| Targeted Imaging and Targeted Therapy
A company has developed four products that target cancerous tumors and
unstable atherosclerotic plaque, the leading cause of heart attacks. Two of them
— targeted imaging products — detect tumors and unstable plaque and are
anticipated to go into clinical trials in 2005. The other two are targeted
therapeutics that take a drug treatment directly to the molecular marker
identified in the imaging step.
Reference: Gray, Sophia Oh (2004). “Kereos
uses molecular imaging to find tumors.” St. Louis Business Journal, April
23.
DNA Computer
Israel’s Weizmann Institute researchers have now programmed their biomolecular
computer to detect and treat prostate cancer and a form of lung cancer. It
can diagnose the disease and then produce a drug for it in a test tube.
Here’s roughly how it works: The computer is an enzyme solution containing
double-stranded DNA with single-stranded ends. The loose ends will automatically
bind to specific strands of target DNA or RNA “input” into the solution. If
binding occurs (i.e., if the disease is present) the enzyme cuts the DNA a
certain distance away, exposing new “sticky” ends, and the process repeats until
the enzyme eventually “outputs” the piece of DNA that acts as the drug.
“In one example,” writes Andrew Pollack in the New York Times, “the
computer determined that two particular genes were active and two others
inactive, and therefore made the diagnosis of prostate cancer. A piece of DNA,
designed to act as a drug by interfering with the action of a different gene,
was then automatically released from the end of the computer.”
A drop of water could hold a trillion of these devices, and indeed the intent
is that trillions would be administered intravenously to patients to detect
disease markers autonomously and independently as they travel around the body,
though it might take “decades” to get to that point. “It could work for any
illness for which there is a particular pattern of over-expression or
under-expression of genes which is characteristic for the disease,” the lead
researcher told Reuters’ Patricia Reaney.
Reference: Reaney, Patricia (2004). “DNA
Computer Detects, Treats Disease in Test Tube.” Reuters, April 28.
Reference: Pollack, Andrew (2004). “A Glimpse at the
Future of DNA: M.D.’s Inside the Body.” New York Times, April 29.
Targeted Therapy – Lung Cancer Success
In clinical trials, the cancer drug Tarceva “significantly” (no data
have yet been provided) improved survival for “certain” lung cancer patients who
failed to respond to standard chemotherapy. The drug is claimed to be the first
of its kind to show in a major study that the approach can extend survival in
patients in non-small-cell lung cancer. Tarceva is similar in many
respects to Iressa,* and the fifth cancer medicine with a proven survival
benefit, joining breast cancer drugs Herceptin and Xeloda, blood
cancer treatment Mabthera, and colorectal cancer drug Avastin.
Although Tarceva had failed to improve survival in patients already
undergoing chemotherapy, it did so in patients taking Tarceva alone after
chemo failed. Erbitux for colon cancer and Iressa also target EGFR
(epidermal growth factor receptors), but neither has demonstrated a survival
advantage in a clinical trial. Tarceva needs to show that it is as good
as Taxotere, which can add seven months to the lives of patients.
Alimta, a chemotherapy drug already approved for asbestos-related lung
cancer, extended the lives of patients with other forms of the disease by eight
months in a clinical trial, but has the usual side effects of chemotherapy.
* See “Beginnings of Pharmacogenomics” in this
section.
Reference: Unknown (2004). “Roche:
Our Cancer Drug Improves Survival.” Associated Press via Washington Post,
April 26.
Reference: Gellene, Denise (2004). “Genentech
Shares Leap on Drug News: The biotech’s stock rises 12% on data showing Tarceva
extends the lives of lung cancer patients.” Los Angeles Times, April 27.
Beginnings of Pharmacogenomics
The success of Iressa in shrinking lung cancer tumors in patients
carrying a recently identified specific genetic marker will have immediate and
dramatic impact, writes Raja Mishra in the Boston Globe. “Within months,
lung cancer patients worldwide could get the drug from the moment of diagnosis,
rather than having to first take the mostly ineffective and unpleasant
chemotherapy now prescribed. And those unlikely to benefit from it would be
spared the time and cost of taking the expensive new drug.” About ten percent of
lung cancer patients have the genetic marker, which translates to more than
10,000 patients a year in the US alone.
The other major benefit of Iressa is that it validates the
pharmacogenomic approach to treating disease, in which drugs are tailored not
just to the disease target but also to the patient’s individual genome, and is
spurring pharmacogenomic research and development.
Reference: Mishra, Raja (2004). “Drug
shows promise in lung cancer treatment.” Boston Globe, April 30.
