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Promising research - a question.

Stephan D. Bouman S.D.Bouman at biol.rug.nl
Fri Feb 16 13:55:21 EST 1996

On Thu, 15 Feb 1996 12:52:26 GMT, sberman at netcom.com (Stanley Berman)

>What would you say are the top 3 to 5 most promising lines of research 
>in neuroscience in terms of their potential to contribute to disease 
>prevention or treatment in the future?
>These research opportunities might be fundamental/basic research topics 
>or more applied areas of research.

I don't know that much promising lines of research, but the one that
immediately comes to my mind is antisense.
I think that research about the so-called "gene therapies", and
especially the antisense technique, is very promising. These
techniques inhibit the synthesis of proteins by inactivating the DNA
or mRNA involved in this synthesis. Because this is based on the
sequence of the nucleic acid, the inhibiting can be highly specific.

There is a lot of research on this techniques in the fields of
anti-cancer drug design and anti-virus drug design (and of course
especially concerning the HIV virus). As soon as you know the
base-sequence of the viral RNA, you can design an antisense probe
against it, which will disable/inhibit replication of the RNA and thus
also inhibit development of the disease. Same for cancer: when you
know the sequence of the DNA of the cancer-causing protein, it can be
inhibited by antisense.

The antisense technique still has some problems. Because antisense
itself is a (synthetic) nucleic acid, it is unstable and it is rapidly
degraded by nucleases. It can also be toxic. A lot of research is now
focused on developing modifications of the antisense nucleic acid;
modifications that improve stability and transport into the cell and
that decrease toxicity.

Antisense is not well-known yet in the field of neuroscience, but that
is changing rapidly, since antisense can be a very powerful tool in
examining the effects of certain proteins (neurotransmitters, enzymes,
receptors, etc.). I used it in my own research to inhibit hippocampal
glucocorticoid receptors.

Good review articles for the use of antisense in (neuro)science are:
Cohen, J.S. and M.E. Hogan; The New Genetic Medicines. Scientific
  American (1994 Dec) 50-55
Pilowsky, P.M., S. Suzuki and J.B. Minson; Antisense oligonucleotides:
  a new tool in neuroscience. Clinical and Experimental Pharmacology
  and Physiology (1994) 21: 935-944

>Are there any of these topics where there would be a consensus or broad 
>agreement in the neuroscience community?

I am not sure about consensus about antisense, but I *think* most
scientists will agree that antisense can be an interesting new
treatment of certain diseases and a useful tool for neuroscientific

Maybe we should request everybody on this group to give their comments
on antisense...



s.d.bouman at biol.rug.nl

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