Stem cells for Alzheimer's?

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Stem cells for Alzheimer's?

June 11, 2004

Approach unlikely to yield cure for the disease, experts say, although

some look to endogenous stem cell manipulation | By Anne Harding

The death of former US President Reagan Saturday (June 5) after a

decade-long struggle with Alzheimer's disease-just a month after former

First Lady Reagan spoke publicly for the first time in support of

stem cell research-has firmly linked stem cells with the hope for an

Alzheimer's cure in the public mind. But most in the field admit it's

highly unlikely that a stem cell transplant could cure or even treat

Alzheimer's.

" Alzheimer's is a tough target for this sort of thing because it is

widespread and it involves so many different types of neurons, "

L. Price, director of the Alzheimer's Research Center at s Hopkins,

told The Scientist. " There are other diseases, like Parkinson's, which

may be much more amenable to stem cell therapies. "

It's a matter of taking a " very narrow view or a large view, " said Sam

Gandy, vice chair of the National Medical Scientific Advisory Council of

the Alzheimer's Association and director of the Farber Institute for

Neuroscience at Jefferson Hospital in Philadelphia. Lessons that

can be learned from stem cell transplants for Parkinson's and other

types of neurodegenerative disease will reveal a great deal about cell

signaling and cell environment that could be applied in Alzheimer's,

Gandy said.

Shelanski, codirector of the Taub Institute for Research on

Alzheimer's Disease at Columbia University, said he and his colleagues

are developing drugs that would fight the degenerative disease by

strengthening the synapse. Other groups are looking at ways to block

gamma secretase and beta secretase. But over the long term, the stem

cells already found in the brain offer the most intriguing potential,

Shelanski and others said.

In fact, argued Mark Mehler, stem cells offer the only real hope for

repairing the damage Alzheimer's does to brain cells and cellular

connections built up over a lifetime.

" Our ability to repair damage to the nervous system has to be focused on

not just giving back the cells that have died, but giving them back in a

way that allows them to incorporate " into neural networks, Mehler, who

directs the Institute for Brain Disorders and Neural Regeneration at the

Albert Einstein College of Medicine in the Bronx, told The Scientist.

" We have to supply them in the way that they were originally generated

during development through activation and maturation of endogenous adult

stem cells from brain regions adjacent to the sites of irrevocable cell

injury and death. "

Over the past 2 years, Mehler and his colleagues have found increasing

evidence that the process that leads to cell death in Alzheimer's

actually begins during early embryonic development, suggesting that such

vulnerable cells could be repaired with gene therapy or even replaced by

stem cells.

The former first lady's May 9 speech was her first public statement on

stem cell research, although her views have been known for some time.

The day before Reagan's death, a bipartisan group of 58 senators sent a

letter to President Bush urging him to allow federal funds for research

on donated surplus embryos created by in vitro fertilization. A group of

congressmen sent a similar letter to the president this April, and

received what some considered a promising response from NIH Director

Elias Zerhouni.

If the wave of support driven by Reagan's death does lead to a shift in

Bush Administration policy, " it would be a terrific boon to the field "

of Alzheimer's research, said Fred Gage, professor in the Laboratory of

Genetics at the Salk Institute in San Diego. Embryonic stem cells could

be engineered to express the genetic defects known to lead to

Alzheimer's, he said, which would offer a molecular and cellular window

into the course of the disease and could also be used to screen

compounds.

Using stem cells to replace a particular type of neuron " is something

that should be kept on the horizon, " said Gage, " but as an immediate

application is hard to fathom. "

A researcher who has used stem cell transplants in mice with

Alzheimer's-like memory loss to improve the animals' performance in a

maze is more upbeat than most about the potential of stem cell

transplants for human disease. " I do believe stem cells can do many

things for Alzheimer's, " Kiminobu Sugaya, a professor at the University

of Central Florida, told The Scientist.

One major hurdle, according to Sugaya, would be to downregulate the

production of amyloid precursor protein in the brain before

transplanting stem cells. Sugaya has done research suggesting that the

protein has some physiological function in the normal brain, so he is

reluctant to block it entirely. Then, he said, researchers could work

toward using stem cells to replace the basal forebrain cholinergic cells

that are the first to die in Alzheimer's. " It could be difficult, but I

think we can figure out how to make it happen, " Sugaya said. Also, he

noted, it would be " easy " to replace the intramural cells in the cortex

that degenerate in Alzheimer's with stem cells.

Though most in the field see this strategy as unrealistic, " one always

hopes to be surprised, " said Price.

http://www.biomedcentral.com/news/20040611/04

I'll tell you where to go!

Mayo Clinic in Rochester

http://www.mayoclinic.org/rochester

s Hopkins Medicine

http://www.hopkinsmedicine.org