Gorrillas in Our Midst - for members since 2005

[Guest guest]

(I finally found my article I wrote for CMT World Magazine on the existence of

the CMT 1A gene being 6-7 million years old). I'm doing some other writing on

the use of primates in research, and by

'accident' found this FYI)

Gorrillas in Our Midst (written in 2005 for CMT World Magazine)

by Gretchen Glick

Over a decade of research studies on chimpanzees and gorillas suggests that the

CMT 1A gene has been with our " family " for six to seven million years. Evolution

of primates to Homo Sapiens (man) thus indicates we are dealing with a powerful

genetic marker in CMT. And now, our species has acquired the ability to direct

it's own genetic destiny, for the first time during life on this planet.

Prior research presented by CMT World Magazine covered Pre-Implantation Genetic

Diagnosis, a type of in vitro fertilization, for procreation of CMT free

children. Now RNA gene therapy promises an even greater hope - to silence

defective CMT/HSMN genes and thus totally arrest the disorder, and other

inherited neuropathies, with the use of " microRNAs " .

RNA is short for Ribonucleic acid. Its main function is to copy genetic

information from DNA and then translate it into proteins. The RNA world

hypothesis explains that the universal ancestor to all life once relied on RNA

to carry information (like DNA does now) and to catalyze biochemical reactions

like an enzyme. This means that RNA was the dominant and most likely only form

of life before the emergence of the first cell.

In the late 1990s and into the first year of the new millennium, there was

increased evidence of more complex transcription occurring in mammal cells. This

pointed us to a world where a more widespread use of RNA will be used,

specifically in gene regulation.

A particular class of " microRNAs " now clearly plays an important role in

regulating genes across huge evolutionary time scales, and suggests microRNAs

could be involved in shaping the diversity of life, including the arrestment of

genetic disorders such as CMT and other inherited neuropathies.

Recent research from the Chinese Academy of Medical Sciences (2005) showed that

a close relationship exists between small RNAs and human disease, especially

neurological disorders and forms of cancer. This study proved microRNAs play an

important role in maintaining the stable state of chromosome structure and

regulating the expression of protein coding genes. Thus, gene therapy using

microRNAs is promising as a therapeutic agent for CMT/HMSN and other inherited

neuropathies.

Discovered only a few years ago, microRNAs are small, but powerful molecules

that now play a pivotal role in gene silencing, one of the body's main

strategies for regulating its genome. A mere 22 nucleotides in length,

microRNAs appear to work by binding to and somehow interfering with messenger

RNA, itself responsible for translating genes into proteins.

Researchers at The Wistar Institute have identified a two-protein complex,

called the " microprocessor complex " , which controls the earliest steps in the

creation of microRNAs in the cell nucleus. Of even greater importance is the

current identification of a three-protein complex that picks up the process in

the cell cytoplasm and carries it through to the maturation of the finished

microRNAs.

These two cutting-edge breakthroughs trace the generation of microRNAs from the

genes that give rise to long primary RNA molecules through to the mature

microRNAs that target messenger RNA. This research also shows that the finished

microRNAs are associated with a protein called Argonaute 2, known to be involved

in inactivating messenger RNA. This action then, would completely shut down

genes responsible for genetic disorders, meaning total arrestment for CMT/HMSN

and inherited neuropathies.

Ramin Shiekhattar, Ph.D., an associate professor at Wistar commented that " In

our research, we were able to link processing of the microRNAs directly through

to the molecules responsible for silencing genes. The microRNAs provide

specificity for those molecules, which do the actual work of gene silencing. "

But, before microRNA therapy can be used to silence CMT, researchers must

identify ALL genes responsible for ALL types of CMT. Because of the prevalence

of CMT 1A in humans (roughly 75%) microRNA gene therapy will most likely begin

with this type of CMT, followed by CMT X. It is unknown at this time exactly

WHEN this form of gene therapy will be available for persons with CMT.

Directing our own genetic destiny presents us with new questions and many new

answers, as we travel " back to the future " into a " brave new world " without

CMT/HMSN or other inherited neuropathies.

No part of this article may be used elsewhere without the written permission of

the author. Ms. Glick gratefully acknowledges the research of H. Kiyosawa,

P.Chance, P. Stankiewicz, SS Park, K. Inoue and JR Lupski, Jurgen Brosius, Evan

Eicher, the Medical Institute, the ItalianUniversity of Bari, the

Max Planack Institute of Evolutionary Anthropology, Washington School of

Medicine in St. Louis, The Chinese Academy of Medical Science and the Wistar

Institute. We will continue to report microRNA news as it is received.