Parasitic diseases are responsible for the death and suffering of millions of individuals in Africa, Asia, and South America. Malaria alone results in nearly one million deaths per year, largely children below the age of 5. "Many of the drugs currently utilized to treat parasitic diseases are decades old, suffer from toxicity and developing parasite resistance," says John Siekierka, professor of chemistry and biochemistry and founding director of Montclair State University's Sokol Institute for Pharmaceutical Life Sciences. "New treatment options are urgently needed."
Siekierka's current research focuses on targeting mechanisms that parasites use to escape destruction by host immune responses. He is studying two parasites: Leishmania, a single-celled organism introduced into humans by the bite of an infected sand fly, and Brugia malayi, a parasitic worm responsible for the disease lymphatic filariasis (elephantiasis) in tropical regions.
"Leishmania infection results in terrible skin lesions and can be fatal if not treated," explains Siekierka, who has been targeting a specific Leishmania protein kinase with synthetic drugs. "Protein kinases are the cell's switching machinery controlling many critical cellular processes. The Leishmania protein kinase under study is absolutely required for the parasite to survive in the host. The goal of this research is to design drugs that prevent this protein kinase from functioning, thereby preventing the parasite from surviving in the host."
With the Brugia malayi parasite, Siekierka, along with his students, identified a protein kinase that the parasite needs to protect itself from stress and immune destruction. "We've been able to target this protein kinase with drugs that block its action in the worm. The end result is the worm cannot respond to the stress of the host immune response and quickly die."
In May 2010, Montclair State University entered into a formal
sponsored research agreement with the Celgene Corporation in Summit, New
Jersey, and Celgene Global Health (CGH). CGH collaborates with partners
around the globe to find solutions for healthcare challenges in the
The agreement allows Siekierka to assess a collection of Celgene propriety kinase inhibitors for activity against novel parasitic protein kinases identified through his research. "This program has advanced to a new level with a greatly expanded scope," Siekierka says. "Novel Celgene inhibitors are being used as lead structures that may become potentially new therapeutics for the treatment of human filarialsis."
Sokol Professor of Chemistry David Rotella will be conducting medicinal chemistry initiatives to enhance the potency, selectivity, and metabolic stability of the Celgene inhibitors identified to date. With more than 20 years experience in the field of medicinal chemistry, Rotella leads a team of chemists designing and synthesizing improved inhibitors that will be evaluated by Siekierka's group. "This exciting endeavor represents an early stage drug discovery program at Montclair State University," Siekierka says.