June 2009

Connections - June09 - Melissa Ashlock

Sleep? Not Melissa Ashlock...At Least Not Until There's a Cure

Melissa Ashlock, M.D., vice president of drug discovery, has cycled hundreds of miles for CF patients, showered her colleagues with ideas on how to improve CF care and — most notably — directed the drug discovery efforts of the CF Foundation during the most exciting decade in the history of CF research.

Before coming to the Foundation in 1999, Ashlock worked as a scientific investigator at the National Institutes of Health (NIH), where her research mentors included Francis S. Collins, M.D., Ph.D., co-discoverer of the cystic fibrosis gene. At the Foundation, she used her expertise to lead several highly successful drug discovery and development collaborations, including the project with Vertex Pharmaceuticals, Inc.

Returning to NIH next month, Ashlock spoke with Connections about her 10 years as a part of Team CF.

What led you to work at the Foundation?

I’m really interested in CF, and have been since the first time I saw a CF patient in medical school. I’ll never forget, the pediatric attending physician I was working with licked the hand of patient — a very unusual thing to do — to demonstrate the high salt content in the CF patient's sweat. The child was quite ill, very small, pale and coughing. The experience made me more curious about the disease than anything I had ever read in a medical textbook.

What do you do as Vice President of Drug Discovery?

I work as part of a team, where I do three things. First, I try to identify new ways to discover drugs for CF. Once they’re identified, I work to ensure the Foundation is a part of the discovery process. Second, I manage collaborations that are involved in discovering and developing these potential drugs. Last, I identify possible hurdles our collaborators may encounter in the drug discovery process and develop ways to overcome them.

What’s involved in the drug discovery process?

There are two general ways to discover drugs. One way is “the needle in the haystack” approach — screen hundreds of thousands of chemicals in hopes of finding one that affects the disease you’re trying to fix (in our case, CF). The second approach is to use detailed information about what causes the disease you’re trying to fix (in our case, the faulty CFTR protein) to make or design a drug. This strategy is often called the “target-based approach.” Sometimes a combination of these two approaches is what leads to success.

Why is CF so hard to cure?

CFTR, the key protein associated with CF, has some characteristics that make it a difficult target for drug discovery. In particular, there are two challenges — the protein’s size and its function. CFTR is a relatively big protein, which makes it difficult to work with. In addition, fixing how CFTR works in the cell isn’t easy to do.

How have the lives of people with CF changed since you’ve been at the Foundation?

Before I came to the Foundation, two important drugs were approved for CF, TOBI® and Pulmozyme®. In the 10 years since I've been here, these drugs, along with other treatment strategies, have really changed the standard of care in CF. People have a different view of what they can do with their lives now that they’re able to function better with the help of new therapies. People with CF believe their lives can be relatively normal.

Also, with newborn screening, many CF patients are diagnosed earlier. There’s a lot more focus on getting the available CF drugs to individuals as soon as possible, which should improve health outcomes.

In your mind, what’s the most exciting thing that’s happened at the Foundation in the last 10 years?

Definitely the encouraging results from the VX-770 clinical trials. VX-770 generated statistically significant changes in many of the outcome measures related to CF that we were looking at. The reason that’s so exciting is that it shows that the path we took — using small molecules to treat CF, and all the resources and capabilities we used along the way — is on track! It validates our strategy — that small molecules can correct the underlying cause of cystic fibrosis.

You’re leaving the Foundation to work on a special project with the NIH? What will you be doing?

I’m going to turn my focus to a new initiative at the NIH, which aims to discover and develop drugs for rare and neglected diseases. I’ll be able to apply many of the things I’ve learned at the Foundation about drug discovery and development to other rare and neglected diseases that affect millions of people.

What do you think the future holds for people with CF?

I think the future is bright! It’s bright because of the many therapeutic options for people with CF, and because the Foundation understands that the best therapy isn’t necessarily more and more treatments on top of what CF patients already do, but could be few specific therapies directed at treating the basic defect in CF.

What’s the main thing you’ve learned during your time here at the Foundation?

The most important thing I’ve learned through this whole process is the power of the team. None of the drug discovery efforts I’ve been involved in could have gone anywhere if it weren’t for Team CF. It’s truly been an honor to work with everyone, from the patients to the volunteers, the donors to the scientists. We’re all a part of drug discovery and a collaborative effort to cure this disease.

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