If a DNA therapy that enabled paralyzed mice to walk
again succeeds in humans, the robotic exoskeletons mentioned in the
Robotics section may not be needed. And if a robot
taking over the delicate job of threading thin wire through tiny veins to
power and control cardiac resynchronization implant devices succeeds, the human
surgeon may not be needed either.

Experimental drugs have been much in the news:

• One derived from Gila spit appears to control blood
  sugar in type-2 diabetics andreduces their weight, as a bonus.
• Another has significantly reduced heart tissue
  damagein mice given induced heart attacks.
• Early tests of another, to reduce chronic
  rejection syndrome in transplant patients, were enough for an American
  Hospital Association official to call it a potentially bigger deal than
  cyclosporine was when first introduced.
• And an experimental drug has completely protected lab rats from the ravages
  of inhalational anthrax, and improved survival rates in
  rabbits and monkeys. 

  These, and the recent or imminent arrival of several potential blockbuster drugs, may require redefinition of what
  counts as “blockbuster.”

  In other news:

   

• Nanoparticles of a ceramic material have enabled brain cells to live four times longer. 

   

• A totally non-invasive, ultrasonic surgery is
  capable of removing cancers very precisely and with rapid patient recovery.
  Running counter to the trend to non-invasive surgery, however, is a procedure
  that removes a patient’s heart for extracorporeal
  surgery. And animal tests have begun of bioengineered heart
  muscle patchesfor intra- or extracorporeal heart surgery. 

   

• Biodegradable polymer stents under development will
  likely become an alternative to today’s permanent metallic stents. 

   

• Genetically modified vaginal bacteria have succeeded in destroying the AIDS virus, in test-tube experiments. Success
  in human trials would herald a major advance in infectious disease prevention. 

   

• Add “womb” to the nearly full list of bioengineered
  artificial body parts, one of which is bone. A growing child has received an
  artificial limb bone that grows with him. 

Human trials will begin next year of a multiple sclerosis therapy that has
enabled paralyzed mice to walk again. “There isn’t a mouse we haven’t cured,”
says its developer. The therapy is part of a new class of autoimmune disease
vaccines that offers renewed hope for MS, type 1 diabetes, and rheumatoid
arthritis patients, and it may even be possible to reverse existing joint
damage.

The vaccines are engineered from two DNA molecules, and work by shutting down
the rogue immune cells that are the proximate cause of these diseases. One
molecule encodes a protein that acts as bait for the rogue immune cells, the
other then encodes a protein that switches the rogue cells from destructive to
protective mode.

The Stanford University Medical Center immunologist and neurologist who
developed the approach has raised $14.5 million in first round financing. It may
take seven years before the vaccine is approved.

Reference: Jonietz, Erika (2003). “Target:
Rogue Immune Cells — DNA-derived vaccine advances on MS.” Innovation,
September.

Gene Therapy Used for Parkinson’s

Gene therapy has been used for the first time to treat Parkinson’s. The
procedure has been approved by the FDA for a Phase 1 (safety) trial involving 12
severe cases. It involves boring a hole in the skull to infuse 3.5 billion viral
particles, each bearing a copy of a human gene thought to help relieve tremors,
shuffling gait, and other symptoms of Parkinson’s, into the brain. There is
concern about the absence of evidence from primate testing, and the possibility
of the carrier viruses getting out of control.

Reference: Grady, Denise; and Gina Kolata (2003).
“Gene Therapy Used To Treat Patient With Parkinson’s.” New York Times, August
19, p. A-1.

Potential Stem Cell Therapy for Parkinson’s

Mice suffering a condition similar to Parkinson’s disease were cured after
receiving brain implants of tissue grown from embryonic stem cells harvested
from cloned mouse embryos. This was not the first such attempt, but it was the
first to use cells from a clone of the patient, ensuring a perfect genetic match
and eliminating the need for treatments to suppress the immune system. The lead
researcher told the BBC that the study was “proof of principle” that cloned
embryonic stem cells could be reliably transformed into a variety of useful cell
types, with potential applications in many disease types.

There remain major technical and possibly insurmountable politico-ethical
issues to resolve before such a technique could be tested in humans.

