| Brain Imaging
Non-invasive, radiation-free brain scans such as functional magnetic
resonance imaging (fMRI) allow researchers to look inside a child’s developing
brain, not only to better understand functions such as language processing but
also to see the effects of specific interventions on a problem such as a speech
disability. It has also shown just how “plastic” (malleable) is a child’s brain
compared to the adult brain, which is literally “set in its ways.”
A recent fMRI study, reports Christopher Windham in the Wall Street
Journal, suggests that brain imaging could be used to “tell whether a
toddler who has nothing to say suffers from serious language problems or is just
slow to talk, as many perfectly normal kids are,” and therefore determine the
need (or not) for speech-language therapy. Brain imaging can then tell whether
or not a given therapy is working simply by comparing “before and after” scan
images.
Alzheimer’s Breakthrough
Imaging technology is also set to help diagnose Alzheimer’s disease in
people, Windham reports in another Journal article. A radioactive dye
called Pittsburgh Compound B (developed at the University of Pittsburgh)
attaches itself to the beta-amyloid protein plaques thought to be a major factor
in Alzheimer’s (either as the cause or at least a sure symptom of the disease.*)
A PET scan then reveals the location and quantity of any amyloid plaques
present.
Like the fMRI method described above, the Pittsburgh development is a
breakthrough not just in diagnosis but also in monitoring the effectiveness of
treatments, assuming the preliminary success is confirmed. Other imaging methods
under study include MRI measurements of brain shrinkage in patients, PET scans
to track mild cognitive impairment, and PET scans to detect amyloid plaques
using a molecule called FDDNP developed at the University of California at Los
Angeles, that adheres not only to beta-amyloid but also to neurofibrillary
tangles.
* The latest research strongly suggests cause. See
“Alzheimer’s Cause Identified?” below.
Reference: Windham, Christopher (2004). “Brain
Imaging Provides A Window on Speech And Learning Problems.” Wall Street
Journal, January 23.
Reference: Windham, Christopher (2004). “Test
Detects Alzheimer’s Marker.” Wall Street Journal, January 22.
Alzheimer’s Cause?
There is now strong evidence that amyloid beta plaques are a cause rather
than just a symptom of Alzheimer’s disease. Northwestern University researchers
genetically engineered a strain of Alzheimer’s-prone mice to eliminate an enzyme
involved in amyloid beta production, and found that the treated mice were less
prone to dementia and there were no noticeable side effects. Drugs that block
the enzyme in humans exist, but have yet to be tested in humans.
Besides its relevance to Alzheimer’s, the research “clearly shows the
benefits of using genetically modified animals in the research of
difficult-to-study neurological conditions,” notes Helen Pilcher in
Nature. See “Children vs. Pets” in the Policy section for an
interesting take on the subject.
Reference: Pilcher, Helern R. (2004). “Alzheimer’s disease cause
identified? Amyloid beta protein may trigger mental decline.” Nature,
January 8 (quoting Ohno, M. et al. “BACE1 deficiency rescues memory deficits and
cholinergic dysfunction in a mouse model of Alzheimer’s disease.” Neuron, 41, 27
– 3, (2004).
Stem Cell Therapy
Embryonic (and a few adult) stem cell therapies are being developed for a
variety of major diseases. Embryonic stem cells can be created by cloning or
parthenogenesis. Cloning is ethically unnaceptable, at least in the US, making
the parthenogenetic approach that much more appealing. Advanced Cell Technology
(ACT)’s CEO has confirmed a Wired report (covered in last month’s Digest)
that his firm has created stem cells through parthenogenesis, although ACT “has
yet to publish the current research in a peer-reviewed journal, and the firm is
known to be searching for funds,” cautions The Economist.
Nevertheless, parthenogenesis is reliably churning out monkey embryonic stem
cells, and a Michigan State University researcher has coaxed them into forming
various cell types, including nerve cells that produce dopamine, whose
deficiency leads to Parkinson’s. The next step will be to test them in monkeys.
Going from successful animal tests to successful human tests has long been
problematic, but scientists are beginning to understand how they might avoid
that problem in the case of stem cell therapies. Human embryonic stem cells are
cultivated in test tubes which also contain so-called “feeder” cells that
somehow prevent the stem cells from differentiating too soon into mature cell
types. To date, mouse cells have been the feeder cells of choice for human
embryonic stem cells, but there are fears that mouse feeder cells could transmit
viruses to the human stem cells, making it “unethical to expose human subjects
to stem-cell lines that have been derived with mouse feeder layers,” in the
words of a recent report.
One alternative may be to use human feeder cells. A Singapore researcher has
discovered that adult skin cells work just as well as mouse feeders. Another
alternative is to dispense with feeder cells altogether. A US-Greek-French team
has had some success in cultivating human embryonic stem cells for several
generations using a chemical instead of feeder cells.
The need for new embryonic stem cells lines in the US is exacerbated by the
fact that only a dozen or so of the 60 lines that qualify for federal research
dollars under Bush administration restrictions are actually available and
usable, and that in any case all the approved lines were grown using mouse
feeder cells and are therefore risky.
A further problem recently reported is that human embryonic stem cell lines
grown over several months in the laboratory can develop genetic abnormalities
and the stem cells could, in theory, turn into cancer cells.