Snatching Victory from Defeat in Drugs
After three patients taking Alimta during trials died suddenly in
1999, drug maker Eli Lilly halted the trial and turned the drug over to a doctor
and a mathematician. The team analyzed blood samples and medical records, found
the problem, and now Alimta is approved for mesothelioma, a rare type of
cancer caused by exposure to asbestos and may be approved for lung cancer. This
experience suggests there may be more gold in the 90 percent or so of
experimental drugs that fail. Other examples of clay transmuted into gold
include Viagra, now an impotence blockbuster, Evista, earning $1
billion-a-year to treat osteoporosis, and Strattera, for attention
deficit/hyperactivity disorder, all of which started out as failed drugs for
some other ailment.
The Alimta team discovered that patients with the most severe side
effects were those with low folic acid in their blood. The solution then was
simple: supplement Alimta with folic acid pills. It worked. In subsequent
tests of Alimta for non-small-cell lung cancer, it was found to lengthen
survival as much as Taxotere but with significantly less toxicity.
Reference: Burton, Thomas M. (2004). “By Learning
From Failures, Lilly Keeps Drug Pipeline Full.” Wall Street Journal, April
21.
ADAS Stem Cell Therapy Advance
Adipose-derived adult stromal (ADAS) cells purified from a rodent’s belly fat
have been used to heal large skull fractures in mice. ADAS cells have been
previously transformed into bone, cartilage, and neurons only in test tubes, but
this is the first time the transformation has been achieved in an animal. If it
can be successfully applied to humans, it means it could remove the need for
tens of thousands of bone grafts and prosthetic surgeries per year.
In 12 weeks, the ADAS cells filled between 70 to 90 percent of
four-millimeter fractures, compared to random natural bone formation in less
than ten percent of fractures in an untreated control group. With minimal
preparation, the ADAS cells began manufacturing bone as soon as they were placed
on a biodegradable polymer scaffolding containing apatite, a compound found in
natural bone.
They work as well as bone marrow stromal cells (which are already being used
in clinical trials of bone growth treatments), grow seven times faster (at least
in the lab), are easier to harvest from an individual’s fat (through
liposuction), and are more plentiful.
Reference: Cohen, Philip (2004). “Fat stem cells
heal broken skulls.” New Scientist, April 13.
Alzheimer’s Drugs a Bust?
At a meeting in late March at Johns Hopkins University, Alzheimer’s
researchers gave varying accounts of the effectiveness of current drugs used to
treat the disease. One said that most of his patients tried the leading drug,
but “only” ten percent of them found it worth continuing. Another said family
members often tell him that patients improve with the medicines or at least seem
to decline less steeply, and 7-10 percent had a noticeable, if temporary,
improvement. “The moderator,” reports Denise Grady in the New York Times,
told the doctors in the audience: ‘For us to tell you what to do, I think would
be wrong. All you can do is look at your soul and do the best you can.'”
Several researchers expressed anger about a study published last July in the
Journal of the American Geriatrics Society claiming that Pfizer’s
Aricept could delay a patient’s need for nursing-home care by nearly two
years. Apparently, Pfizer paid for the study and its scientists were among the
article’s authors. One thing is evident: Credible evidence-based medicine has
yet to reach this particular branch of medicine.
One expert declared that no breakthrough was near, and there would be no
“realistic reduction in the huge number of cases for decades.” Gina Kolata, also
writing in the New York Times, describes the same progress through more
optimistic glasses. “Things are more hopeful than perhaps people think,” and “We
are on the cusp of having something really useful,” one expert told her. The
optimism is vested in part in findings of possible links between Alzheimer’s and
cholesterol and/or high blood pressure, implying that statins or blood pressure
medications might hold an answer. Anti-inflammatory drugs have also been found
to lower the incidence of Alzheimer’s.
Reference: Grady, Denise (2004). “Nominal Benefits
Seen in Drugs for Alzheimer’s.” New York Times, April 7.
Reference: Kolata, Gina (2004). “A Glimmer of Hope
for Fading Minds.” New York Times, April 13.
Brain Scanning for Autism
A six-year-old autistic boy played a video game while a functional MRI (fMRI)
scanner measured his brain’s responses to light and motion, in experiments at
Georgetown and Children’s National Medical Center. fMRI tracks changes in blood
flow to help pinpoint sensory problems, motor control, and problems with
planning and reasoning.
The research is just part of a major coordinated effort across the United
States to further understand the disease.
Reference: Neergaard, Lauran (2004). “Advanced Scanning
Being Used for Autism.” Associated Press, April 12.
Breaking the Cell Barrier
A Canadian company has developed a “super-antibody” that binds to and blocks
an enzyme inside cells that triggers cell suicide. When further
developed, it could block cell death in people who have just had heart attacks
or strokes, but its significance extends much further. Because they can pass
through the cell membrane, super-antibodies could be developed to target
bacteria, viruses (including HIV), and cancer-causing abnormal proteins inside
cells.
