Experimental antibiotic compounds could prevent bacterial
reproduction without damaging human cells; while existing antibiotics may be
made more potent by attaching Buckyballs to their
molecules.

Our new molecular tools are extracting from Nature several potent drugs that
may eliminate pain existing drugs cannot touch,
including one that can stop pain long before it starts.
And extra potency is being wrung out of existing drugs, by
using them in combination with new ones or to treat different
diseases.

The U.S. National Cancer Institute has committed more than a million dollars
to help a researcher prepare the experimental drug HB22.7a for clinical trials
in lymphoma and leukemia patients. The drug is a monoclonal antibody that
targets proteins in cancer cells and induces the cells to self-destruct.

It targets B lymphocytes, the cancerous cells of leukemia and lymphoma. The
drug’s developer claims says it improves upon Rituxan, approved by the
U.S. Food and Drug Administration in 1997 and successfully used to shrink some
lymphoma tumors by stimulating the patient’s immune system to combat the cancer
cells.

HB22.7a also has potential for treating rheumatoid arthritis and
other autoimmune diseases, and could be ready for human clinical trials in one
to two years.Reference: Griffith, Dorsey (2003). “UCD
doctor studies new cancer drug.” Sacramento Bee, October 8.

Breast Cancer Preventive Drug in Trials

A 6,000-patient international trial of anastrozole, an experimental
breast cancer preventative drug, began last month in the United Kingdom. The
drug could reduce the risk of breast cancer by more than 50 percent in women at
elevated risk, compared to tamoxifen, which reduces it by about a third.
Anastrozole is also predicted to have much lower risk of side effects,
which include endometrial cancer in the case of tamoxifen.

Early data from a 9,000-patient clinical trial comparing the use of
tamoxifen versus anastrozole for treating breast cancer in 9000
postmenopausal women from 21 countries suggest that tamoxifen and
anastrozole reduce the incidence of tumors in the opposite breast of
women who already had cancer, by about 40 and 70 percent respectively.

Tamoxifen stops the action of estrogen on cells in the breast, while
anastrozole inhibits the aromatase enzyme used to make estrogen.

Reference: Bhattacharya, Shaoni (2003). “Major trial
tackles breast cancer prevention.” New Scientist, September 30.

Tarceva Down But Not Out

In Phase III clinical studies, the “smart bomb” cancer drug Tarceva
failed to achieve its primary goal of improving overall lung cancer survival
rates when given in combination with standard chemotherapy. Tarceva is an
epidermal growth factor inhibitor similar to rival Iressa, which also
failed as a front-line therapy when combined with chemotherapy in tests last
year.

The disappointing results do not mean Tarceva is dead. It is now being
looked at as a potential third-line, single-agent treatment for lung cancer
patients who have failed to benefit from conventional chemotherapy, and as a
treatment for brain and pancreatic cancer. Iressa was already approved in
May by the U.S. Food and Drug Administration for last-resort treatment of
advanced non-small cell lung cancer patients.

Data from second- and third-line non-small-cell lung cancer trials are
expected in early 2004.

Reference: Emery, Chelsea; and Ben Hirschler
(2003). “Roche,
Genentech, OSI Cancer Drug Fails.” Reuters/Yahoo, October 1.

See also “Promising Lung
Cancer Drug” in the August 2003 issue of Health Futures Digest.

New Antibiotic

U.S. researchers have developed a new class of antibiotic compounds, known by
the experimental name CBR703, that could sidestep the growing problem of
bacterial resistance to antibiotics by preventing bacteria from reproducing.
Like standard antibiotics, they work by inhibiting the RNA polymerase enzyme
necessary for gene expression, but do so “in a unique way,” writes a Reuters
reporter. It seems the researchers found “something that inhibited bacterial RNA
polymerase” which in turn led them to figure out the structure of the enzyme and
“determine how to improve the inhibitors further to make them more effective.”

CBR703 was successfully tested on E. coli, but did not “affect human cells in
the same way.” We take that to mean it killed the E. coli, but it did not kill
human cells, though it is unclear whether the human cells were otherwise
affected. If they were not, then the new compounds may have significant
potential.

Reference: Unknown (2003). “New Antibiotic
Kills Tough Bugs.” Reuters, in Wired News, October 23.

Antibiotic Buckyballs

A Rice University chemist has fabricated an antibiotic-fullerene complex able
to target specific tissues.

