From: Jeff Davis (jdavis@socketscience.com)
Date: Sun Sep 12 1999 - 10:57:11 MDT
Friends,
The following was posted to the cryonet:
Message #12402
From: "Robert Moore" <robertmoore@hotmail.com>
Subject: An important medical breakthough!
Date: Sat, 11 Sep 1999 17:54:23 PDT
The article below heralds a very important medical breakthough. It
will probably lead to complete cures of such diseases as sickle cell anemia
and hemophilia. The defective cell DNA is repaired, permenantly! I expect
that this technique could also possibly be used to eliminate genetic
predispositions to certain cancers.
A MORE IMPORTANT QUESTION: (What do the anti-aging experts on Cyronet
think?) Could this (chimeraplasty) or a derivative technique be used to
stop genetically "programmed" aging processes???
======================================================================
Gene repair in rats raises hope for genetic diseases
NEW YORK (Reuters Health) -- Through the use of a novel technique termed
'chimeraplasty,' researchers have, for the first time, successfully repaired
the genetic defect associated with Crigler-Najjar syndrome, a rare but
devastating liver disease, in lab rats.
The finding may lead to gene therapies that cure other genetic diseases such
as hemophilia and sickle cell anemia, according to the report published in
the Proceedings of the National Academy of Sciences.
Principal investigator Dr. Clifford Steer, of the University of Minnesota
School of Medicine in Minneapolis described his team's work in an interview
with Reuters Health. "We did two things that were important: one, we
developed a system whereby we could go in and literally rewrite the genetic
sequence in a specific gene of interest; and two, we developed a technology
that would do it in the hepatocyte, the type of liver cell that controls the
major defect (of Crigler-Najjar syndrome)." The syndrome is characterized by
an innability to properly metabolize bilirubin, a byproduct of normal red
blood cell degradation. The genetic disease features jaundice and
destructive changes in parts of the brain.
The researchers created a molecule called a chimeraplast, which is based on
the structure of the defective gene and "targeted to that portion of the
gene with the mutation," Steer explained. When the molecule is introduced
into the cell, "it tricks the cell into thinking that there is a defect in
its DNA sequence for that particular gene and by tricking the cell, the cell
basically repairs (what it perceives as) its own defect."
What is being accomplished, in essence, is genetic repair without having to
employ techniques that require "the introduction of new genes (via
genetically modified viruses) to take the place of the (original
defective)genes," as is the case in conventional gene therapy, according to
Steer.
"All we are doing is repairing the genetic defect in a gene that is already
there," he explained. "And when you think about it, what is really the best
way to do gene therapy? It would be to go in to correct the defect so that
the gene is in the right position, controlled and regulated by the
(appropriate) regulatory elements that would normally control that gene."
An important aspect of this technology is that "once the genetic change is
made, the repair is permanent," Steer said. And although this work was
carried out in an animal model, the Gunn rat -- which has a genetic defect
similar, though not identical, to that seen in human Crigler-Najjar syndrome
-- Steer "feels very confident that it's going to work in humans. It works
in animal models, it works in plants, in works in bacteria, it works in any
structure that has DNA in it."
The type of mutation corrected in the study involves an omission or deletion
of one "letter" in a specific DNA genetic sequence. DNA is composed of basic
units called nucleotides, which are designated by specific letters. These
combine into sequences that "spell out" a genetic code. Changing one
"letter" into another is easier than replacing a missing letter, Steer said,
and in the human disease, changing rather than replacement is required to
correct the defect. Consequently, "we hope that our results will be even
more exciting in human beings than they were in the rodent model."
Together with his colleagues at the Albert Einstein College of Medicine in
the Bronx, New York, Steer expects to submit a clinical trial application
for the technique to the Food and Drug administration early next year.
"We're going to involve 3 to 5 pediatric patients already identified with
Crigler-Najjar, who live in the Amish country in Pennsylvania," Steer told
Reuters Health. He commented that the Amish have a very high frequency of
this disorder and that these particular children all have the same genetic
defect, a mutation at a single point in the genetic code.
The majority of genetic diseases in human beings are single-point mutations,
Steer explained, "so we have a technology here that can be applied to many
different types of disease. The technology is here, it's here to stay, and
it is very different from gene therapy."
The investigators are already developing a number of other animal models to
look at potential clinical applications in disease such as Gaucher's
disease, hemophilia, thalessemia, and sickle cell anemia. Though sickle cell
anemia's defect originates in the bone marrow, Steer believes that the team
will be able "to develop a delivery system for the chimeraplasts" that will
direct them to the marrow, the site of the stem cells from which the
defective red blood cells in sickle disease originate.
"It's going to be more challenging than liver, only because it's bone marrow
and the progenitor cells are more difficult to deal with," he noted.
Steer emphasized that though the results achieved thus far are "very, very
exciting," with potentially "broad-based application," much remains to be
done. Further developing and refining the technology's seemingly limitless
possibilities will "keep the medical profession busy for many, many years,"
he predicts.
Source: Proceedings of the National Academy of Sciences USA
1999;96:10349-10354.
Best, Jeff Davis
"Everything's hard till you know how to do it."
Ray Charles
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