| Cancer Vaccines Roundup
The first cancer vaccine could be in general use in three to five years,
writes Corie Lok in Innovation News. Globally, more than 50 vaccines are
currently being tested against melanoma and kidney, lung, breast, prostate, and
other cancers. Several are in phase III clinical trials, and at least two trials
should conclude within a year.
In some of the trials, a few cases have gone into remission (the most
desirable outcome), and the disease has slowed in a few others. Unknowns include
the risk of causing the immune system to destroy healthy cells as well as cancer
cells. Some vaccines require labor intensive pre-treatments that could be
prohibitively expensive. Not least, cancers could adapt to defeat the vaccines.
For these reasons, even proponents believe that cancer vaccines will likely be
just part of a larger treatment regimen — to mop up cancer cells after surgery
or chemotherapy, or reduce the need for chemotherapy or radiation in the first
place.
Reference: Lok, Corie (2003). “Booster
Shot against Cancer: Cautious optimism about the latest efforts to enlist the
immune system.” Innovation News, November.
Encouraging Anti-rejection Drug
The experimental organ-transplant anti-rejection drug CP-690,550 has shown
promise in mice and monkeys. It targets an enzyme produced only in immune system
cells, leaving other cells unharmed, unlike existing anti-rejection drugs. In
tests on monkeys, the drug delayed the rejection of transplanted kidneys for 70
days — 12 times longer than the six days of a control group that received no
immunosuppressants — and it did not appear to affect the monkeys’ metabolism.
Human transplant trials of the drug are being considered. Pfizer is already
testing it in patients with psoriasis, and it may work for other autoimmune
diseases including diabetes and rheumatoid arthritis.
Reference: Bhattacharya, Shaoni (2003). “Designer drug
halts organ rejection.” New Scientist, October 31 (citing Science vol 302 p
875).
Angiogenic Drug Disappoints
Despite less-than-hoped-for results from its latest trial, market analysts
seem to agree the experimental cancer drug Avastin could still receive
FDA approval by the end of March and be the first angiogenic drug to reach the
general market. (Angiogenic drugs inhibit blood flow to tumors, starving them to
death.) It could also be a “blockbuster,” with billions of dollars in annual
sales. (Perhaps it wil be one of the last blockbusters — see “Pharmacogenomics
Speed Bump” in the Acceleration section of this issue.)
Reference: Pollack, Andrew (2003). “Genentech’s
Cancer Drug Falls Short in a Second Round of Tests.” New York Times,
November 26.
Heart Disease Medicine & Imaging
A synthetic form of HDL or “good” cholesterol reduced plaque in coronary
arteries by four percent in the five weeks of a small-scale human trial. The
cardiologist who coordinated the trial was ecstatic, calling it “a paradigm
shift” in the treatment of cardiovascular disease. An American Heart Association
official admitted the findings were “very intriguing,” but cautioned they were
also preliminary.
Forty-seven heart disease patients received weekly infusions of either the
synthetic HDL or an inert placebo for five weeks. Arterial plaque was measured
using a new imaging technique, intravascular ultrasound (IVUS), regarded as an
invaluable tool for measuring drug treatment effects. A rotating probe, threaded
via catheter, bounces sound waves off coronary artery walls. IVUS converts the
reflected sound into images that distinguish between soft plaque and the harder
tissue of the vessel wall. Conventional coronary angiography, which uses X-rays,
would not have revealed the effect of the experimental drug because it detects
only plaque that narrows the lumen of the vessel, and such narrowing is “the
last thing that happens in the course of cardiovascular disease.”
This development illustrates the exponentiating symbiosis, so to speak, of
technologies (in this case, the symbiosis of molecular medicine and ultrasound).
It also adds to the evidence that technology could solve the growing crisis of
massive numbers of baby boomers reaching the age at which heart disease becomes
prevalent, putting intolerable pressure on healthcare costs.
References: Stein, Rob (2003). “Synthetic
‘Good’ Cholesterol Helps Clear Arteries. Small Study Indicates the Possibility
That Drug Therapy Could Reverse Heart Disease.” Washington Post, November 5,
p. A02.; Winslow, Ron (2003). “Method Gives
View of Artery Walls.” Wall Street Journal, November 5.
