Innovators Network Support in Action: Dr. Drew Mhyre

Innovators Network Support in Action: Dr. Drew Mhyre

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The Project Violet team at Fred Hutch
Drew Mhyre with daughter Katelyn in the hospital
Dr. Jennifer Mhyre and daughter Katelyn
An optide targets the tumor while barely affecting healthy organs.
Cancer cells dying off when PHF5A production is suppressed
Katelyn, Ashley and Jason Mhyre
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Joining Project Violet

Two things attracted me to the Project Violet team. First, the potential these optides have in treating rare diseases is really unique. [Optides are drug candidates developed from the scaffolds of naturally occurring molecules with a unique balance of medicinal properties.]

Secondly, Jim [Dr. Jim Olson, who leads Project Violet], has a vision for translational medicine that’s really unique in an academic setting. Project Violet uses an inverse pharmacology approach, in which we identify and screen optides for drug-like properties and determine where they go in the body before even knowing if they are efficacious for treating particular diseases. By eliminating optides that don’t get to the target of interest, you really get to focus on those that could work, rather than wasting time with those that may never become a clinically useful drug.

Photo: The Project Violet team at Fred Hutch. Drew is in the long-sleeved white shirt at the right. 

Bo Jungmayer / Fred Hutch

Rare diseases hit home

The potential for developing new treatments for rare diseases is really the driving reason for why I’m here. My daughter Katelyn has a rare disease. When Katelyn was only 12 weeks old, she started having seizures that the doctors considered intractable. No matter what medication they tried, they could not completely stop the seizures, but only reduce them. The doctors labeled her disease as malignant migrating partial epilepsy of infancy, which is very rare. When she was first diagnosed, there were only about 200 documented cases in the world, and the prognosis was pretty grim. We later learned that she also had mitochondrial disease. Her mitochondria [the energy-producing parts of the cell] function at only 3 percent of normal, is what they’ve determined. The doctors now believe that her mitochondrial disease is what is causing the epilepsy.

Photo: Drew with Katelyn in the hospital in 2009. 

Courtesy of the Mhyre family

Hope through research

Until about four years ago, not much effort in the research community was put toward mitochondrial disease. The only treatment was vitamins. But then a company in San Francisco launched a clinical trial of a novel therapy for her disease, and Katelyn was lucky enough to be a participant. When she was diagnosed, the prognosis was that she wouldn’t live to age 5. Last October was her sixth birthday. This clinical trial was life-changing for Katelyn. It has given us more time with her and a renewed hope for the future.

Research is interesting in itself, but I have seen firsthand how it also gives hope to patients and families that nothing else can really give. That’s something that I’d love to give to other families. I have chosen to dedicate my career to exploring rare diseases in hopes of finding cures for pediatric brain cancer and other diseases that have been largely ignored by the pharmaceutical industry. Time is the one thing that every parent wants more of with their child, especially parents who have lost their child to cancer or another disease.

Photo: Katelyn with her mom, Dr. Jennifer Mhyre, around Katelyn’s fifth birthday.

Courtesy of the Mhyre family

Delivering warheads to tumors

Based on the success of the Tumor Paint molecule, we have built Project Violet to explore these amazing little drug candidates called optides. By taking advantage of the same tumor-targeting potential as Tumor Paint, we hope to use molecules with similar properties to chlorotoxin [a component of Tumor Paint that is derived from scorpion venom] to deliver toxic warheads right to the tumors. With Tumor Paint, you can see where the tumor is, but now we’re looking to actually kill the tumor cells. We’re definitely making progress now. Actually, in the next couple weeks we’ll be getting data on some novel optides that I fully expect to show targeting of those warheads into tumor cells.

Photo: An optide targets the tumor (red) while barely affecting healthy organs, making it a good candidate for development into a drug-delivery tool. 

Courtesy of Project Violet

A new drug target

One of the most exciting things in our research right now is a new [potential drug] target that we identified for brain cancers, called PHF5A. The [Project Violet] team found that if they knock PHF5A down genetically, it killed off the cancer cells, whereas the normal cells survived. Using the support from the Innovators Network and other private funding, we developed a model to screen for new inhibitors that would hit this target selectively and kill the cancer. I then applied for a large federal grant incorporating some of our preliminary data, and it was actually just funded. It’s really exciting that the NIH thought it was good enough to give us a couple million dollars to really delve into this as a potential cancer target. We are really hoping that all this work will give us a nice targeted therapy for these kids with brain cancers who really have very few options right now.

Photo: Cancer cells (in green) die off when PHF5A production is suppressed (right). The red and purple arrows highlight some dying cells. 

Courtesy of Project Violet

No child deserves to have cancer

If I had a crystal ball, I would fully expect to see that the research that Project Violet is doing today will result in better tools and treatment options for these kids with brain tumors and other cancers ― whether that is the surgeon seeing exactly where to cut to remove the cancer and leave the healthy tissue, or the oncologist prescribing new medications that can effectively kill the cancer without the debilitating side effects of the drugs that they use today.

Our goal as a team is to discover new and more effective treatments for pediatric brain cancers. No child deserves to have cancer and no parent should ever outlive their child.

Read more stories of Innovators Network support in action.

Photo: The Mhyre kids ― Katelyn, Ashley and Jason ― in 2013.

Courtesy of the Mhyre family