UM stem cell research lifts hope for Alzheimer's patients


Pioneer Founding member
Kim Kozlowski, The Detroit News Published Nov. 18, 2018

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Ann Arbor — For nearly a year, Eva Feldman visited her mother and three other women during dinner at a memory care facility not far from her home. While her mother was capable of feeding herself, one of the other women wasn't.

So during her visits, Feldman helped the woman eat while trying to engage the others in conversation.

Feldman — a University of Michigan researcher and neurologist — kept up that routine until her mother died in March at the age of 89.

During the last months of her mother's life, Feldman observed nearly two dozen people living at the facility and witnessed the symptoms of those with brains succumbing to Alzheimer's disease: some couldn't talk, recognize their family or even remember their own names.

"It was remarkable as a neurologist to live Alzheimer’s disease," Feldman said. "Their degree of impairment was so profound it made me realize that I needed to do something for this disease if I could and do something as quickly as I could."

That's why Feldman, best known for her pioneering research using stem cells with patients with amyotrophic lateral sclerosis — Lou Gehrig's disease — began working in her lab with stem cells to explore their potential for treating Alzheimer's disease.

Though the work had been underway before Feldman's mother started to fail, it is on the fast track — and it is showing promise.

A paper published last month inNature Scientific Reports showed that implantation of neural stem cells into the brains of mouse models improved recognition and spatial memory, along with learning.

"We can return those Alzheimer mice back to normal cognition with the stem cells," Feldman said. "Our ability to use neural stem cells as a means to improve cognition in Alzheimer's disease models is an amazing breakthrough.

""I'm really hopeful because it is not an orphan disease but it's a disease that is experiencing an epidemic in the United States."

The research is three to five years away from a clinical trial but the use of stem cells in Alzheimer mice models landed Feldman's lab a $3 million grant last month from the National Institute on Aging to continue the work.

“We’re very excited seeing that this approach could impact memory and learning in a model of the disease,” said Lisa McGinley, a UM assistant professor in neurology and lead author of the study in Feldman's lab. ‘We’re hopeful this could translate into a patient at some point.”

It is one of many research projects underway around the globe in the battle against Alzheimer's disease, the sixth leading cause of death in the U.S. More than 5.7 million people are living with the disease, costing $277 billion a year, according to the Alzheimer's Association.

The organization calls it a crisis since nearly 14 million are projected to be afflicted with the brain-wasting disease by 2050 and costs to care for the population could reach $1.1 trillion.

There is no cure for Alzheimer's; treatment typically focuses on maintaining, managing or slowing the disease, according to the National Institute on Aging.

Advocates are hopeful as volunteers educate lawmakers and lobby them to prioritize increased funding for research. Over the past five years, federal research funds have quadrupled including $425 million set aside for Alzheimer's this year, said Jennifer Howard, executive director of the Michigan Great Lakes Chapter of the Alzheimer's Association.

"Our vision is a world without Alzheimer’s," said Howard. "Our ultimate mission is to eliminate the disease through the advancement of research."

The Alzheimer's Association convenes researchers from around the world at its international conference to encourage them to discuss ideas and work together.

At the group's 2018 gathering in Chicago, Howard said many important research projects were presented, including a blood pressure management study that showed significant risk reduction and even cognitive improvement in people with mild impairment when their systolic number was kept at 120 or below.

There also have been "monumental" breakthroughs in recent years, Howard added. She pointed to more advanced brain imaging that can show what is happening in the brain.

"We’re able to see amyloid (plaque) build up and tau," said Howard, referring to substances in the brain responsible for Alzheimer's disease. "It has opened the door to research happening with people before they are even showing symptoms because we know a lot of the changes that are happening in the brain are occurring up to 20 years before symptoms start appearing."

The Alzheimer's Association is also supporting studies examining prevention and lifestyle, including exercise, diet and social activities.

"We feel that the answer is probably a combination of intervention," Howard said. "And that may be more like a cocktail intervention that we see with HIV AIDS ... or lifestyle changes and intervention, much like you see with heart disease."

As for the work coming out of Feldman's lab involving stem cells, Howard said the organization has not seen any breakthroughs involving stem cell research but she was excited by the results at the University of Michigan.

"The Alzheimer's Association is excited about any hope and promise," Howard said.

The UM research involved the injection of stem cells into the mice's hippocampus, the brain's memory and learning center. Researchers performed tests on the mice after injecting the stems cells into their brains and found improvements in various types of memory, said McGinley.

Four weeks after the stem cell transplants, the mice showed improved short-term recognition memory. Sixteen weeks after the transplants, the mice showed improved spatial learning.

"These models also showed reduced amyloid plaques," McGinley said. "This was reduced in the mice that got the stem cell injections."

"We're really hopeful this could help," McGinley said. "We are so interested in stem cells compared to drug therapies because most drug therapies don’t really have as much of an effect right now for patients, unfortunately. The stem cells work in so many ways."

The next step in the research, Feldman said, will involve taking the research from a small animal and showing that it is safe in a larger animal, with the hope of taking this to a clinical trial.

Unlike the ALS clinical trial, where new technology had to be developed to deliver the stem cells, Feldman said existing technology can be used in the Alzheimer's work.

"It's a really meaningful advance," Feldman said. "There is an epidemic of Alzheimer's disease. And there is no effective treatment. This brings hope."

Henry Paulson, director of UM's Michigan Alzheimer’s Disease Center, said the most interesting thing about the study is that "this injection of stem cells is probably not replacing lost neurons but rather likely boosting an inflammatory response in the brain."

"That itself may be highly beneficial," Paulson said.. "Lots of scientists (are) interested in boosting inflammatory pathways as a way to make a dent in this disease."

He added that the Feldman's study is still only a small step.

“While researchers have learned a tremendous amount about the causes of Alzheimer’s, we still don’t know which avenues are going to lead to effective therapies," Paulson said.

"Many roads have failed so far. This intriguing study in a mouse model of Alzheimer’s suggests stem cell treatment may be beneficial, perhaps by boosting a microglial response. Preventing disease in mice is still a long step from therapy in humans, but it is a promising step toward treatment for people affected by this disease.”

People whose families have been touched by Alzheimer's, such Lauren Kovach of Brighton, say they are excited to hear about new developments, especially those coming out of local research institutions.

Years ago, when Kovach was caring for her grandmother, a social worker at the Alzheimer's Association told her something she never forgot.

"You have to mourn that person every day and yet they are sitting right next to you," Kovach said. "It is the most devastating disease to watch because there is absolutely no hope. You slowly watch that person die in front of you. And many people are living longer with it, So it can be years and years ..."

Any new breakthrough, Kovach said, will help.

The Alzheimer's Association has a 24-hour line for anyone in search of help: 1-800-272-3900.