Gene therapy gives patient a cure and a new lease on life

Brenden Whittaker (left), of Ohio, is a patient born with a rare genetic immune disease who was treated at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in a CIRM funded gene therapy trial. Dr. David Williams (on right) is Brenden’s treating physician.
Photo courtesy of Rose Lincoln – Harvard Staff Photographer

Pursuing an education can be quite the challenge in itself without the added pressure of external factors. For Brenden Whittaker, a 25 year old from Ohio, the constant trips to the hospital and debilitating nature of an inherited genetic disease made this goal particularly challenging and, for most of his life, out of sight.

Brenden was born with chronic granulomatous disease (CGD), a rare genetic disorder that affects the proper function of neutrophils, a type of white blood cell that is an essential part of the body’s immune system. This leads to recurring bacterial and fungal infections and the formation of granulomas, which are clumps of infected tissue that arise as the body attempts to isolate infections it cannot combat. People with CGD are often hospitalized routinely and the granulomas themselves can obstruct digestive pathways and other pathways in the body. Antibiotics are used in an attempt to prevent infections from occurring, but eventually patients stop responding to them. One in two people with CGD do not live past the age of 40.

In Brenden’s case, when the antibiotics he relied on started failing, the doctors had to resort to surgery to cut out an infected lobe of his liver and half his right lung. Although the surgery was successful, it would only be a matter of time before a vital organ was infected and surgery would no longer be an option.

This ultimately lead to Brenden becoming the first patient in a CGD gene therapy trial at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center.  The trial, lead by UCLA’s Dr. Don Kohn thanks to a CIRM grant, combats the disease by correcting the dysfunctional gene inside a patient’s blood stem cells. The patient’s corrected blood stem cells are then reintroduced, allowing the body to produce properly functioning neutrophils, rebooting the immune system.

It’s been a little over three years since Brenden received this treatment in late 2015, and the results have been remarkable. Dr. David Williams, Brenden’s treating physician, expected Brenden’s body to produce at least 10 percent of the functional neutrophils, enough so that Brenden’s immune system would provide protection similar to somebody without CGD. The results were over 50 percent, greatly exceeding expectations.

Brenden Whittaker mowing the lawn in the backyard of his home in Columbus, Ohio. He is able to do many more things without the fear of infection since participating in the trial. Photo courtesy of Colin McGuire

In an article published by The Harvard Gazette, Becky Whittaker, Brendan’s mother, is quoted as saying, ““Each day that he’s free of infection, he’s able to go to class, he’s able to work at his part-time job, he’s able to mess around playing with the dog or hanging out with friends…[this] is a day I truly don’t believe he would have had beyond 2015 had something not been done.”

In addition to the changes to his immune system, the gene therapy has reinvigorated Brenden’s drive for the future. Living with CGD had caused Brenden to miss out on much of his schooling throughout the years, having to take constant pauses from his academics at a community college. Now, Brenden aims to graduate with an associate’s degree in health sciences in the spring and transfer to Ohio State in the fall for a bachelor’s degree program. In addition to this, Brenden now has dreams of attending medical school.

In The Harvard Gazette article, Brenden elaborates on why he wants to go to medical school saying, ” Just being the patient for so long, I want to give back. There are so many people who’ve been there for me — doctors, nurses who’ve been there for me [and] helped me for so long.”

In a press release dated February 25, 2019, Orchard Therapeutics, a biopharmaceutical company that is continuing the aforementioned approach for CGD, announced that six patients treated have shown adequate neutrophil function 12 months post treatment. Furthermore, these six patients no longer receive antibiotics related to CGD. Orchard Therapeutics also announced that they are in the process of designing a registrational trial for CGD.

Stem Cell Profiles in Courage: Brenden Whittaker

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Brenden Whittaker: Photo Colin McGuire

It’s not often you meet someone who says one of their favorite things in the world is mowing the lawn. But then, there aren’t many people in the world like Brenden Whittaker. In fact, as of this writing, he may be unique.

Brenden was born with severe chronic granulomatous disease (x-CGD), a rare genetic disorder that left him with an impaired immune system that was vulnerable to repeated bacterial and fungal infections. Over 22 years Brenden was in and out of the hospital hundreds of times, he almost died a couple of times, and lost parts of his lungs and liver.

Then he became the first person to take part in a clinical trial to treat x-CGD. UCLA researcher Don Kohn had developed a technique that removed Brenden’s blood stem cells, genetically re-engineered them to correct the mutation that caused the disease, and then returned those stem cells to Brenden. Over time they created a new blood system, and restored Brenden’s immune system.

He was cured.

We profiled Brenden for our 2016 Annual Report. Here’s an extended version of the interview we did with him, talking about his life before and after he was cured.

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Brenden with a CIRM Game Ball – signed by everyone at CIRM

Brenden’s story:

I still think about it, my disease, every few days or so and it’s weird because in the past I was sick so often; before this year, I was sick consistently for about 5 years and going to doctor’s appointments 2 or 3 times a week and being in the hospital. So, it’s weird having a cough and not having to be rushed to the ER, not having to call someone every time the smallest thing pops up, and not having to worry about what it means.

It’s been good but it’s been weird to not have to do that.  It’s a nice problem to have.

What are you doing now that you didn’t do before?

Cutting the grass is something I couldn’t do before, that I’ve taken up now. Most people look at me as if I’m crazy when I say it, but I love cutting grass, and I wasn’t able to do it for 22 years of my life.

People will complain about having to pick up after their dog goes to the bathroom and now I can follow my dog outside and can pick up after her. It really is just the little things that people don’t think of. I find enjoyment in the small things, things I couldn’t do before but now I can and not have to worry about them.

The future

I was in the boy scouts growing up so I love camping, building fires, just being outdoors. I hiked on the Appalachian Trail. Now I’ll be able to do more of that.

I have a part time job at a golf course and I’m actually getting ready to go back to school full time in January. I want to get into pre-med, go to medical school and become a doctor. All the experience I’ve had has just made me more interested in being a doctor, I just want to be in a position where I can help people going through similar things, and going through all this just made me more interested in it.

Before the last few months I couldn’t schedule my work more than a week in advance because I didn’t know if I was going to be in the hospital or what was going on. Now my boss jokes that I’m giving him plans for the next month or two. It’s amazing how far ahead you can plan when you aren’t worried about being sick or having to go to the hospital.

I’d love to do some traveling. Right now most of my traveling consists of going to and from Boston (for medical check-ups), but I would love to go to Europe, go through France and Italy. That would be a real cool trip. I don’t need to see everything in the world but just going to other countries, seeing cities like London, Paris and Rome, seeing how people live in other cultures, that would be great.

Advice for others

I do think about the fact that when I was born one in a million kids were diagnosed with this disease and there weren’t any treatments. Many people only lived a few years. But to be diagnosed now you can have a normal life. That’s something all on its own. It’s almost impossible for me to fathom it’s happening, after all the years and doctor’s appointments and illnesses.

So, for people going through anything like this, I’d say just don’t give up. There are new advances being made every day and you have to keep fighting and keep getting through it, and some day it will all work out.


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