Rebuilding the brain

[Guest guest]

ULTIMATELY, the researchers

hope to grow a

virtually

unlimited amount of human brain

tissue to replace

the

diseased neurons of those who have

suffered strokes,

spinal cord

injuries or other neurological

diseases.

In

as-yet unpublished work underway at

Harvard

Medical

School, the scientists have already

shown that, in

mice

genetically engineered to suffer

from human strokes,

neural stem

cells have an affinity for the area

of brain injury.

Once there,

the cells integrate seamlessly into

the

surrounding

brain tissue, maturing into the type

of tissue

appropriate

for the particular area of the

brain.

" There is lots of wiggle room in the

nervous system,

especially

at the level of stem cells, " says

Evan Snyder, an

assistant

professor of neurology at Harvard

who is leading

the

research. " So we can tap into the

natural plasticity of the

seeds and

exploit them.

" What may already have in our hands

is the universal

donor brain

cell, one that can direct cells to

go where we

want them

to and to do what we want them to. "

Conditions ranging from inherited

defects such as

Tay-Sachs

disease to birth-related oxygen

deprivation to

brain

cancer could one day be treated with

neural stem

cells,

Snyder predicts. And that's not to

mention dementia,

Alzheimer's

disease, Parkinson's disease and

multiple

sclerosis _

meaning there are literally hundreds

of

thousands

of patients who could benefit.

SEEDING THE

LAWN

Snyder compares the diseased brain

to a trampled

lawn _

" perhaps a lawn that didn't grow

right or was

destroyed b

the kids biking or by the weather. "

Just as you

would grow

new grass by seeding the lawn, you

can sprout

healthy

tissue by seeding the " broken " brain

_ with neural

stem cells.

Moreover, the stem cells can be

genetically engineered

to grow

super-seeds that produce a gene that

is missing in

the brain,

for example. In other words, you can

isolate and

harvest

neural stem cells and use them as

just as they are, or

introduce

foreign genes through designer

engineering,

tailoring

the treatment to the problem.

And

that is just what happened in mouse

and animal

studies. In

one experiment, for example, his

team removed

stem cells

from deep within the forebrain of a

fetus several

years ago.

When they cloned individual cells,

they gave rise

to both

neurons and their support cells, the

glia.

Then, they grafted immature stem

cells into different

areas of

the developing mouse brain.

Following signals from

their new

environment, the human stem cells

migrated along

existing

pathways and matured into the type

of neuron and

glia

appropriate for the particular area.

To

produce the super-seeds, the

researchers then

inserted

the gene that codes for the protein

that is missing in

patients

with Tay-Sachs disease. In test-tube

experiments,

the

designer stem cells were able to

correct the deficiency

underlying

the genetic disorder, suggesting

that the

super-seeds

could indeed supply therapeutic

proteins

missing in

inherited brain diseases.

In

another test, failing brains in

mutant mice were

shored up

by injecting neural stem cells to

replace damaged

or diseased

cells, he said.

" The

findings prove that the brain is

more like plastic

than we

ever imagined, " the Boston

researcher said.

Questions still remain. While, in

all the experiments, the

grafted

cells integrated seamlessly into the

surrounding brain

tissue, it

remains to be seen if they actually

function.

GOAL CLOSER

TO REALITY

Nevertheless, scientists at the

recent meeting of the

American

Association for the Advancement of

Science in

Anaheim,

Calif., expressed optimism about the

new work.

The

approach brings the goal of

harnessing neural stem

cells for

the treatment of human disease one

step closer to

reality,

says Mark H. Tuszynski of the

University of

California,

San Diego, whose is utilizing other

genetic

engineering

techniques to fight Alzheimer's

disease. " We're

beginning

to see that we can tailor cells and

orchestrate. We

can

recreate the brain. "