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Digital Medicine
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St. Louis
companies are racing to make medicines from the secrets of the genome.
By Chris Brown
Although St. Louisians often quietly lament the distance their city
seems to stand from center stage of world events, they do so in
ignorance of the city’s vital role in one of the most momentous,
portentous, potentially life-transforming scientific projects of
this or any time: the human genome project.
The human genome project, of course, is the effort to break the
code of the human DNA sequence and find there the blueprint to human
life, the instruction manual to the human animal.
A major milestone in this effort was reached in June 2000 with the
decoding of the first complete human DNA sequence.
And a major contributor in the effort has been the Genome Sequencing
Center at the Washington University School of Medicine.
Attempts to imagine how our lives will be changed by the knowledge
being gained from this project seem to veer quickly into the realm
of science fiction—indeed, the entire project is flavored with the
tang of Dr. Frankenstein.
But at the heart of the tale is the promise of entirely new and
powerful ways of understanding—and conquering—human disease and
deformity.
Of course, the road from promise to fulfillment is long, and must
be traveled by pioneers, some of them far removed from the well-funded
precincts of university laboratories.
Among the pioneers trying to shake early fruit down from the tree
and produce tangible advances from the genome project are a number
of St. Louis companies involved in taking the new kinds of knowledge
from the project and turning it toward the development of new drugs
and new therapies.
DzGenes LLC is a St. Louis biotech startup focusing its attention
on two important ways that the information from the human genome
project can improve the development of drugs, says CEO Terry Kungel.
The first is the imposing-sounding field of “population genomics,”
which Kungel says should help refine drug development through the
use of “disease associations,” an area of specialty for DzGenes.
Disease associations are carefully established patterns of correlation
between diseases and genetic abnormalities, Kungel says.
DzGenes has established 336 such associations thus far through close
genomic analysis of human blood samples in the company’s database.
Ninety-six of the associations involve kidney diseases, an area
the company will concentrate upon, Kungel says.
Such associations are particularly valuable to large pharmaceutical
companies under constant pressure to come up with new drugs to fuel
the growth expectations of Wall Street.
“These associations identify potential therapeutic targets,” Kungel
says. “They narrow the field that the large companies have to look
in to find new potential drugs.”
Another area of interest to Kungel and DzGenes that may yield fruit
a little farther down the line is the possibility of more narrowly
tailoring the development of drugs to groups with specific genetically
defined characteristics, or even to individuals.
“Drugs are developed now according to a one-size-fits-all model
that we know produces drugs that don’t fit everyone,” Kungel says.
“We lost around 100,000 patients last year alone to adverse drug
reactions.
“But if we can develop this idea of establishing associations between
adverse reactions and specific genetic types or characteristics,
then we can provide warnings, and look for ways to modify drugs
for specific types, and end up with treatments that are much more
effective.”
Another St. Louis company involved in turning the new understanding
of the human genome into new approaches to disease is Symbiontics
Inc., which is involved in exotic-sounding research on the use of
living organisms as drug-production and -delivery systems within
the human body.
The drugs in questions are proteins, according to Jon LeBowitz,
vice president of research for Symbiontics. Proteins, which are
long and complex polymers of amino acids, are difficult and expensive
to manufacture using traditional drug-production methods.
But as difficult as it may seem to believe, these very difficult-to-produce
proteins can in fact be produced by re-engineered versions of microorganisms
that are commonly found in the human bloodstream.
And if you can do the re-engineering work on a microorganism that
already goes by its own internal script to the very site in the
body where the protein is needed, then you’re really ahead of the
game.
The microorganism that Symbiontics has focused its attention upon
is called Leishmania, which enters the bloodstream through the bite
of the sand-fly and travels by its own gryoscope to a cell compartment
called the lysosome.
Although the effects of the leishmania organism on the body are
usually minor, by coincidence the target of the organism, the lysosome,
is the site of a group of relatively rare but most often fatal diseases
called Lysosome Storage Diseases.
The diseases are caused by a genetic defect, LeBowitz says, the
absence from the lysosome of a protein that is needed for the breakdown
of large molecules.
The best known of such diseases is probably Tay-Sachs disease, which
affects those of European Jewish descent disproportionately.
The fact that the Leishmania organism travels directly to the site
that is at the origin of these diseases makes it a perfect potential
delivery vehicle for a therapy for the diseases, LeBowitz says.
But the knowledge contained in the human genome—and in the Leishmania
genome, which has also been decoded—has opened up the possibility
of an even more radical approach than just using Leishmania as a
UPS service.
Using the detailed knowledge of the organism and the human body
contained in the two genomes, researchers at Symbiontics propose
to transform the Leishmania organism into a factory for the human
body that will produce exactly the protein missing from the lysosome
in sufferers of lysosome storage diseases.
“Having the knowledge of the genome is necessary to what we do,”
LeBowitz says. “It’s the knowledge we are building from to attenuate
the Leishmania and to build the protein. The genome has the instructions
we need.”
A third St. Louis company working to bring practical results from
the study of the human genome is Compass Genomics Inc.
But Compass is doing it in a different way, by trying to provide
other companies the tools and expertise needed to handle the new
information revolution in the world of biomedical research.
“We’re a full-service bioinformatics data-management company,” says
Richard Lesh, president of Compass Genomics.
“We provide a complete infrastructure, including hardware, software,
training and consulting, to help our clients deal with the new demands
of this field.”
The customers of Compass Genomics will be medium-sized “discovery
companies,” companies engaged in the hunt for new drugs that are
faced with data overload from their projects.
“Big pharmaceutical companies already have the infrastructure in
place, and the two-man shops can probably deal with their information
problems,” Lesh says. “But the medium-sized companies will be able
to leverage our infrastructure and expertise without having to build
it out themselves.”
Lesh is confident his firm will also be able to offer powerful new
tools and approaches that will advance his customers’ work in ways
that will surprise them.
“Discovery companies have limited resources and so have to narrow
their approaches to problems they can tackle,” he says. “But we’ll
be able to offer them the possibility of novel approaches, more
data, powerful new algorithms.
“If they can get access to a larger infrastructure, the power of
what they can do will jump along with that infrastructure.
Chris Brown is a St. Louis-based free-lance writer. |
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