UM researcher uses stem cells to fight Alzheimer's

Kim Kozlowski
The Detroit News

To study Alzheimer’s, UM neurosurgeon Osama Kashlan sets up a system to perform surgery on mice to inject stem cells.

Ann Arbor — Inside a laboratory at the University of Michigan, researchers have been injecting stem cells into the brains of mice engineered to have Alzheimer's disease, and making remarkable discoveries.

The experiments are among the first in the nation to examine how stem cell therapies might alter the course of Alzeheimer's, a fatal disease that afflicts more than 5 million people in the U.S. and is widely regarded as an epidemic predicted to explode as the nation's population ages.

The research is being overseen by UM's Dr. Eva Feldman, who pioneered the nation's first clinical trial using stem cells in patients with amyotrophic lateral sclerosis — a disease that received global awareness last summer thanks to the ALS ice bucket challenge.

Dr. Feldman

While Feldman's ALS trial is not complete, it is showing promise. That's why she began an experiment to see how stem cells might fare in treating Alzheimer's disease, another neurodegenerative disorder.

Although it's very early in the research, the Alzheimer's experiment with mice showed that stem cells made a mouse with Alzheimer's disease indistinguishable in behavior and memory from a mouse that didn't have the disease.

"When you work in science, you do as many experiments that don't work that do," Feldman said. "When you get something that works so beautifully (like this experiment), you can quickly see its translational potential. I am looking at a mouse but some day I could be looking at a man. As a clinician scientist, those are the moments you live for."

The findings from Feldman's preclinical trial were presented last month in Boston at the Congress of Neurological Surgeons annual meeting.

While some experts are cautiously optimistic, others hailed Feldman's work.

"The special design of the present study sets new standards for further clinical translation in regenerative medicine for neurological diseases," Tamir Ben-Hur, a Jerusalem-based neurology professor, wrote earlier this year in the Annals of Neurology. "This study design represents the best moral solution for the difficult task of testing risky procedures in a deadly disease with no alternative therapy or hope."

Feldman, a UM professor and neurologist, began testing stem cells years ago. Her research began with rats and pigs with ALS — also known as Lou Gehrig's disease — before she launched a clinical trial in humans with the disease five years ago.

Last year, some participants in the human study either improved or stabilized in the closely watched clinical trial.

Soon after, the Alzheimer's study was launched. That study used fetal stem cells provided by Neuralstem Inc., a Maryland company. It used mice that had been engineered with the inherited gene of Alzheimer's but had not yet displayed symptoms.

With one group of the mice, UM researchers injected the stem cells into the hippocampus, the area of the brain that controls learning and memory. Another group of mice were injected with saline solution. The mice that got the stem cells were evaluated with several behavioral and memory tests — and looked the same as mice without Alzheimer's disease.

"Those animals retained their ability to think, as a mouse does, to recognize objects so they looked just like an animal that doesn't have Alzheimer's disease," Feldman said. "It's really remarkable."

Feldman is still deciding which larger animal model to use for further research, but her associates say it likely will be rhesus monkeys.

"She's doing stuff that needs to be done," said Robert Karbel, manager of the Sinai Medical Staff Foundation in Southfield, a group of physicians that has supported Feldman's research with $500,000. "She has the courage to do it ... and she seems to be making progress. There are no cures yet, but she's working at it."

Feldman's latest study is generating excitement because if successful, it has the potential to impact millions of lives. About 5,600 people are diagnosed with the disease each year, according to the ALS Association, but Alzheimer's afflicts 100 times more people, not counting their family caregivers.

Alzheimer's is a fatal disease with no cure and no meaningful agents to delay its course. The disorder slowly robs people of their ability to remember and perform daily tasks, which is why so many end up in long-term care facilities.

As the baby boomer population ages, many regard Alzheimer's as a tsunami that could swamp the nation's health care system if a better intervention is not discovered, in part because of how costly it is to care for its victims.

In 2014, the direct costs to care for those with Alzheimer's will total an estimated $214 billion, including $150 billion in Medicare and Medicaid costs, according to the Alzheimer's Association.

By 2050, those costs are expected to soar to an estimated $1.2 trillion.

There are all kinds of studies — nearly 50 — in various stages of research to address the disease. But Feldman is among the first to examine stem cells, according to Dr. Keith Fargo, director of scientific programs and outreach at the Alzheimer's Association.

Fargo said the research is very preliminary, and should be regarded cautiously. But he also said it is intriguing.

"We think all kind of research is needed," Fargo said. "We support a full-court press in Alzheimer's disease research."

For people like Ted Harada, the research is more personal. Harada, 42, of McDonough, Ga., was in the first phase of Feldman's ALS trials, shortly after he was diagnosed with ALS in 2011.

He received millions of stem cells in his spinal cord in two separate surgeries.

By his doctor's predictions, he could have already lost his battle to the disease. Instead, he no longer uses a cane and has stabilized.

"We've all heard for years that stem cells could be the next big frontier in medicine," Harada said.

"It's great they are finally allowing these type of trials and I am so thankful researchers like Dr. Feldman are on the front lines pushing the envelopes and not accepting the status quo. Her research is giving hope to communities where hope was an absent commodity."

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