Neural Stem Cell Therapy

[Guest guest]

Neural Stem Cell Therapy

http://www.specialchild.com/archives/ia-039.html

In November 1999, Layton BioScience, Inc., a biopharmaceutical

company focusing on developing therapeutic treatments for diseases of

the central nervous system, entered into an exclusive, worldwide

agreement with Children's Medical Center in Boston to join Dr. Evan

Snyder in his research of neural stem cell technology. While this news

may be of little or no importance to most individuals, this newly

formed relationship may actually give rise to what could be the

long-awaited " light at the end of the tunnel " for many parents of

children with inherited neurogenetic disorders, cerebral palsy, spinal

cord damage, brain cancer (tumors), and many other childhood brain

disorders.

What is neural stem cell therapy?

Neural stem cell therapy involves the transplantation of " normal "

working neural stem cells into the brains of those individuals with

damaged or non-functioning cells. When injected, these stem cells

" take-over " where the damaged cells are not functioning and correct

the problems, thereby, providing an effective treatment for a wide

range of disorders.

What studies have been conducted?

The emphasis on neural stem cell technology began in November 1998

when Evan Snyder, M.D., Ph.D., an assistant professor of neurology at

Harvard Medical School, and his colleagues reported that they had

cloned human neural stem cells and that when the cloned cells matured,

they gave rise to both neurons and their support cells (glia). For

many years, transplanting mouse cells into mouse brains has been a

successful approach in treating many disorders, however, lack of human

cells for study has delayed such research to be performed with the

human brain. With the ability to clone human cells, researchers are

now much closer to finding future therapies and treatments for humans,

rather than just their rodent counterparts.

In the 1998 study, scientists were able to remove cells from deep

within the forebrain of an aborted human fetus, clone the sample of

cells, and then transplant these immature stem cells into different

areas of a developing mouse brain. They found that the human stem

cells migrated along pathways that had already existed in the mouse's

brain and then matured into the type of neuron and glia that were

appropriate for the particular area in need.

The scientists then took their research one step further and

applied their newfound technology to a specific disorder. They showed

that enzyme producing stem cells (in culture) were able to take over

and correct the protein deficiency found in Tay-Sachs disease. This

success would confirm the idea that human cells may be able to supply

therapeutic proteins that are missing in inherited brain diseases, and

if so, could then correct inherited disorders.

In June 1999, Dr. Snyder led another study which provided the

first evidence that, from studies in animals, neural stem cells can be

used to repair damage from brain disorders such as adrenoleukodystrohy

and multiple sclerosis, where cell dysfunction is spread throughout

the brain. Prior to this study, it was thought that stem cells would

only be used for disorders that affected a specific portion of the

brain. These latest findings raise exciting possibilities for future

therapies for a myriad of neurological and genetic disorders.

In this particular study, Dr. Snyder injected neural stem cells

from a mutant strain into the brain ventricles of newborn mice, which

caused them to have severe tremors by 2 to 3 weeks of age. The tremors

developed because the mice were lacking the key protein needed to make

myelin, the insulating coating that surrounds nerve fibers. This lack

of myelin in the mice is similar to the defect seen in many human

demyelinating disorders, such as multiple sclerosis and a group of

childhood disorders known as leukodystrophies. The researchers found

that most of the transplanted cells migrated throughout the brain and

matured into normal-looking, myelin-producing brain cells

(oligodendrocytes). In addition, not only did the cells survive, but

they went right to the wounded region, produced a significant amount

of the missing protein, and began to cover nearby fibers with myelin

just as normal oligodendrocytes would. Further, the tremors

disappeared almost completely in 60 percent of the tested mice that

received the transplants.

Researchers also discovered that neural stem cells transplanted

into the brains of the mutant mice were much more likely to form

oligodendrocytes than were neural stem cells transplanted into the

brains of normal mice. This suggests that the neural stem cells

somehow know that something is missing in the mutant mice and attempt

to compensate for the problem.

When will neural stem cell therapy be available?

While neural stem cell therapy is very promising, researchers

still have many issues to address before they can begin clinical

trials with humans. Some of these issues are as follows:

* They need to learn whether older animals will benefit from

transplantation, as have the younger animals.

* They need to learn whether transplanted cells can survive an

ongoing degenerative disease process or whether they too will fall

victim to degeneration, as have their predecessors.

* They need to do follow-up research to better understand how

transplanted cells are directed to grow throughout the brain and

compensate for missing brain proteins.

* They need to determine whether transplanted cells will cause

an immune response in a human host (in rodents, no response was seen).

Dr. Snyder is currently testing neural stem cells in animal models

for many disorders, including perinatal asphyxia (which can lead to

cerebral palsy), Krabbe's disease (a demyelinating disorder), and

stroke. If Dr. Snyder's studies yield positive results, they could

eventually lead to clinical trials. However, it is too early to say

which human disorders might be the first to be targeted with neural

stem cell therapy, and it will take years of careful clinical testing

before researchers can show conclusively whether the stem cells work

in human disease.

Dr. Snyder and Layton BioScience, Inc.'s CEO, Snable, " hope

to one day eliminate a wide variety of acute and chronic neurological

disorders and disabilities. " Dr Snyder comments: " In the actual brains

of a number of animal models of neurological diseases, it's as if the

cells know the injured area is there and how they are needed. Now our

challenge is to make this miracle of science relevant to humans. By

partnering with a company with Layton BioScience, Inc.'s expertise,

resources, vision, and ability to bring cellular and molecular

therapies to clinical trials, we will be able to explore this to the

fullest extent possible. "

References:

* Layton BioScience, Inc. http://www.laytonbio.com

* National Institute of Neurological Disorders and Stroke

http://www.ninds.nih.gov

* Park KI, Liu S, Flax JD, Nissim S, Stieg PE, Snyder EY,

Transplantation of neural progenitor and stem cells: developmental

insights may suggest new therapies for spinal cord and other CNS

dysfunction. Journal of Neurotrauma 1999 Aug;16(8):675-87

* Yandava BD, Billinghurst LL, Snyder EY, " Global " cell

replacement is feasible via neural stem cell transplantation: evidence

from the dysmyelinated shiverer mouse brain. Proceedings of the

National Academy of Sciences, 1999 Jun 8;96(12):7029-34

* Flax JD, Aurora S, Yang C, Simonin C, Wills AM, Billinghurst

LL, Jendoubi M, Sidman RL, Wolfe JH, Kim SU, Snyder EY, Engraftable

human neural stem cells respond to developmental cues, replace

neurons, and express foreign genes. National Biotechnology, 1998

Nov;16(11):1033-9