Over a dozen antibody-based treatments are already being used to treat
diseases in people, but they all bind to molecules on the surface of cells or
viruses. Some can gain entry to a cell by being engulfed after binding to a
surface protein, but none can enter cells freely and target molecules inside
them. The new super-antibody is attached to a naturally-occurring protein
segment called a membrane-translocating sequence (MTS), enabling it to enter
(and exit) cells easily.
The company believes its super-antibodies could last in the body for up to a
month, entering and leaving cells until they find their target, where they would
then accumulate. The success of cell-penetrating super-antibodies may depend on
the concentrations they reach inside cells.
Reference: Coghlan, Andy (2004). “Super-antibodies
break the cell barrier.” New Scientist, April 19.
Living Bandage
Myskin is a new bandage made from a patient’s own skin cells, usually
taken by biopsy from the thigh. The cells are then cultured on a round plastic
patch. When the patch is applied over a wound, the skin cells release into the
wound and begin to grow new layers of skin.
The bandages have a longer shelf life than skin layers cultured without a
substrate and are much easier to apply. It is also beneficial in conjunction
with standard skin grafts, where the grafted skin often has holes that can be
patched using the Myskin bandage.
The treatment could have major implications for burn, amputation, and
diabetic ulcer patients, among others. A burns and plastic surgeon at a British
hospital said: “The bandages have produced some excellent results. We have only
used them in a few cases so far but they seem to work very well indeed.”
Reference: Womersley, Tara (2004). “‘Living bandage’ brings
revolutionary treatment.” The Scotsman, April 27.
Mind Control
The US Food and Drug Administration has approved a 12-month clinical trial of
Cyberkinetics’ BrainGate neural chip implant in the brains of five
paralyzed people. The chips transmit the patient’s thoughts in the form of
neural impulses to a computer, which analyzes and interprets them. The goal is
to enable the patients to operate a computer — and through the computer, other
electronic and robotic devices and prosthetics — by thought alone.
Cyberkinetics thinks its system could enable patients to type as fast as 20 to
30 words a minute.
The technique has worked in previous trials involving humans, as well as
monkeys. Cyberkinetics hopes to have a product on the market by 2007 or 2008.
The earlier trials in humans used only two electrodes per patient, whereas
the BrainGate has 100 electrodes, providing more information. The 2mm
chips will be implanted on the surface of the brain at the motor cortex, through
a small hole cut in the skull just above the ear. The electrodes penetrate to a
depth of 1 mm.
Reference: Pollack, Andrew (2004). “With Tiny Brain
Implants, Just Thinking May Make It So.” New York Times, April 13.
Mouse with Human Immune System
Swiss researchers have created mice with human immune systems, including
T-lymphocytes, B-lymphocytes, and dendritic cells that produce regular immune
responses. An enthusiastic American researcher said it could mean that
“effective vaccines for a whole range of pathogens, particularly those for which
no animal model exists, might be developed in record time,” and called it “a
giant step forward for vaccine development.”
Reference: Reinberg, Steven (2004). “Scientists Create Mice With
Human Immune Systems: Finding could lead to research for new treatments for
viral infections such as HIV.” HealthDay, April 1.
No Needles
A new technique called microscission delivers drugs through the skin using a
stream of gas containing crystals of aluminum oxide to remove the outer layer of
skin and create tiny holes or “microconduits” through which a drug can pass. In
tests on volunteers, the anesthetic lidocaine applied to the treated skin took
effect within two minutes. The technique could one day replace injections as the
standard method of delivering insulin to diabetics.
Reference: Graham, Sarah (2004). “New
Drug Delivery Technique Avoids Needles.” Scientific American, April 19.
Obesity Pill
French pharmaceutical company Sanofi is getting positive results with
Rimonabant, a drug that suppresses appetite and may have cardiac and
smoking-cessation benefits as well. The FDA-approved Xenical and
Meridia weight-loss drugs work modestly at best and have unpleasant side
effects. Another, Redux, was more potent but withdrawn from the market
after being linked to a deadly heart condition in some patients.
Preliminary data from four large studies show that Rimonabant reduces
weight significantly, by blocking receptors of a substance called cannabinoid 1,
which stimulates hunger and other cravings in the brain and is also present in
fat tissue. Sanofi hopes to file an application to the FDA in early 2005, and if
approved the drug could be on the market as early as 2006.
One other weight-loss drug, Axokine — an expensive biotech product
requiring injection — is in Phase III testing, but patients seem to develop
resistance to it over time.
Rimonabant is not without side effects, causing nausea, anxiety, and
diarrhea in some trial patients.
