Abstract ID: 2504
Abstract Title: Final results of Phase I and pharmacokinetic trial of SJG-136 administered on a daily x 3 schedule.
Session Type: Oral Presentation
Role: Presenter Igor Puzanov
Date:
Monday, June 02, 2008
Time: 8:00AM - 11:00AM
Presentation Time: 8:30AM - 8:45AM
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Centanamycin has dual activity against malaria
by Scott Baltic
Last Updated: 2008-03-17 17:13:43 -0400 (Reuters Health)
NEW YORK (Reuters Health) - By damaging the DNA of the Plasmodium parasite that causes malaria, centanamycin can
both rapidly reduce levels of parasitemia during blood-stage infections in mice and arrest the development of the
parasites in the mosquito vector, blocking transmission, according to the findings of a recent study.
Dr. Stephanie Yanow of the Provincial Laboratory for Public Health in Edmonton, Alberta, Canada and colleagues
conducted in vitro and in vivo studies with centanamycin, one of a new generation of adenine/thymine-specific alkylating
agents, exploring the drug's potential as "a novel biochemical strategy to block malaria transmission."
To this end, the multinational group of researchers used three strains of Plasmodium, according to the report published in
the February 15th issue of the Journal of Infectious Diseases.
One experiment showed that centanamycin has "potent cytotoxic effects" on both chloroquine-sensitive and
chloroquine-resistant strains of P. falciparum in vitro.
In another trial, in mice infected with an avirulent strain of P. chabaudi adami, parasitemia became subpatent after a
single injection of centanamycin (15 mg/kg) 4 days after infection.
In another experiment, in mice with established P. chabaudi adami infections, a single injection of centanamycin 5 mg/kg
reduced parasitemia by 83%, compared with that in control mice (p = 0.006), in 24 hours.
Tested against a virulent strain of P. chabaudi adami, a single injection of centanamycin 15 mg/kg cleared the initial
infection, with parasitemia in the treated mice remaining subpatent for at least 6 days. In comparison, control mice all
rapidly developed malarial infection and had either died or been euthanized by day 10 after infection.
A further experiment in which drug-treated mice were rechallenged with a second P. chabaudi adami strain suggests that
"a reduction of parasitemia after antimalarial treatment enables mice to acquire immunity."
Finally, in an experiment in which mosquitoes fed on centanamycin-treated mice, the average number of P. berghei
oocysts was reduced by 83% versus control mice (p = 0.012). In addition, many of the oocysts were misshapen or
abnormally small, and further study indicated that almost none of the oocysts developed to the sporozoite stage.
Centanamycin "could represent a valuable new addition to combination therapies for treating malaria," Dr. Yanow told
Reuters Health. This type of drug "could help treat the person infected with the disease and also reduce the overall
burden of malaria within the larger community. This could significantly reduce the number of deaths from malaria each
year, which now stands at over 1 million."
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Spirogen Ltd. is a pharmaceutical company pioneering the discovery and development of a unique class of low molecular weight, sequence-selective, DNA-interactive drugs designed to treat gene-mediated diseases. Spirogen has an extensive patent portfolio, including a number of granted patents, relating to its core technology. A number of the cases cover active PBD compounds, and their uses in medicine. The company was founded in March 2000. Spirogen has 10 employees split between laboratory and office facilities at new custom designed facilities at The School of Pharmacy (University of London) and the Cancer Institute (University College London).
www.spirogen.com
Leading in DNA Targeted Therapeutics