Heart Tissue Repairs
Preliminary results from a handful of studies of a (non-embryonic) cell
therapy for heart disease have been “tantalizingly promising,” reports Rob Stein
in the Washington Post. A Duke University Medical Center researcher was a bit
more upbeat: “For years . . . people said we were nuts. They said it wouldn’t
work. Now the field is finally coming of age — it’s exploding. This is a huge
shift in thinking about the potential to treat injured hearts.”
The method involved injecting or infusing immature cells from the patient’s
own leg muscles (myoblasts are preferred) or from bone marrow into the heart of
patients when they undergo bypass or artificial implant surgery. The cells, it
is thought, can turn into healthy heart muscle and, in addition, stimulate the
growth of new blood vessels. There is no risk of rejection.
A related technique under development uses drugs to stimulate immature cells
to migrate on their own out of the bone marrow, travel through the bloodstream,
implant themselves in the heart, and begin replacing damaged tissue. There is
even new evidence that the heart itself can generate immature cells that appear
able to grow into new muscle, so the hunt is on for a way to stimulate that
process in heart-attack patients.
In the trial patients, hearts started pumping more strongly after several
weeks, and follow-up tests indicated that the repair cells did indeed grow into
viable heart muscle in damaged areas. There were, however, indications that the
implanted cells could cause arrhythmias. Much larger studies are needed — and
planned — to confirm the viability of this therapy.
Reference: Stein, Rob (2003). “Seeding
Hearts With Healing Cells, Doctors Hope to Grow Muscle.” Washington Post,
November 6, p. A13.
Hepatitis C Under Molecular Attack
Hepatitis C virus (HCV), spread mainly by contaminated blood and only
isolated and identified in 1989, infects three million people annually and leads
eventually to severe liver damage or cancer in the vast majority of cases.
Though less deadly than AIDS, its higher prevalence, longer incubation period,
and the absence of effective drugs make it potentially a more lethal
epidemic.
A German drug company has demonstrated that a molecule called BILN2061 can
block an HCV protein and — at least temporarily — disable the virus. HCV
levels in a handful of patients given four doses of BILN2061 fell to almost
undetectable levels within two days, but rose slowly again when the treatment
stopped. It appears from experiments in monkeys that at high doses the drug
causes heart damage.
New cell-culture technologies are accelerating research into this and other
promising HCV drugs, such as an antisense compound that binds to the virus’s
genetic material and stops it reproducing, and a monoclonal antibody that blocks
a protein the virus uses to attach to its target cells. However, as with cancer
and HIV, no single medicine will likely be enough to beat HCV, and the cost of
HCV drug cocktails could leave the majority of sufferers still without hope.
Reference: Unknown (2003). “Hepatitis
C: Needles and haystacks.” The Economist, October 30.
Safer Ecstasy
Drugs that block the protein UCP-3 appear to restrain the sometimes fatal
rise in body temperature in people who have overdosed on the narcotic Ecstasy,
according to US research. However, UCP-3 is thought to convert stored muscle
energy into heat, and a similar protein in fat helps hibernating mammals stay
warm; therefore, drugs (like Ecstasy) that boost UCP-3 levels may actually help
to treat obesity by burning up energy stored in fat reserves.
One wonders whether making a narcotic safer will encourage its use. And given
the lengths to which people are known to go to lose weight, one wonders whether
the knowledge they can do so through a narcotic will also encourage its use.
Reference: Pilcher, Helen R. (2003). “Mutant mice chill out on
ecstasy: Drug to prevent lethal overheating may result from protein find.”
Nature, November 23.
FDA Approval Sought for Telerobotic Brain Implant
Trial
Following success in monkey trials, US startup Cyberkinetics Inc., founded by
the chairman of the Department of Neuroscience at Brown University, is asking
for FDA permission to conduct human clinical trials of its BrainGate
implant in paralyzed people, to enable them to type, control lights and heating
controls, maneuver wheelchairs, or even manipulate robotic limbs. A venture
capital firm backing Cyberkinetics sees a bigger potential market of people with
neurodegenerative diseases and elderly people who have lost certain functions
but have active brains.
BrainGate is based on work done at Duke University that enabled
monkeys to manipulate a robotic arm with their thoughts. It is a four millimeter
square chip with an array of a hundred tiny wires. The chip is punched, using a
spring-loaded inserter, into the surface of an area of the brain known to
control motor activity, and wired to a cable jack protruding from the skull,
where a computer can be plugged in to interpret the neuron firings detected by
the chip and act on them.