What keeps researchers battling the obstacles is the mounting evidence that
stem cell therapy can work. Recently, for instance, Israeli researchers
succeeded in coaxing test-tube human embryonic stem cells into becoming the
various cell types that make up blood vessels. When injected into “special
experimental mice,” the differentiated cells formed fully functional blood
vessels that joined up with the animal’s own circulatory system. This has great
potential for heart disease.
Reference: Unknown (2003). “Baby
steps: New work shows the promise, and pitfalls, of embryonic-stem-cell
research.” The Economist. December 30.
Prevention at the Source: Healthy
Insects
If, like Europe, you worry about the dangers of environmental contamination
and mutation from genetically modified crops, you may have nightmares about the
prospect of genetically modified insects. The prospect is very real: Scientists
are genetically modifying silkworms to produce pharmaceuticals instead of silk,
honeybees to resist pesticides, mosquitoes immune to malaria, and mosquitoes to
deliver vaccines instead of viruses through their bite — to name but a few.
A new report from the Pew Initiative on Food and Biotechnology warns that the
designer insects could be released into the environment before the US government
has had time to study the enormously complex issues (made even more complex by
being international) and craft appropriate guidelines and regulations. For
example, although mosquitoes immune to malaria sounds like a great idea given
that millions die of the disease every year, that immunity could render the
mosquitoes more likely to transmit other fatal diseases.
The report highlights the fact that research and its outputs are accelerating
faster than our ability to study and predict the ramifications.
Reference: Gillis, Justin (2004). “Making
Way for Designer Insects Risks and Benefits of Gene-Altered Bugs Merit Thorough
Study, Report Says.” Washington Post, January 22.
Universities Become Pharmas
Counter-intuitively, the acceleration in biomedical discoveries in recent
years has been accompanied by deceleration in the number of new drugs approved
annually in the US by the FDA — down from 53 in 1996 to 17 in 2002 and 20 in
the first 11 months of 2003, reports Sharon Begley in the Wall Street
Journal. In part, a reason may be that the drug companies are increasingly
interested only in blockbuster drugs that recoup their high cost of development.
Apparently, cost does not daunt the growing number of universities and hospitals
getting into the drug development business as feeders to the drug companies, in
an effort to see that their basic research on drugs is not wasted and may indeed
produce revenue.
St. Jude’s Children’s Hospital has built a US$40 million drug development
facility, and Stanford University has joint ventured with SRI International and
the University of California in PharmaStart, whose name sums it up. UC San Diego
already has a venture that links its drug researchers with venture-capital
firms. $40 million is not much compared to the approximately $1 billion cost of
producing a blockbuster.
St. Jude is planning small-scale production of an experimental AIDS vaccine
for small-scale phase I and II (safety and efficacy) clinical trials. Drugs that
have passed phase II trials can bring royalties of up to 40 percent from a
pharmaceutical licensee. It is also planning to produce a monoclonal antibody to
treat neuroblastoma (the second most common brain cancer in children), a protein
that would target leukemia, and gene therapy for hemophilia. Begley reports that
there is intense interest among other academic medical centers in the St. Jude
model, which bodes well for getting the acceleration of new drug introductions
back on track.
Reference: Begley, Sharon (2004). “Researchers
Try to Cut New Path to Pharmacy.” Wall Street Journal, January 12.
Repair of Leaking Lungs
Spiration Inc. is anticipating US Food and Drug Administration (FDA) approval
by May of its VALR Surgical System for minimizing air leaks in the lungs
of emphysema patients, reports John Cook in the Seattle
Post-Intelligencer. The device “uses vacuum pressure to capture diseased
tissue, sealing the lung in a sleeve that prevents air leaks,” he writes. The
company is also developing an intra-bronchial valve to limit ventilation in the
diseased part of the lung. About half of emphysema patients spring air leaks
after surgery, resulting in extended hospital stays, increased health care costs
and greater chances of death, he says. The American Lung Association puts the
number of emphysema deaths at 16,700 in the US in 2000, with 13.3 million people
being diagnosed and costing the nation $32.1 billion.
Reference: Cook, John (2004). “Millions
raised for tools to transform lung surgery.” Seattle Post-Intelligencer,
January 7.
Cosmetic Cryosurgery
A relatively new device already on the market could replace the “face lift.”
The ThermaCool heats the lower layer of skin cells while simultaneously
cooling the top layer. The heat-damaged deeper layer causes the skin to tighten.
The head of the American Society of Plastic Surgeons task force on emerging
trends told Wired‘s Kristen Philipkoski that the device would not replace
standard face lift surgeries, but it might postpone them or be used after
surgery to fine-tune the results.
The device’s maker told Philipkoski the full effect of the treatment peaks at
around six months and lasts for at least two years (maybe longer), and a full
facial treatment typically costs about $3,000. The brief pain is less severe
than that of laser resurfacing or a chemical peel but still enough to require
local anesthesia for treatment of any more than a very small area of skin, and
there is virtually no visible damage or recovery time.
ThermaCool is approved for the entire face in Canada and Europe, but
only for the upper face in the US. However, doctors are permitted to use it on
other parts of the body and some are treating the neck, stomach, arms, and
breasts. Its makers are hoping for FDA approval for tightening aging tendons and
connective tissue.
The US$40,000 cost of the device is less than millions of people pay for a
luxury car in the US, and given that it is new on the market, its price will
likely fall as sales pick up and especially when competitors come out with
improved versions. How long before people start buying such devices for the
home?
Reference: Philipkoski, Kristen (2004). “Wattles: Beware
the ThermaCool.” Wired News, January 26. |
