Home' Technology Review : January 2005 Contents 84
Genetically engineered bacteria treat
: Finding ways to get drugs to the right part of the body
is a constant challenge for drugmakers. The intestines would
seem easier to treat than other areas, as dr ugs taken orally should
eventually arrive there. But a number of promising drugs for the
treatment of colitis, an intensely uncomfortable in ammation of
the large intestine, become waylaid in the mucus of the small in-
testine and never reach their target. Now, a group of researchers
led by Lothar Steidler from Ghent University in Belgium has ge-
netically modi ed bacteria to secrete such a drug as they travel
through the gut.
: The resea rchers engineered Lactococ-
cus lactis so that it would produc e trefoil factor s, sha mr ock-
shaped proteins that hasten healing and protect the gut from
injury. The modi ed bacteria proved more e ective than the
puri ed protein alone at preventing a nd treating colitis in mice.
Outside the body, the bacteria do not sur vive.
: The use of genetically modi ed (GM) organ-
isms as dr ug delivery devices is moving toward the mainstream.
Another GM bacterium produced by these researchers, one that
secretes the anti-in ammatory drug interleukin-10, is being
tested in European clinical trials as a treatment for in ammatory
bowel disease. Other GM bacteria, to be delivered to the nose and
vaginal tract, are being studied to prevent infectious disease. Still
another may deliver a cancer vaccine. In the 1980s and 90s, re-
combinant DNA technology ushered in an era of new protein
dr ugs; despite substantial regulatory and technical obstacles,
bacteria may prove an e ective way to deliver them.
Source: Vandenbroucke, K. et al. (2004) Active delivery of trefoil factors by
genetically modi ed Lactococcus lactis prevents and heals acute colitis in mice.
Neuronal damage has a new culprit
: Strokes kill neurons by depriving them of oxygen.
Without oxygen, neurons have di culty producing the molecule
ATP, their source of energy. This prevents them from perfor ming
housekeeping chores, including the important task of pulling
glutamate, a message-transmitting chemical, back into the neu-
ron after its message has been received; glutamate keeps sending
signals to neighboring neurons, resulting in a deadly in ux of cal-
cium ions. However, drugs designed to curb stroke damage by
blocking glutamate s e ects have shown disappointing results in
clinical trials. New research, led by Zhigang Xiong at the Legacy
Clinical Research and Technology Center in Portland, OR, shows
another strategy that seems more promising.
: To make ATP without oxygen, cells use
an ine cient method that produces lactic acid and protons as by-
products. Neurons using this method become more acidic; they
also become more susceptible to damage, but it wasn t clear why.
Xiong and his colleagues speculated that acid-sensing ion chan-
nels (ASICs) might move calcium into the cell, thereby accelerat-
ing neuronal damage. After showing that strokelike conditions
activated ASICs, and that ASICs allowed calcium into the neu-
ron, they studied mice lacking the gene for ASIC1a, which is
highly expressed in the brain. When subjected to simulated
strokes, mice without the gene fared better than mice with it,
even when treated with memantine, a drug that blocks the ac-
tions of glutamate. The researchers also discovered that small
molecules that block ASICs can protect against stroke injury. In
rats treated with one such molecule before simulated strokes,
the rate of neuronal death was less than half that among un-
: Drugs that block ASICs will likely face many of
the same challenges as those that block glutamate: they must be
administered quickly after a stroke and could have unintended
e ects on brain function. Nonetheless, small molecules have al-
ready shown the capacity to prevent the type of brain damage
caused by this newly described mechanism. Thus, these results
o er hope against a devastating cause of disability and the third-
leading cause of death in the United States.
Source: Xiong, Z. G. et al. (2004) Neuroprotection in ischemia: blocking calcium-
permeable acid-sensing ion channels. Cell 118: 687-698.
Carbon nanotubes stretch out
: Little more than a nanometer wide, carbon nanotubes
have become superstars of the nano world: unusually strong,
electrically conductive, and stable at high temperatures. Fibers
composed of nanotubes should outperform those made from
any existing material. However, the length of the tubes---most are
only tenths of a millimeter long---requires that they be lined up
for peak performance. Now, researchers at Los Alamos National
Laboratory and Duke University have created nanotubes that
are centimeters long, and whose length is checked only by the
size of the chamber used to create them.
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