| RNAi Is Taking Off
RNA interference (RNAi) was discovered in 1998 as a natural process in which
RNA molecules interfere with the expression of particular genes. The
mind-boggling implication was that RNAi could, in theory, be used to block the
expression of any identified disease gene.
Alnylam Pharmaceuticals, founded in 2002 by some of the early RNAi
researchers, including a Nobel laureate, is working to synthesize small RNA
molecules for RNAi drugs. It is focusing first on cancer and diabetes, and hopes
to have a drug in clinical trials as early as the end of 2005. The company
raised $43 million in venture capital in its first year, and recently announced
a partnership with Merck to develop RNAi drugs.
But delivering on the promise won’t be easy. First, RNA molecules soon
degrade in the body, so a way must be found to keep them intact for long enough
to do their job. And second, there is competition. Sirna Therapeutics expects to
begin clinical trials of an RNAi drug for hepatitis B and C and macular
degeneration late next year, and will patent a way to stabilize the fragile RNA
molecules. Other RNAi companies are variously targeting hepatitis B and C, HIV,
leukemia, macular degeneration, and diabetic retinopathy.
Reference: Lok, Corie (2003). “The RNA Cure?
Alnylam Pharmaceuticals is poised to commercialize drugs made from RNA
molecules.” Technology Review, November.
Impending Cure for Deafness
Scientists have succeeded in growing inner-ear hair cells from mouse
embryonic stem cells. The achievement could eventually lead to cures for
permanent deafness and tinnitus. The researchers used growth factors to coax the
stem cells into becoming precursor inner-ear hair cells, which were then
inserted into the developing ears of chicken embryos. The cells integrated into
the inner ear and produced genes and proteins specific to adult hair cells. They
also generated bundles of hairs. The feat is more than a significant advance in
treating deafness; it is further evidence of the potential of stem cell therapy.
Reference: Howarth, Angus (2003). “Deafness cure is
nearer.” The Scotsman, October 28.
Doubts About Adult Stem Cell Therapies
UCSF researchers took cells from the bone marrow of adult mice and
transplanted them into other mice, where they migrated through the blood into
different organs and fused with brain, heart, and liver cells. The finding is
evidence that bone marrow-derived cells do not, as some think, differentiate
into specialized cells themselves, and the UCSF researchers are urging
postponement of planned clinical trials that would test the differentiation
hypothesis in human patients.
But cell fusion is clearly worthy of further study, they say, since whether
or not it plays a role in cell repair, it might still have a therapeutic role.
Although they detected no evidence of cell fusion in skeletal muscle, gut,
kidney, or lung, the possibility that such could be obtained under different
experimental conditions cannot be ruled out.
Reference: UCSF (2003). “UCSF-led
study raises doubts about marrow cell treatment for brain, heart.” Press
release, October 14.
New Stem Cell Lines
In efforts to find a cure for his own diabetic children, a Harvard professor
has created 17 new stem cell lines from embryos discarded from fertility
clinics. He has announced he will make the new lines freely available to
researchers early in 2004. President Bush’s restrictions limiting federally
funded work on stem cells to a small number of cell lines created prior to April
2001 have substantially hampered stem call therapy research.
The professor says the so-called “presidential” stem cell lines are too few,
getting too old, and cost too much. He hopes that stem cells can be coaxed into
becoming insulin-producing cells that can be grafted into diabetics, such as his
children, for a permanent cure. Other stem cell researchers have welcomed his
“open source” contribution of the new lines.
Reference: Associated Press (2003). “New Stem Cell
Lines Developed.” Wired News, October 30.
Gene Repair
A new approach to gene therapy appears to be able to repair the devastation
wrought by diseases such as polycystic kidney disease. Instead of just injecting
healthy genes to replace defective ones wholesale, as it were, a gene has been
engineered to repair the malfunctioning cells by replacing defective portions of
mRNA molecules with the correct sequences. In (presumably in-vitro) tests, cells
carrying a mutated gene that causes a muscle-wasting disease stopped producing
the harmful protein and began producing the normal one. Testing on animals could
begin within two years.
Reference: Unknown (2003). “Buckyball
Antibiotics.” Prototype, October.
Grow Your Own Organs II
A cardiologist with an interest in newts’ ability to regrow an eye or leg or
even reconnect a severed spinal cord believes they may hold the key to human
healing. He is not the first to want to investigate how to apply newt
regenerative biology to humans, but he is among the first to have technology to
understand the biology at the genetic level.
Just a small enhancement to human regenerative abilities would have profound
therapeutic effects: “Patients with kidney failure need just 10 percent of their
cells back and they can go off dialysis,” one of the cardiologist’s colleagues
told Wired‘s Jennifer Kahn. “Likewise, when you have a heart attack,
there’s a big difference between losing 20 percent of your heart cells and 40
percent.” The cardiologist and others have formed a company to research and
develop regenerative therapies for these organs as well as for the pancreas,
skin, central nervous system, veins, joints, and eyes.
It appears that we may have strong regenerative abilities as fetuses, if we
are anything like sheep, whose fetuses have been found to recover from a deep
cut seamlessly in the first two trimesters, but be scarred for life if the cut
occurs later than that. It appears there is a genetic switch that gets turned
off, and the question they seek to answer is can it be turned back on? Part of
the answer came unexpectedly in late 1998, when — against their wildest
expectations — they succeeded in “de-differentiating” mouse muscle cells back
into stem cells by treating them with a liquefied extract made from a newt’s
regenerating leg cap. Later, they caused stem cells de-differentiated in this
manner to re-differentiate into muscle, bone, or fat cells by applying growth
factors.
In short, they had essentially shown that regeneration in mammals was
possible. The discovery could also be a major breakthrough for stem cell therapy
research, since a limitless supply of fresh stem cells could be obtained by
de-differentiating adult cells.
The researchers now think that a quick human self-repair kit could be as
simple as a key protein applied to the damaged area of the body, to “start a
cascade of genetic instructions, which in turn would prompt a cell to
dedifferentiate.” Taken after a heart attack, for instance, the protein could
slow the scarring process while boosting the production of healthy
cardiomyocites.
The challenge of this work appears breathtaking, but given the breathtaking
new tools and knowledge at our disposal today — with much more to follow
tomorrow — it would seem almost irresponsible not to be bold.
Reference: Kahn, Jennifer (2003). “Regrow Your
Own Broken heart? No problem. New liver? Coming right up. The road to
regeneration starts here.” Wired, Issue 11.11, November. |