Reference: Unknown (2003). “Mouse cloned to
cure Parkinson’s.” BBC News, September 21.

Stem Cell Therapy Cures Blindness

A man almost totally blind for 40 years following a childhood accident has
had some vision restored by corneal and limbal stem cells transplanted into his
one remaining eye (the other was lost in the accident). Five months after
surgery, he could perceive slight movements and recognize simple shapes. Two
years after the surgery, he can see form, color, and motion almost normally,
though he still has difficulty perceiving depth and recognizing faces and
objects.

Reference: Unknown (2003). “Cell transplant
restores vision: A blind man can see again after being given a stem cell
transplant.” BBC News, August 25.

Lizard Spit for Diabetes

Arizona’s Gila monster, a lizard that eats only about four times a year, has
evolved salivary secretions to control massive surges in blood sugar levels
after a meal. The experimental drug exenatide, derived from that saliva,
is reported to control type-2 diabetic patients’ blood sugar levels and reduce
their weight.

Forty-four percent of 155 Phase III trial patients who had not responded to
established diabetes drugs metformin and sulfonylureav not only
achieved glucose level averages within the target range, but also lost on
average 3.4 kilograms (7.5 pounds).

The drug is expected to reach the FDA for approval in 2004.

Reference: Reuters (2003). “Lizard
spit drug controls diabetes and cuts weight.” Forbes, August 25.

Minimizing Damage from Heart Attacks

An experimental drug to reduce tissue damage from heart attacks has achieved
positive results in rats over several months, saving a reported 56 percent of
heart tissue at risk, and with no significant side effects. Large-animal testing
is now planned, with results expected by year’s end. Human clinical trials are
expected to follow 12 to 15 months later with a second-generation drug twice as
potent as the prototype.

Reference: Sing, Terrence (2003). “Biotech
takes heart in potential of new drug.” Pacific Business News, August
15.

Extracorporeal Heart Surgery

Surgeons at the University of Maryland Medical Center recently removed a
patient’s heart to a bucket of ice in order to once-and-for-all excise a
recurrent myxoma tumor from it. After the harmful cells were removed, bovine and
human donor tissues were used to rebuild the heart’s upper chambers. The patient
was kept alive during the operation by a heart-lung machine.

References: Craig, Tim (2003). “Woman’s
heart removed, rebuilt, replaced: Surgeons use cow tissue to reconstruct
tumor-damaged area.” San Francisco Chronicle, August 29; Craig, Tim (2003).
“Woman’s
Heart Is Removed, Rebuilt U-Md. Surgery Fights Tumor.” Washington Post,
August 29, p. B01.

See also the February 2003 issue of HFD for
another
report of extracorporeal techniques.

Heart Patch

The National Institutes of Health has awarded nearly $5 million to
researchers to conduct animal tests of bioengineered blood vessels and cardiac
muscle patches. The tissues are first grown, using adult stem cells on a
biodegradable, flexible, and porous polymer scaffold. Then they have to be
mechanically engineered and stressed to build up their strength and put them in
the correct orientation for contraction, before being transplanted into lab
animals.

The researchers caution that it has not yet been established that muscle or
bone marrow stem cells can generate specialized cardiac muscle cells, or if the
cells that are generated will be sufficient to improve overall heart function.

Reference: Srikameswaran, Anita (2003). “Local bioengineers want
to build patch, blood vessels for heart.” Pittsburgh Post-Gazette, August
5.

Robotic Pacemaker Implanter

A robotically enhanced cardiac resynchronization technique adds to the
toolkit of minimally invasive procedures. A biventricular pacemaker or
implantable cardioverter defibrillator (ICD) involves the threading of wires
through veins into the ventricles and securing them to the chamber walls. Though
minimally invasive, it is a time consuming procedure and sometimes impossible if
the veins are too small.

Belgian surgeons have tested an endoscopically monitored, voice-activated and
hand-operated robot with tiny “hands” able to work at much smaller scales than a
surgeon’s hands. Their study found the method to be safe and reliable, causing
less pain to the patient, less surgical trauma, and a shortened recovery time.