Reference: Tsao, Amy (2004). “Has
Obesity Met Its Match?” Business Week, April 8.
Regrowing Limbs
A new US Defense Advanced Research Projects Agency (DARPA) project called
ReGenesis will investigate the potential of limb regeneration in humans.
A senior DARPA official asked that since humans can regenerate a normal liver
after losing as much as 90 percent of it during surgery, “why can’t this
regenerative capability be available for human limbs or the brain and spinal
cord?”
The science of regeneration received a boost from the creation of Dolly the
sheep through cloning, and from the discovery of stem cells, but the genetic
mechanism of regeneration is still not fully understood. There is considerable
skepticism that it could ever work, and rightly so. Why, next thing you know,
they’ll be teaching Darwin in the schools.
Reference: Dalton, Alastair (2004). “Military scientists to
study regrowth of limbs.” The Scotsman, April 12.
Robot Therapy in Japan
“Robot therapy” is busting out all over in Japanese hospitals and nursing
homes. Initially, the robots provide simple companionship; ultimately, they will
provide physical care. One such robot is Paro, a furry baby seal
specifically designed for therapy and getting rave reviews following nursing
home trials in Japan, the US, and Europe. A commercial model should be available
this year for about US$2,800. Sony’s Aibo robo-puppy has improved
talking, watching, and touching activity in dementia patients at one Japanese
hospital.
Japan Times reporter Yuri Kageyama describes how “During a recent
session in Hachioji, a 1-year-old boy who has never left the hospital after
being born with a lung problem looked pleased playing with the robots — mostly
Aibo dogs that cocked their heads, chased a ball and made electronic
purring noises. The boy tried to stand.”
It seems increasingly clear that hospitals and nursing homes that do not have
real or robotic pets available to their patients are not providing the best
care.
Reference: Kageyama, Yuri (2004). “Robots
offer devotion, no strings attached: Machines take center stage amid dearth of
human contact for sick, elderly.” Japan Times: April 23.
Robot-assisted Physical Therapy
A 50-year-old man paralyzed from the neck down in a motorcycle accident is
learning to walk again with the help of a robotic exoskeleton called
Lokomat at the University of Texas Southwestern Medical Center. The
patient’s legs and hips are strapped into the exoskeleton, which simulates a
fluid walking motion on the treadmill over which the patient is suspended in a
harness. A computer measures movements and plots them on a graph.
“Our observations,” said a researcher, “support the theory that locomotor
training on the treadmill is driving reorganization in the spinal cord and
brain.” Essentially, the machine is teaching the spinal chord how to walk but
without the burden of weight — which is also a great benefit in reducing
fatigue in both the patient and the therapist.
After one month using the machine, the patient called it “a night and day
difference. I could walk for hours, if they’d let me.”
Reference: Unknown (2004). “Robotic technology
teaches spinal cord injury patients to walk again.” Medical News Today,
April 29.
Virgin Birth and Stem Cell Therapy
Japanese scientists have caused the quasi parthenogenesis — virgin birth —
of a mouse. No sperm or male cell was involved. It apparently does not mean that
lesbian couples can produce their own biological child, at least not with the
process used with the mouse, which was extremely inefficient, highly risky, and
required a very large number of eggs. As if that weren’t deterrent enough, under
legislation recently recommended by the Bush Council on Bioethics, the
parthenogenic approach would be outlawed for human reproductive purposes in the
US since it does not involve the union of sperm and egg. (See “Cloning Debate”
in the Policy section.)
Kaguya, as the baby mouse was named, was created by combining the genetic
material of two egg cells, the nucleus of one of which was to make it more
male-like by producing IGF-2, a protein crucial to embryo growth but normally
only produced by sperm-derived DNA. This was achieved by genetically altering
female mice so their eggs would produce IGF-2. The nucleus of one of these eggs
was then transferred into a regular egg that now contained the genomes of two
females, and which proceeded to divide and resulted in Kaguya. Kaguya and one
sister were the only live animals resulting from 457 reconstructed eggs.
Parthenogenesis is one method of obtaining human embryonic stem cells for
therapy, since parthenogenesis can easily be induced in human cells — but they
survive only just long enough to start producing stem cells. Apparently, the
Bush constraints on federally-funded stem cell research also prohibit the use of
stem cells obtained this way because it considers even a parthenote to be an
embryo. Creating parthenotes is much easier and one would think would be less
controversial than the other way of obtaining ESS — creating cloned real,
viable embryos.
Reference: Westphal, Sylvia Pag�n (2004). “‘Virgin birth’
mammal rewrites rules of biology.” New Scientist, April 21.
Reference: Philipkoski, Kristen (2004). “Fatherless Mice
Muddy the Water.” Wired News, April 27. |