In a lab experiment targeting the bacterial bone infections that afflict some
orthopedic surgery patients, two molecules of the antibiotic vancomycin
and a chemical that binds only to bone were attached to a fullerene molecule.
The engineered molecular complex precisely targets the infected tissue. Animal
testing could begin in 2004.

A similar complex using the antibiotic Cipro is being tested for
treating anthrax infections.

Reference: Unknown (2003). “Buckyball
Antibiotics.” Prototype, October.

New Cures from Old Drugs

Two recent articles show that existing drugs may actually benefit from the
introduction of newer drugs, either in combination with the newer drug or to
treat a different disease than originally intended. One article reports that
oral doses of CellCept, a drug used to prevent organ rejection in
transplant patients, works as well as chemotherapy for treating kidney failure
from lupus but with fewer side effects. Of 130 participants in a recently
completed FDA-sponsored study who received either CellCept or intravenous
doses of cyclophosphamide, the CellCept group produced 14 complete and 21
partial remissions compared to four complete and 14 partial remissions in the
chemotherapy group. Fifty-two of the 66 patients on CellCept completed
the six months of treatment, while only 38 of the 64 patients on chemotherapy
finished their treatment. Severe infections also were less common in the
patients taking CellCept.

The second article reports a small study in which the psoriasis drug
Amevive was found to be significantly more effective in treating
rheumatoid arthritis in combination with the old-line therapy of methotrexate,
compared to treating with methotrexate alone. The combination of billion-dollar
blockbuster Enbrel and methotrexate has also found to be markedly more
effective than methotrexate alone.

All of which is good news not only for lupus and arthritis sufferers, but
also for the makers of cyclophosphamide and methotrexate.

References: Schneider, Mike (2003). “Drug
Offers Help for People With Lupus.” Association Press/Washington Post,
October 24; Johannes, Laura (2003). “Biogen’s
Psoriasis Drug Helps Treat Arthritis, Report Finds.” Wall Street Journal,
October 25.

See also “New
Cures from Old Drugs” in the June issue of Health Futures Digest.
http://www.healthfuturesdigest.com/200306/p5.html#New_Cures_from_Old_Drugs

Painkillers

The venom from a killer snail has been turned into the painkiller drug
ziconotide, claimed to be “about a thousand times more potent than
morphine.” The drug is not yet approved by the U.S. Food and Drug Administration
and can cause severe side effects. But it is at the forefront of a new
generation of drugs that block the electrical impulses that generate pain
signals, using our relatively new ability to synthesize molecules more potent
yet safer than those in nature. Human trials of some of the drugs could begin
within the year.

Morphine and its derivative OxyContin act throughout the nervous
system, not just on pain-sensing nerves, causing side effects. Cox-2 inhibitors
for arthritis pain (Vioxx, Celebrex) are more targeted but less
potent. The new pain drugs target ion channels, which play a key role in
generating or transmitting pain signals and about whose chemistry there has been
an explosion of new knowledge, including several recently discovered ion
channels that seem to be found exclusively on the specialized nerve fibers that
sense pain. Drugmakers are racing to produce drugs to block these channels and
relieve pain from osteoarthritis and the often untreatable neuropathic pain
caused by diabetes, cancer, AIDS, kidney disease, chronic infections, and even
some prescription drugs.

There remains much work to do and many basic questions to be answered, but
human trials on several new painkillers are slated for as early as late 2003,
and the exponentially accelerating explosion of technologies for understanding
biological processes at the molecular level will continue to provide answers and
drive rapid progress.

Reference: Gerber, Ken (2003). “Stopping
Pain.” Technology Review, November.

Military Medicine in Double Quick Time

A U.S. Defense Advanced Research Projects Agency (DARPA) project called
“Persistence in Combat” is developing technologies to automatically control
acute pain and blood loss in an injured soldier within five minutes, so the
soldier can quickly rejoin the battle. The technologies include a sensor that
scans the eye for internal trauma, a bandage that stimulates skin repair with
electrical impulses, and — perhaps most interesting — a “pain vaccine” known
as RI624 to be tested in humans in 2004. The drug uses an antibody that blocks a
neuropeptide pain transmitter. Unlike morphine, RI624 does not interfere with
cognitive faculties, and can be taken days in advance of anticipated or
potential pain. (See “Painkillers” in this section for news of other advances in
this area.)

The imminence of human trials shows how “surprisingly close to reality” these
technologies are, notes Wired‘s Noah Shachtman.

Reference: Shachtman, Noah (2003). “Saving Pvt. Ryan
… From Pain.” Wired News, October 10.