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The Rothberg
Institute for Childhood Diseases Launches First International
Effort to Fight Malaria
PRNewswire
Computational efforts focused on making medicines
to prevent leading cause of death and morbidity in the developing world
The Rothberg
Institute for Childhood Diseases (TRI), a non-profit
research institute devoted to discovering medicines
for orphan childhood diseases such as Tuberous Sclerosis
Complex (TSC), today announced the release of the
first Malaria target to an international community
of more than 54,000 users from 93 countries currently
running the Drug Design and Optimization Laboratory
software (D2OL). "While TRI focuses all of its
laboratory efforts on making therapeutics to cure
TSC, we see strong synergy in expanding our computational
resources to support efforts directed towards emerging
pathogens, bio-terrorism threats, and 3rd World diseases.
This Malaria target was selected to help us test our
methods while providing valuable results for the development
of medicines against the parasite causing this devastating
disease," stated Wolfgang Hinz, Senior Research
Scientist at the Rothberg Institute for Childhood
Diseases. Results from this study can be used to prioritize
the screening of drug-like compounds against the parasite
and will be made freely available to the community
and collaborating laboratories. Increasing resistance
against previously successful therapeutics which targets
the parasite in the blood stage of the life cycle
prompted the scientists at TRI to select Plasmepsin
II, a protease essential for the parasites survival
in the red blood cell. Successful development of inhibitors
of proteases (for example HIV-1 protease) further
supports the choice of target.
Background on Malaria Malaria is
a life-threatening parasitic disease transmitted by
the female Anopheles mosquito, which requires blood
to nurture her eggs. Malaria causes or contributes
to 3 million deaths and up to 500 million acute clinical
cases each year. At least 40% of the world population,
or an estimated 2.5 billion people in over 90 countries
are at risk of becoming infected each year. The main
risk areas are Africa, South East Asia, India and
South America. Risk groups include pregnant women,
refugees, migrant workers, travelers to high risk
areas and children. The majority of deaths are in
children with a mortality rate of 4 children a minute
or 35,000 children a week. Malaria was once widespread,
but it was successfully eliminated or drastically
reduced in 37 countries with temperate climates in
the 1950's (in large part due to the WHO insecticide
spraying program 1956-69). This situation has been
rapidly reversing, especially over the last decade.
This reversing trend can be attributed to the cost
of sustaining programs, loss of motivation in the
face of a seemingly declining threat, the development
of insecticide resistance and resistance against existing
treatments. Malaria parasites are developing unacceptable
levels of resistance to one therapeutic after another
and many insecticides are no longer useful against
mosquitoes transmitting the disease. Years of vaccine
research have produced few hopeful candidates and
although scientists are redoubling the search, an
effective vaccine may be years away.
Background on TSC Tuberous sclerosis
complex (TSC) is a genetic disorder characterized
by the presence of benign tumors, known as hamartomas,
which occur in many tissues and organs including the
brain, eyes, kidney, heart, lungs and skin. Hamartomas
are lumps of disorganized, but differentiated, cells,
which in the case of TSC rarely progress to malignancy.
During the first few years, the severity of TSC can
range from mild skin abnormalities to severe epilepsy,
mental retardation, autism, or attention deficit-hyperactivity
disorder. Three common and life threatening manifestations
of the disease are renal Angiomyolypomas (AMLs), Lymphangioleiomyomatosis
(LAM), and Subependymal Giant Cell Astrocytomas (SEGAs).
We are therefore focusing our drug discovery efforts
towards identifying compounds to treat these specific
lesions. In recent years significant advances in the
understanding of the underlying cause of TSC has been
made. In particular the mutable genes (TSC1 and TSC2)
responsible for the condition were identified and
the role of their respective gene products (harmatin
and tuberin) explored. The CommunityTSC (also utilizing
the D2OL Software) project uses TSC-relevant proteins
identified by sponsored collaborators at Harvard,
Yale, and Fox Chase Cancer Center as therapeutic targets
for computational screening. The targets are screened
against all commercially available drug-like chemical
entities (an estimated 2.5 million potential therapeutics)
to prioritize the compounds to be tested in the laboratory
both at TRI and collaborating academic institutions
worldwide. To date, five targets have been identified
and are currently screened by a user-community in
excess of 18,000 members.
About D2OL D2OL is based on Sengent's
CommunityOS(TM), a grid computing program that harnesses
idle time on volunteer computers from the online community
to create a "supercomputer." This system
is capable of using chemical docking algorithms and
statistical models to rapidly test potential medicines
against any potential target with a known crystal
structure. The Drug Design and Optimization Laboratory
was established in November of 2001 to expedite and
lower the cost of identifying therapeutics capable
of addressing general health issues. The software
was first applied to targets of potential bio-warfare/terrorism
agents such as Anthrax and Smallpox. With the potential
threat posed by emerging Pathogens such as SARS, the
use of D2OL was expanded specifically to protein targets
of the SARS Virus in May of 2003. TRI first applied
D2OL to find a cure for TSC in April of 2002.
About the Rothberg Institute for
Childhood Diseases The Rothberg Institute for Childhood
Diseases is a private, non-profit research institution
dedicated to discovering and developing therapeutics
capable of treating the clinical manifestations of
Tuberous Sclerosis complex (TSC) and other orphan
childhood diseases. TSC is a genetic disorder that
causes benign tumors to form in many different organs,
primarily in the brain, eyes, heart, kidney, skin
and lungs. The Rothberg Institute operates at the
intersection of modern biology, chemistry and computer
science by leveraging technologies including chemical
genomics and grid computing to accelerate its medicine
discovery efforts. Furthermore, the Rothberg Institute
collaborates with academic laboratories at Yale, Harvard
and the Fox Chase Cancer Institute through the Rothberg
Award for Courage in Research administered by the
TS-Alliance. The Rothberg Institute is located in
Guilford; CT. Additional information is available
at http://www.childhooddiseases.org. The latest Version
of D2OL used in the fight against TSC is available
at: http://www.childhooddiseases.org The latest Version
of D2OL used in the fight against emerging pathogens
such as Malaria and SARS and potential bio-weapons
such as anthrax and smallpox is available at: http://www.d2ol.com
.
SOURCE The Rothberg Institute
for Childhood Diseases
Janet E. Verney, Director of Operations
The Rothberg Institute for Childhood Diseases
+1-203-458-7100, fax, +1-203-458-2514
http://www.childhooddiseases.org
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