June 6, 2007

Nuclear Transfer Strategy Shows Promise for ALS Drug Screening

Roberta Friedman, Ph.D., Research Department Information Coordinator

[Quick Summary:  Researchers may have come up with a new cell source to allow stem cells to take on the characteristics of a disease, an approach with promise for ALS drug discovery.]

Research reported in this week’s Nature suggests a possible new way to tap into the potential of stem cells for drug discovery. Harvard investigator Kevin Eggan, Ph.D., and colleagues suggest that it may be possible to use previously fertilized egg cells to produce disease specific stem cell lines using somatic cell nuclear transfer, also called therapeutic cloning. This gives hope for new therapeutic approaches for amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease).

Prior efforts at nuclear reprogramming have relied on eggs which have proven difficult to obtain.

The new method indicates it may be possible to use cells left over from in vitro fertilization to generate stem cells that carry the genes responsible for disease such as ALS. In fact, the researchers have found that it may be possible to use fertilized eggs that would routinely be discarded in the course of in vitro fertilization efforts because they carry too many chromosomes to develop normally. 

“Our results provide several previously unexplored and technically feasible avenues toward the production of ‘genetically tailored’ human ES cell lines that are not constrained by the limitations of oocyte donation for research,” the investigators wrote in their report.

Eggan and colleagues found that, in mice and perhaps in humans - the cellular mechanisms required for genetic reprogramming are still present even after an egg is joined with a sperm. The chromosomes of newly fertilized mouse eggs can be removed and replaced with chromosomes from either a mouse embryonic stem cell or a skin cell from adult mice. In both cases, the reprogrammed cell went on to divide properly and could be used to produce embryonic stem cells lines. 

If this work can be replicated in humans, nuclei of adult skin cells could be placed into already fertilized eggs before they divide. The scientists could then produce stem cells that retain the ability to produce any type of cell. This suggests that with similar nuclear transfer from skin cells of ALS patients, embryonic stem cells might be produced for studying that disease.

Scientists believe that such embryonic stem cell lines might be useful in studying ALS because they will be able to generate large numbers of the motor neurons killed by ALS. The ability to produce large numbers of these motor neurons would be useful for drug discovery.

Read more about stem cells here.

Click here to read the PubMed article.