Alpha-defensins (HNPs) Effectively Inhibit Anthrax-related Toxemia
Medizin : Therapeutika
Scientists from the Max Planck Institute for Infection Biology in Berlin revealed that human neutrophil alpha-defensins (HNP-1/-2/-3) are potent inhibitors of LF. They showed that human neutrophil protein HNP-1 protected murine macrophages from B. anthracis-induced cytotoxicity in vitro. Even more encouraging, they also found that in vivo treatment with HNPs protected mice against the fatal consequences of anthrax LeTx (3). Alpha-defensins are natural peptides of human origin. Hence, they have a higher potential to be more useful than any known synthetic anthrax therapeutic.
Development and Commercialization Opportunities
A large scale solid-phase synthesis manufacturing protocol has been described for HNPs (4). Moreover, in December 2006, novel legislation relating to biodefense research and development came into effect in the US. Biotech companies can now receive funds upfront, and reimbursement of costs is no longer dependent on previous licensure of a product by the FDA.
Therefore HNPs provide a perfect opportunity from a scientific and technical as well as from an economic perspective to launch a novel therapeutic, possibly in combination with antibiotics or vaccines to effectively inhibit anthrax-related toxemia.
European priority application filed in July 2004, via PCT extended to EP, US and CA.
- “The worldwide emergence of plasmid-mediated quinolone resistance”, Lancet Infect Dis. 2006 6: 629-40.
- Nature 2007, Vol. 445: 12.
- “Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences”, Proc Natl Acad Sci USA 2005 102: 4830-35.
- “Large scale synthesis and functional elements for the antimicrobial activity of defensins”, Biochem J 2000 347:633-641.
Mechanism of action - Taken from nature:
A neutrophile granulocyte phagocytes anthrax bacteria, thereby exposing them to alpha defensins stored in its granuloma that can neutralize B. anthracis's most deadly weapon: lethal toxin.
It seems that in the lung neutrophile granulocytes are present in amounts too low to control B. anthracis infection. However, mice control anthrax infection after administration of alpha-defensins.
- Ref.-No.: 0305-3252-LI (325,4 KiB)
Dr. Dieter Link
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