The phase I trial could begin early in 2004 be completed by the end of the
year.
Reference: Krasner, Jeffrey (2003). “Approval
sought to test brain implant: Neuron-fired device would aid paralyzed people,
state firm says.” Boston Globe, November 6.
Ebola Vaccine
In November, a US volunteer “stepped into medical history [by] becoming the
first person ever injected with an experimental vaccine designed to protect
against Ebola,” writes Rick Weiss in the Washington Post. The vaccine is
a synthetic DNA and “probably the safest and most sophisticated vaccine ever
made,” though that probability hardly detracts from the volunteer’s courage.
The vaccine contains no part of an actual virus, and is “spray-blasted”
through the skin, not injected via needle. It was engineered to stimulate an
immune response stronger than a real Ebola infection would cause, without
producing any symptoms of the disease itself.
The volunteer — a nurse — said “It’s so rare in research that you get to
help with something that’s so promising. And the pharmaceutical industry would
never do this. There’s no profit in this.” Given the potential for aerosolized
Ebola as a bioterror agent, and the US government’s willingness to spend heavily
on anthrax vaccine, he could be wrong about that.
The vaccine is made of synthesized strands of DNA that mimic those found in
the real virus, but with key components removed, including the part that
triggers illness and the part that might allow the DNA to recombine with the DNA
of some other virus to make a new and potentially disease-causing bug.
The DNA causes subcutaneous skin cells to produce Ebola proteins, to which
the immune system then responds, building long-term immunity should the proteins
reappear — which they will in the event of a real Ebola infection. Four
vaccinated monkeys were unharmed after being deliberately infected with Ebola,
while four not vaccinated all died. The human volunteer cannot be deliberately
infected with real Ebola as the monkeys were, so the researchers will simply
compare his immune responses with those that proved effective in the monkeys.
More volunteers are being sought for the expanded trials that must take place if
the vaccine is ever to be approved.
Reference: Weiss, Rick (2003). “Volunteer
Gets Experimental Ebola Vaccine.” Washington Post, November 19, p. A-1.
Behavior Monitoring
Machine learning, as well as human understanding, is being enhanced by
“behaviometric” software designed to understand the behavior of people, animals,
machines, or a combination of all three. The software developers must first
identify, measure, and describe the essential characteristics of a given
behavior quickly and easily — and that is difficult. It took Israeli
researchers almost 20 years to figure out how to identify people accurately by
their typing behavior.
The single biggest difficulty is the vast amount of information present in a
behavior or attribute, making filtering to eliminate irrelevant information
crucial. Sophisticated video surveillance systems might, for example, ignore
crowds of people walking next to a fence, but notice one person climbing the
fence. Behaviometric software has to be able to sift through “a bewilderingly
large number of object behaviors: water undulating in waves, boats moving
against the horizon, birds darting and soaring through the air, people strolling
on a beach,” says Erik Sherman in Technology Review.
It also needs to take into instant account — depending on its goal — the
size and/or speed and/or color and/or direction of an object . . . not to
mention the day of the week (does the garbage truck belong next to that bank on
a Sunday?) and so on.
A US company, Living Independently, makes a behaviometric system that watches
elderly people living at home, alerting family or health professionals if
behavior suddenly changes. Infrared sensors note when someone gets up,
approaches a food preparation area, opens a medicine cabinet, and enters the
bathroom. The information is relayed over an ordinary phone line to computers
that compare the behavior to what the system considers “normal” for the person
based on previously collected data. Sudden changes in behavioral patterns
trigger alerts to caregivers. Living Independently’s behaviometric software
incorporates machine learning and is able to learn when a behavior change is
normal, so as to minimize false alarms.
The President’s Council on Bioethics is concerned about the use of current
and forthcoming behavior-modifying drugs by parents on children — not to
correct a medical problem, but to “improve” their child’s performance in some
way. One wonders about the ethical implications when behaviometric software
expands into regular family households and schools, and into the brain impant
chips mentioned elsewhere in this section.
Reference: Sherman, Erik (2003). “Behavior-Monitoring
Machines.” Technology Review, November 12.
See also “Robots that
Sense” and “Industry
Forming Around Self-care” in previous issues of Health Futures
Digest. |
