[Ecommerce] Re: Critical Research and Bayh-Dole

[Seth Johnson]

And here's another example:

> http://www.depmed.ualberta.ca/dca/
> http://www.depmed.ualberta.ca/dca/media.asp

The following are two of the articles linked to from the above page.
But go to the above page.  They're looking for donations.

-- Seth


> http://www.depmed.ualberta.ca/dca/economist.pdf


Cancer biology

Cramping tumours


Jan 18th 2007


An old observation about cancer cells may lead to a new treatment


CANCER cells manage their energy production in a most peculiar way. A
healthy cell relies on its mitochondria
(descendants of bacteria that took up residence in the single-celled
ancestors of animals and plants about 2
billion years ago) to oxidise sugar molecules and release useful
energy. Most cancer cells, however, use a less
efficient mechanism called glycolysis to power themselves. They thus
cut their mitochondria out of the loop.

That cancer cells often rely on glycolysis was discovered by Otto
Warburg in 1930. But until recently the Warburg
effect, as it has come to be known, was little more than a
curiosity=97and a contentious one at that. Now, it looks
a lot more interesting, for Evangelos Michelakis and his colleagues at
the University of Alberta, in Canada, are
testing a drug called dichloroacetate that suppresses the Warburg
effect and reactivates the mitochondria. The
result shows why mitochondrial suppression is so important to tumours:
when they are unsuppressed, the
tumour they are in stops growing.

At first sight, this is all terribly paradoxical. Cancer cells
multiply rapidly=97and such multiplication requires a lot of
energy. Normally, glycolysis is merely the prelude to energy
production. It breaks glucose down into molecules
called pyruvate that are fed to the mitochondria for processing. This
breakdown yields some energy, but not
much. However, it does not require oxygen=97a substance that cancer
cells are frequently deprived of, as tumours
often fail to develop the blood vessels needed to supply it.

Cancer cells seem to adjust so well to glycolysis that even if blood
vessels do grow into a tumour and the oxygen
thus returns, they stick with it. From the cancer's point of view that
is a very good choice, as one of the other
jobs of the mitochondria is to kill a cell if it goes bad=97a process
known as apoptosis.

The role of dichloroacetate is to re-activate the mitochondria by
stimulating an enzyme that feeds pyruvate into
their energy-generating cycle. (The drug is already tested and
approved for the treatment of certain
mitochondrial diseases.) It seems this reactivation also allows the
mitochondria to stimulate apoptosis.

At least, that is what Dr Michelakis thinks is going on. His results
are certainly reminiscent of those obtained last
year by Valeria Fantin and Philip Leder of Harvard Medical School. Dr
Fantin and Dr Leder used a trick called RNA
interference to modify glycolysis in the tumours of some specially
bred laboratory mice.

If too much pyruvate is being made, the surplus is normally turned
into lactic acid. (Athletes whose muscles
demand more energy than their mitochondria can deliver suffer from a
build-up of lactic acid as their glycolytic
pathways go into overdrive. It is this build-up that causes cramp.)
The RNA interference employed by Dr Fantin
and Dr Leder stops the conversion of pyruvate into lactic acid,
causing it to build up. Their hope was that,
overwhelmed with pyruvate, the mitochondria would be forced to
respond.

And respond they did. Apoptosis shot up in the treated animals. Dr
Fantin and Dr Leder also observed a marked
decline in tumour growth rates. The survival rate of animals went up,
too. None of the members of an untreated
control group survived the four-month period over which the experiment
was conducted. By contrast, 80% of the
treated animals survived.

RNA interference is the subject of eager investigation among
pharmaceutical companies, but so far it has yet to
yield a drug approved by the regulators. Dichloroacetate, by contrast,
is already employed for other purposes.

That does not mean it will work as an anti-cancer agent in the real
world, of course. But it does give it a head
start. And even if dichloroacetate itself does not work, Dr
Michelakis's study points towards a new approach to
stopping cancer in its tracks.

---

> http://www.depmed.ualberta.ca/dca/2007-01-17_globe_article.pdf

Long-used drug shows new promise for cancer

Therapy prescribed for metabolic disorder now found to shrink tumours
in lab rats

Byline: Andre Picard
The Globe And Mail
Wednesday, January 17, 2007
Page: A17


ANDRE PICARD PUBLIC HEALTH REPORTER With reports from Avis Favaro and
Elizabeth St. Philip, CTV News

Imagine, if you will, a drug that shrinks cancer cells and can even
make tumours disappear. A couple of spoonfuls a day of powder in a
glass of water is all you need.

There are no nasty side effects like nausea and hair loss, and no
damage to internal organs such as with traditional chemotherapy. And
it costs only about $2 a dose.

Too good to be true?

Not according to a Canadian researcher who stumbled upon the
potentially new anti-cancer agent called dichloroacetate, or DCA, a
drug long used to treat rare metabolic disorders.

"This is one of the most exciting results I've ever had," said
Evangelos Michelakis, an associate professor of medicine at the
University of Alberta in Edmonton.

"But I can't be overenthusiastic until it works in a human being."

In a paper published in today's edition of the medical journal Cancer
Cell, Dr. Michelakis and a group of researchers from the U of A and
the University of Ottawa, report on how they were able to use DCA to
shrink human lung-, breast- and brain- cancer tumours in both lab rats
and in a test tube.

While this type of research in laboratory animals does not generally
generate a lot of enthusiasm, in this case the findings are creating a
stir because DCA has actually been used safely in humans for decades
-- in treating rare inherited metabolic disorders such as lactic
acidosis, not cancer.

"One of the big concerns about drugs is that they can harm people but
we already know this drug is safe. It doesn't even affect normal
cells," Dr. Michelakis said.

The research challenges one of the fundamental premises of cancer
biology, that mitochondria (the energy producing units of cells) are
permanently damaged by cancer.

What Dr. Michelakis and his team found is that while mitochondrial
function is suppressed, it can be revived with DCA, which makes the
cancer cells susceptible to dying. (Most cancers become resistant to
standard chemotherapy by suppressing mitochondrial function.)

In other words, the drug works by revving up the engines of normal
cells, allowing them to work normally and driving cancer cells to
commit suicide.

"This is the holy grail of cancer therapeutics -- how to kill the
cancer cells and spare normal cells," Dr. Michelakis said.

Dario Altieri, a professor in the department of cancer biology at the
University of Massachusetts Medical School in Worcester, Mass., said
the research is "exciting" and that DCA has a lot of potential.

Dr. Altieri said DCA needs to move quickly from the lab into human
testing. But he cautioned that there is a real possibility that will
not happen, largely for economic reasons.

There is no longer a patent on DCA, meaning it is not owned by any one
company. As a result, there is little chance of making a large profit,
even if the drug works remarkably well, and hence no incentive for
pharmaceutical companies to invest in research.

Dr. Michelakis acknowledged this is a real practical problem, but he
expressed hope that public funding bodies like the Canadian Institutes
for Health Research (which funded the lab study) will step in.

"Nobody is going to make a billion dollars from this drug," Dr.
Michelakis said. "But maybe it will help a lot of people with cancer."