Desperate for a Cure, Part 4
7:00 am
Thu October 3, 2013

Advances in Alzheimer's Diagnosis, But Where Are the New Drug Therapies?

Alzheimer's researcher Bill Klunk, in his lab at the University of Pittsburgh, where he led the development of a new brain scanning compound that can see Alzheimer's-related pathology in the brain.
Alzheimer's researcher Bill Klunk, in his lab at the University of Pittsburgh, where he led the development of a new brain scanning compound that can see Alzheimer's-related pathology in the brain.
Credit Photo by Sean Corcoran

Part 4 of our 5-part series "Desperate for a Cure: The Search for New Alzheimer's Treatments."    

Dr. Bill Klunk is a clinician and researcher at the University of Pittsburgh, and he spent much his career finding ways to see Alzheimer's in people's brains.  

Sometimes, he said, he likes to tell people about his dream last day on the job -- that final day before he retires. And in the dream, he meets with Mrs. Smith in the clinic and he says:

"You know, your testing does show some mild problems, you know, can't be sure. It might be something, it might not. We'll do some amyloid imaging and see if there's pathology in the brain."

In this dream, they do the scan, and things might look good, so he comes back to Mrs. Smith and says:

"Maybe this is just depression or anxiety or a bad night's sleep."

Or, maybe in this fantasy, they do the scan, and they see the known Alzheimer's protein amyloidBeta building up in Mrs. Smith's brain. So, Dr. Klunk says, 'don't worry,':

"We have a drug to treat it. We have a method to see if that drug is working for you. And if the dose doesn't work for you we can change it until it does work, like giving you a high blood pressure medication and monitoring your blood pressure. And you'll probably live a long and happy life long before this Alzheimer's stuff becomes meaningful to you. That's what I'd like to do, last day, close the door, feel good about my role in the imaging development, and go home."

There is no such drug yet. And Klunk related this daydream in his office, surrounded by mounted freshwater fish, and drawings of freshwater fish, and happy sayings on small signs about catching freshwater fish. Here, it's easy to imagine that Klunk probably would enjoy his retirement days -- fishing.

"But, I don't think I'm going to be having that day for a little while yet," he said.

When it comes to new Alzheimer's drugs, the most recent thinking is that it's important to get them into people early -- even before symptoms -- in order to stop that AmyloidBeta from building up in the brain. It's the Amyloid that's known to turn toxic, and eventually glob together and form Alzheimer's tell-tale plaques. Amyloid buildup is one of the earliest things known to happen in the course of the disease.

But to test these new drugs, researchers need to do two things: they need to see the amyloid in the brain to determine who should be involved in a drug study. And once a study starts, they need to the scan the brain on a regular basis to gauge if the drugs are working.

So in the 1980s and 90s, as some researchers searched for drugs to prevent amyloid buildup, Klunk and his colleagues got to work on the brain imaging. And they found success.

"What we thought we would have now in 2013," he said, "as we were doing the first human studies and seeing the nice results in 2002, was an anti-amyloid agent that would modify the disease process. As of yet we have no disease drug in that category. So the imaging technology has important uses, but it really is, I think, is best described as sitting there waiting for its therapeutic partner."

Still, it's worth knowing that with improved testing in the doctor's office, combined with the new brain scanning techniques, the days of not being able to accurately diagnose Alzheimer's except in an autopsy, are mostly gone.

"Now we have a clinically approved amyloid imaging agent," he said. "If a doctor suspects their patient of having memory loss do to Alzheimer's disease they can imagine the agent in the brain to see if it's there, and if it's not there, you can be pretty certain those symptoms are not due to Alzheimer's."

In the Alzheimer's world, Klunk is something of a legend because he played a key role in developing what's called the Pittsburgh Compound -- a radioactive dye that shows amyloid in the brain during scans. The compound is chemically similar to curcumin, which essentially is a spice in turmeric. And one of the reasons it works so well is because it gets through the membranes that surround and protect the brain, called the blood-brain barrier.

"Our life is a battle with the blood brain barrier when you're trying to image anything in the brain," he said. "The brain doesn't trust you to put the right things into your mouth or wherever you inhale it or whatever. So it reserves right of first refusal of anything that shouldn't be in it."

Klunk and his team were able to build upon previous work, and get their curcumin-like compound past the blood brain barrier. The compound was a major advancement in research.

But some Alzehimer's doctors are frustrated. Last month, federal government decided that it will not pay to scan suspected Alzheimer's patients, unless the scans being used to see if someone is a good candidate to participate in a drug trial.

Dr. Samuel Gandy of the Mount Sinai School of Medicine in New York, said wider use would give researchers more information about the disease, and there's value, he said, in affirming the diagnosis people get in their doctor's office.

"These things," he said, "they have an educational value for the public who still see diseases like Alzheimer's as mysterious and perhaps the public would be more supportive if they understood what they were doing, that now we have a scan, we can see the disease, and now we are developing drugs to treat it. That strikes me as a good thing, but I can't prove to Medicare it has a dollar benefit for them."

Gandy and Klunk, they know how important their research is. The number of people with Alzheimers is rapidly increasing -- with 16 million expected to have it by the year 2050. If a way to effectively treat and delay Alzheimer's is not found soon, the nation will have to make some hard choices, Klunk said -- either reduce care for patients to save money, or let the economy self destruct.

"We need people to know what a terrible, impending problem is facing us," he said. "People who have seen the disease know how horrible it is. They may not fully appreciate the numbers that are in the wings, who already have pathologies in the brain as we sit here, maybe 10, 15 years ahead of their first symptoms. It's already amongst us."

Finding a cure or preventative for Alzheimer's will be expensive. Drug trials are costly, and Klunk said they'll become even more so, as most new, experimental Alzheimer's drugs will need to be monitored for a long time -- a year and a half, two years, or more -- to even see if they're working. So that's years of expensive drugs and brain scans at $3,000 or $4,000 a scan. But, Klunk said, if we don't spend that money now, we certainly will pay for it in the future.