G Protein Mediated Function as a Target for Malaria Chemotherapy (22096)
Investigators at Northwestern University have identified that beta-blocker drugs are effective inhibitors of malarial infection in vitro and in vivo. Beta blockers are inexpensive, approved to treat cardiac indications, non-toxic, and otherwise well-tolerated in patients. Research and development efforts have yielded a variety of beta blocker compounds, clinical trial data, and extensive data on pharmacodynamic and pharmacokinetic properties of these drugs. This technology offers the opportunity to use a well characterized drug for a new, much needed application and the impetus for the development of new beta-blocker drugs to be tested for their effectiveness in the treatment of malaria.BACKGROUND: Plasmodium falciparum causes the most virulent form of human malaria, a disease that afflicts 200-300 million people and kills over one million children each year. The asexual, blood stages of infection are responsible for all of the symptoms and pathologies of the disease. Thus blocking these stages is expected to be important for controlling acute infection as well as disease pathologies. Malaria is a disease with tremendous morbidity and mortality, due to the lack of new drugs and the emergence of resistance to existing drugs. Plasmodium falciparum causes the most virulent of human malarias. The blood stages of infection are responsible for all of the symptoms and pathologies associated with the disease. Thus development of new drugs against blood stage infection is important to disease control.
Using peptides derived against the C-terminus of Gs proteins, the investigators demonstrated that blockade of Gs signaling resulted in decreased malaria infection in vitro and in vivo. These results led to investigations examining the role that G-protein coupled receptors expressed in red blood cells have in malaria infection and led to the discovery described herein.
ADVANTAGES: Research and development efforts of pharmaceutical companies have yielded a variety of beta blockers, clinical trial data, and extensive data on pharmacodynamic and pharmacokinetic properties of these drugs. Hence their new use as effective treatment of malaria may be accomplished with modest investments. Investigators at Northwestern University have identified that beta-blocker drugs are effective inhibitors of malarial infection in vitro and in vivo. Beta blockers are inexpensive, approved to treat cardiac indications, non-toxic, and otherwise well-tolerated in patients. Research and development efforts have yielded a variety of beta blocker compounds, clinical trial data, and extensive data on pharmacodynamic and pharmacokinetic properties of these drugs. This technology offers the opportunity to use a well characterized drug for a new, much needed application and the impetus for the development of new beta-blocker drugs to be tested for their effectiveness in the treatment of malaria.
BACKGROUND: Plasmodium falciparum causes the most virulent form of human malaria, a disease that afflicts 200-300 million people and kills over one million children each year. The asexual, blood stages of infection are responsible for all of the symptoms and pathologies of the disease. Thus blocking these stages is expected to be important for controlling acute infection as well as disease pathologies. Malaria is a disease with tremendous morbidity and mortality, due to the lack of new drugs and the emergence of resistance to existing drugs. Plasmodium falciparum causes the most virulent of human malarias. The blood stages of infection are responsible for all of the symptoms and pathologies associated with the disease. Thus development of new drugs against blood stage infection is important to disease control.
Using peptides derived against the C-terminus of Gs proteins, the investigators demonstrated that blockade of Gs signaling resulted in decreased malaria infection in vitro and in vivo. These results led to investigations examining the role that G-protein coupled receptors expressed in red blood cells have in malaria infection and led to the discovery described herein.
ADVANTAGES: Research and development efforts of pharmaceutical companies have yielded a variety of beta blockers, clinical trial data, and extensive data on pharmacodynamic and pharmacokinetic properties of these drugs. Hence their new use as effective treatment of malaria may be accomplished with modest investments.
Inventor(s): Travis Harrison, Heidi Hamm, Jon Lomasney and Kasturi Haldar
Type of Offer: Licensing
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