Reference: Unknown (2003). “Researchers
test robotic technique for biventricular pacemakers.” HeartCenterOnline,
August 15.

Immunosuppressant Advance

Preliminary results from a study of the drug everolimus, approved in
Europe but not in the US, suggest that it can prevent or reduce chronic
rejection syndrome, aka “transplant disease,” a condition that can fatally
affect heart-transplant patients. An American Heart Association official said
the discovery could be as big as that of the first anti-rejection drug,
cyclosporine, which made transplants feasible. But he cautioned that even
after it receives FDA approval, it will still take years to assess its true
efficacy as a long-term treatment. The study involved 634 patients at 52 clinics
in North and South America, and Europe.

Reference: McConnaughey, Janet (2003). “New drug
holds promise for heart-transplant recipients.” Associated
Press/Philadelphia Inquirer, August 28.

Lab to Production in a Heartbeat

Stent-maker Guidant Corp. has acquired an exclusive-use license for
bioabsorbable polymers, specifically designed for vascular use, to be used in
“next generation” bioabsorbable stents that will replace today’s metallic
stents, which typically stay in place for a person’s lifetime. Guidant has
tested the experimental polymer in drug-coated stents on patients and its
performance is encouraging, the company said.

Reference: Swiatek, Jeff (2003). “Guidant
Corp. buys technology for new stent.” Indianapolis Star, September
3.

Living Condom

In test-tube experiments, natural vaginal bacteria have been successfully
genetically enhanced to destroy the AIDS virus, and the work is now moving
forward into primate tests. Although vaginal medications can be applied for the
same purpose, they damage the mucus membranes of the vagina, making it more
susceptible to other infections. The bacteria were genetically engineered to
secrete a protein to which HIV attaches in order to break into cells. They
completely blocked laboratory strains of HIV from infecting human cells, and
blocked an HIV strain taken from actual patients by more than half.

If it succeeds in human trials, and if nations that already reject
genetically modified food can be persuaded to allow genetically modified
therapies, the method would not only be a powerful weapon in the war on AIDS,
especially in countries where males refuse to use condoms, but also could be
modified to protect against other infections.

Reference: Cohen, Philip (2003). “‘Living condom’
could block HIV.” New Scientist, September 03.

Artificial Womb

A Cornell University researcher recently made an artificial womb shaped like
a uterus out of a biodegradable scaffold of collagen, then lined it with
endometrial cells from a uterus, dosed them with hormones and nutrients, and
introduced embryos, which attached themselves to the walls and began digging
into the wall in search of blood vessels, as they would in a natural womb. The
experiment ended there, so it is not known if the embryos might have carried to
term if nourished with a blood supply. (It is also not clear from the article
whether the experiment used human or animal components.)

Nevertheless, mammalian ectogenesis — the nurturing of an embryo in an
external womb — is now conceivable, though immense difficulties remain to be
overcome.

Reference: Bailey, Ronald (2003). “Babies In a Bottle: Artificial
wombs and the beginning of human life.” ReasonOnline, August 20.

Monoclonal Antibody for Anthrax

Deadly toxins released by the Anthrax bacterium can evade antibiotics. Human
Genome Sciences has now developed a highly specific monoclonal antibody that can
bind to an anthrax agent and stop the toxins from developing. A single injection
completely protected laboratory rats, and it improved the survival rates of
rabbits and monkeys exposed to inhalational anthrax. Human clinical trials are
not possible, since it is unethical to expose humans to a bioterror agent for
research purposes, but the FDA may approve drugs based on animal efficacy
studies alone.

Reference: Chase, Marilyn (2003). “Human
Genome Says It Created Anthrax Antibody.” Wall Street Journal, September
15.

Longevity: Nanotech On the Brain

A biologist and an industrial chemist have accidentally discovered that
industrial ceramic nanoparticles can prolong the life of brain cells by three to
four times. On a whim, they set out to explore what would happen if brain cells
absorbed nanoparticles of cerium oxide, a ceramic material being developed as a
coating for high-temperature machine parts. Nothing did seem to happen, and some
petri dishes containing the mixture were forgotten for three months, by which
time the brain cells should have been dead for two months. Serendipitously, the
researchers discovered that the brain cells were not only still alive, but still
functioning — “still talking up a storm to each other.”

