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How these breakthrough drugs to fight Alzheimer’s disease rely on Columbus Memory Center

When the researchers at Columbus Memory Center first began, they had to ask companies to let them participate in drug trials.

Today, they have to turn down pitches.

But a pair of trials they did not turn their backs on now has it as a significant partner in running inclusive clinical trials of two breakthrough drugs that are aimed at slowing cognitive decline in Alzheimer’s patients. And a big part of its success are the Columbus residents who volunteered for the trials.

Lecanemab, marketed as Leqembi, is owned by pharmaceutical companies Essai and Biogen. The drug is expected to be formally approved by the U.S. Food and Drug Administration in early July.

The center is also participating in the clinical trial for another drug from Eli Lilly called donanemab, which does not yet have an assigned brand name.

By developing Leqembi and donanemab, researchers have begun to crack the code of Alzheimer’s Disease, said Dr. Jonathan Liss, a neurologist, subspecialist in memory disorders and founder of the Columbus Memory Center.

“We’ve got a long way to go still,” Liss said. “But in 20 years we’ve not had a major breakthrough. And of all the breakthroughs we’ve had, this is the most important.”

Both of the drugs have been shown to be effective in cognitive decline, he said, and Liss is confident that they will both be approved by the FDA in time.

Dr. Jonathan L. Liss, M.D., is the founder, the primary physician, and director of the Columbus Memory Center in Columbus, Georgia. 05/25/2023
Dr. Jonathan L. Liss, M.D., is the founder, the primary physician, and director of the Columbus Memory Center in Columbus, Georgia. 05/25/2023

Importance of participation

Liss takes pride in bringing this Alzheimer’s research to Columbus, he said, because it means people in the city are getting the same research opportunities as the most important universities in the world.

“They’re getting the same care as if they live next door to Johns Hopkins,” he said.

In 1996, Liss and his colleagues started general research in Columbus in a separate legal entity, he said. By 2012, the organization decided to focus on Alzheimer’s research and became what is currently known as the Columbus Memory Center in 2019.

Over the last three decades, the center has established itself as a renowned research facility that now receives frequent pitches for trials, Liss said.

The center examines the science behind trials and makes sure they have the right patient population for a successful trial, he said. But the success of the center is dependent on residents in Muscogee County being willing to participate, he said.

The help of former Mayor Teresa Tomlinson, Mayor Skip Henderson and the city council were instrumental in helping the Columbus Memory Center spread the message and encouraging people to participate, Liss said.

“For the (drug) that’s coming soon, Leqembi, we were number three in the entire country in enrollment for this,” he said. “We beat out all the big places like Johns Hopkins, Mayo Clinic, Emory University and UCLA.”

Inclusivity brings more clinical trials to Columbus

The Columbus Memory Center worked with local officials and the Georgia chapter of the Alzheimer’s Association to ensure that clinical trials run at the center are inclusive, he said.

It’s important that minority groups are included in the research, Liss said, so researchers can be confident in saying that a drug works for people of all ethnic backgrounds. The memory center has made an effort to go out into the community to ensure participants in the trials are diverse, he said.

“If you look at the data, in one of the trials that we did, we had 20 times greater opportunity for minorities to be involved in the trial then the general average across the nation,” Liss said. “ And for Leqembe, we had five times greater participation than the rest of the nation.”

Dr. Jonathan L. Liss, M.D., is the founder, the primary physician, and director of the Columbus Memory Center in Columbus, Georgia. 05/25/2023
Dr. Jonathan L. Liss, M.D., is the founder, the primary physician, and director of the Columbus Memory Center in Columbus, Georgia. 05/25/2023

One important factor in the success of ensuring more marginalized communities participated in the trials for the drugs is acknowledging past injustices that made people hesitant to begin with, he said.

The Tuskegee Study, a study that involved researchers giving Black men syphilis without their knowledge, resulted in marginalized communities being reluctant to participate in clinical trials, he said. But the experiment resulted in regulations that made trials like the ones run at the Columbus Memory Center safer and more ethical.

“We have put safeguards in place,” Liss said. “So the people like me could never be the people of yesteryear. There are multiple agencies that oversee everything I do.”

As a result, the Alzheimer’s Association has given them a grant so that the Columbus Memory Center may teach others running trials its strategies for reaching minority populations. Despite the center’s success, Liss said, there is still room for improvement.

Their participation rate among minority groups is about 25%, he said, but these groups make up just over 50% of the population in Columbus.

“We’re proud that we’re better than everybody else,” Liss said. “But we have a lot of work to do because we want to get the other half, so that we’re really representing everybody fully.”

How the Alzheimer’s drugs work

Leqembi and donanemab are more similar than they are different, Liss said.

The drugs are injected through the veins, he said, and eventually they could be given as an injection similar to what diabetics use. Once they’re in a person’s system, the drugs go to the brain.

“I think that’s the first medical miracle — when it goes to the brain,” Liss said. “It doesn’t grab onto all the tissue around there. It doesn’t grab onto a neuron. It goes after the thing we don’t want in the brain called beta-amyloid.”

Beta-amyloid is a protein that can clump together to form plaques found in the brain tissue of Alzheimer’s patients. The drugs attach to the protein and become like a “homing pigeon” for the immune system, Liss said.

“The immune system comes in and takes that protein out of the brain and eliminates it almost like a vacuum cleaner,” he said. “And that’s the difference that gets made that seems to be slowing down the disease.”

Leqembi is intended for patients who are on the pathway towards the disease, but don’t have it, Liss said, or people in the early stages of the disease. The drugs can theoretically add another five to six years of indepence to a person’s life, he said.

“For that 85-year-old, that gets them to 91,” he said. “Frankly that’s a cure. So, that’s a very exciting thing, and about half of the patients are 85 and above.”

Researchers still have a long way to go in treating Alzeiher’s, Liss said. Although another five to six years are important, they have less of an impact on younger patients in the 50’s or 60’s.

“Young and old will get this drug,” he said. “But we’re going to need more than this for the younger people in order to maintain their independence at home.”

Along with not having as significant an impact on younger patients, Liss said, Leqembi can cause bleeding or swelling in the brain for some people.

The drug may cause microhemorrhages, he said, which are little dots of blood that don’t seem to cause real harm. The swelling occurs when the immune system removes the protein from the brain.

Most of the people who experience the side effects have no idea they’ve occurred until they’re told about it, Liss said.

“They are almost always modest side effects, like a headache or feeling a little off balance,” he said. “And then they’re the rarest of circumstances.”

Ultimately, it’s up to the memory center to have conversations with everyone about how the drug may affect them, Liss said, so patients are fully informed.

“I would take it in a second myself,” he said. “And I would give it to my family members if they needed it.”