the acronym for the manufacturer, Edison Pharmaceuticals Inc.)

How is it given?
EPI-743 is administered orally or through a gastrostomy tube.

Are there additional clinical sites being established?
Additional trial sites are being established in Europe, Japan, and in North America. (http://www.umdf.org/atf/cf/%7B858ACD34-ECC3-472A-8794-39B92E103561%7D/EPI.PDF)

I first heard about this trial in September 2013 – just two days after we received Katherine’s first misdiagnosis for Infantile Neuroaxonal Dystrophy (INAD) – when Dave told me he found a trial that might be our only hope. He called the NIH directly and asked how we could get in the study. At the time we didn’t even know much about INAD or if it was even categorized as a “mitochondrial” disease, but Dave left no stone unturned. Fast forward to 2015 and a few months after Whole-Exome Sequencing (WES) results confirmed Katherine’s true diagnosis – NUBPL, Mitochondrial Complex 1 Deficiency. Dave’s early contact with the study (we were told EPI-743 wasn’t even in the building when he called that day) put us next in line when an opening became available in August 2015.

Once again we are reminded of the crucial role we play in advocating for our daughter. Nobody was going to make that call for us and ask how we could get our child on the list for the trial. YOU HAVE TO PICK UP THE PHONE AND DO IT YOURSELF. Thankfully, in our case, Dave did just that.

As always, Katherine was a trooper. Before starting the drug (placebo or EPI-743 – it’s a double-blind study so she will get six months of EPI-743 and six months of a placebo with a two month washout in between), a variety of tests had to be performed to establish a baseline.

Between needle pokes, a neuropsychological evaluation, and an EKG and Echocardiogram, Katherine enjoyed playing at The Children’s Inn at NIH. She loved the many playgrounds, art camp, therapy dog, family dinners, and being around other children.

We have a fridge full of EPI-743 or placebo vials and hope it will reverse or stop the progression of her disease. Only time will tell. In the meantime, we are moving forward.

Katherine starts pre-K this Thursday where she will receive speech therapy, occupational therapy, physical therapy, and water (aqua) therapy. Like everything, school will be a transitional time, so we are focused on making her life as “normal” and routine as possible. We go back to the NIH in early September, with follow-up lab work done here at home in between visits.

Awareness for NUBPL