The nanoparticles appear to act like an antioxidant, mopping up free radicals
that cause the cell damage that in turn causes aging. A molecule of the
antioxidant vitamins C or E stops working when it has scavenged one free
radical, whereas one cerium oxide nanoparticle regenerates itself inside the
cell and in theory could scavenge all the free radicals. The nanoparticles were
also found to have a potent anti-inflammatory effect.

The potential is enormous, and the scientists have been awarded a substantial
grant from the NIH to pursue the work. It could be used in treatments for
aging-related diseases such as Alzheimer’s and Parkinson’s, an anti-inflammatory
coating for stents, and to reduce neural damage from head injury or stroke. But
it is “five to 20” years away from use in humans.

Reference: Lundine, Susan (2003). “Tiny
tech leads to big grant, NIH interest.” Orlando Business Journal, September
5.

See also articles on “Longevity” in the
Acceleration and Policy sections of this issue.

New Approaches to Cholesterol Drugs

Time was when a blockbuster drug could capture a market for decades, with
nothing to worry about but patent expiration and the arrival of generics.
Acceleration means that those days are over. Take statin-based drugs that stop
the liver from producing cholesterol, for example. A potent new statin drug,
Crestor, could soon be giving $10 billion per annum Lipitor a run
for its money.

The FDA also recently approved one new non-statin drug, Zetia, that
works in conjunction with statin drugs to lower low-density lipoprotein (LDL),
while a whole new class of drugs called ACAT (acyl-CoA cholesterol
acyl-transferase) inhibitors is under development. The ACAT inhibitor
avasimibe is already in clinical trials. Another new class, that targets
high-density lipoprotein (HDL) instead of LDL, has also resulted in a trial drug
called torcetrapib. Another, particularly powerful, HDL drug appeared to
clear the arteries of some very sick patients. Yet another experimental drug,
AGI-1067, hopes to reduce heart disease by lowering cardiac inflammation.

Reference: Herper, Matthew (2003). “Pharmaceuticals:
Forget The Statins.” Forbes, August 14.

Replacement Limb Bones

Artificial bones made of titanium have to be replaced frequently in a growing
child. The FDA recently allowed a boy suffering from Ewing’s sarcoma to receive
a new upper-arm prosthetic bone that can be non-invasively lengthened as he
grows. The Repiphysis prosthesis is made of a polymer that softens when
heated by an electromagnetic ray, then stretches — up to a third of a
centimeter in 20 seconds — under the force of an internal spring, and finally
stays in the lengthened state when it cools.

Reference: Cho, David (2003). “Youth’s
Artificial Arm Will Grow With Him: Arlington Bone Cancer Patient Becomes a
Pioneer for Expandable Prostheses.” Washington Post, September 3, p.
B02.

Ultrasound Cancer Surgery

In August, doctors at Brigham and Women’s Hospital totally destroyed a female
patient’s benign, but softball-sized, fibroid tumor by focusing a high-intensity
ultrasound energy bean on it. The procedure was definitively non-invasive — no
incisions, no sutures, no bleeding.

Already approved in Europe and Israel, the procedure could receive FDA
approval early next year, and will give US women who suffer from fibroids an
alternative to hysterectomy.

The patient, who remains conscious during the procedure, lays in an MRI
machine, which not only shows the surgeons the precise location of the tumor but
also gives a constant readout of the temperature at each spot of the fibroid as
that spot is hit by a 20-second ultrasound burst, initiated by the click of a
mouse.

This patient’s tumor required about 50 such hits. Immediately following the
three-hour procedure, she felt some mild cramping but was able to walk two
blocks to a restaurant and eat lunch.

The technology could eventually be applied to other types of tumors, even
malignant brain tumors. Experiments on prostate and breast tumors are already
underway.

Reference: Goldberg, Carey (2003). “Fighting
tumors with beams: Ultrasound technology gets Boston hospital test.” Boston
Globe, August 1, p. A1.