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By Jennifer Swieck

Jennifer SwieckOver the past few decades the amount of protein therapeutics to enter the market has grown substantially. With the advent of new technologies brings new problems, the biggest of which is the immunogenicity of these drugs. The immune response toward therapeutic proteins can compromise both the safety and the efficacy of treatment in patients. Methods to overcome the immune response are crucial in order to improve treatment options for patients.

A strategy to overcome immune responses towards therapeutics is being developed in the lab of Sathy Balu-Iyer, Ph.D., at the University of Buffalo. This strategy utilizes the immune regulatory properties of phosphatidylserine (PS), a naturally occurring component of cell membrane in our bodies. In this approach the drug is associated with a liposome composed of PS. Administering the drug in the presence of these PS containing liposomes influences the body to accept the compound, instead of mounting an immune response. We have shown that giving factor VIII (FVIII), a treatment for hemophilia A, in the presence of PS can reduce the immune response towards FVIII and can continue to suppress the immune response toward FVIII even after treatment with PS has ended. This work received an AAPS Biotechnology Innovation Award in 2012.

The work presented at the 2014 AAPS National Biotechnology Conference will showcase the expansion of this approach to another protein therapeutic: recombinant human acid alpha glucosidase (rhGAA). Currently, this enzyme is given as a drug to treat Pompe disease, a rare inherited genetic condition that results in a less functional or nonfunctional version of this enzyme. Treatment with products currently on the market is severely hindered by the fact that a majority of patients mount an immune response again the administered drug. Once therapy fails due to the formation of an immune response, there are no alternative treatment options for patients.

We were able to show that administering rhGAA in the presence of PS liposomes can decrease the immune response and can also induce tolerance towards future injections of rhGAA in a mouse model of Pompe disease. The success of demonstrating the ability of PS to reduce unwanted immune responses for another therapeutic protein drug suggests a promising treatment option. Further investigation into this approach is ongoing.

This research will be presented at the Bayside Pavilion today from 10:00 am–2:00 pm PST. For more information, the abstract, no. T2001, can be found on the NBC  app online or via your mobile device.

Jennifer Swieck is pursuing a Ph.D. in pharmaceutical sciences at the University at Buffalo in Buffalo, NY, under the guidance of Sathy V. Balu-Iyer, Ph.D.