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Jason Thomas Duskey and Barbara Ruozi

Grant Title: Optimization of nanoparticle-mediated brain delivery of a tetracationic porphyrin with potent anti-prion activities

Location: University of Modena and Reggio Emilia, Modena, Italy

Grant Year: 2021



Prion disease affects people worldwide with an annual incidence of about two cases per million population. It is caused by the shift of the naturally occurring prion protein from its normal to its infective form. Unfortunately, treatments for this disease are almost completely based on symptom control and there are no effective clinical treatments to stop or slow the progression of the disease.

A class of molecules known as porphyrins was shown to block the infective protein in cell models. Advancing this research, in a collaboration between our groups at the University of Modena and Reggio Emilia (Modena Italy), the Mario Negri Institute (Milano, Italy), and the San Raffaele Hospital (Milano Italy), we have studied a new porphyrin that can block both the infective and pre-infective form of the protein, making it a potential treatment for those with the disease as well as a potential preventative measure for those at risk of developing the disease. However, the molecule by itself does not enter the brain in sufficient amounts to have its desired effect.

Nanomedicines, particularly nanoparticles made from a non-toxic polymer that is FDA approved, have been used by our lab to transport similar drugs into the brain. Combining our nanoparticles with the new drug molecule showed promising results in cell experiments, but in animal studies the drug seemed to interact with the nanoparticles in an unexpected way that blocked the brain targeting.

Therefore, in this project we will analyze the interaction between the porphyrin and the nanoparticles to discover what is blocking the brain targeting. Once discovered, the nanoparticles will be modified to boost their brain penetration, and the potential therapeutic effects of this improved nanomedicine will be tested in animal models of the disease. By harmonizing the potential of this molecule with the nanomedicine system, we aim to improve brain delivery of this porphyrin and pave the way for more detailed studies in animals, and ultimately for the treatment and inhibition of the infective prion protein, giving new hope to prion disease patients and their families.

About the Researcher:

Jason Thomas Duskey, PhD, and Barbara Ruozi, PhD
University of Modena and Reggio Emilia, Modena, Italy

Dr Jason Thomas Duskey attended Mount Mercy College to earn his B.S. He then studied at the University of Iowa receiving his Ph.D. in brain cancer targeted gene therapy in 2013. He transferred to Basel Switzerland studying polymer-based nanoparticles for the delivery of biological actives before arriving to the University of Modena and Reggio Emilia in 2016 continuing to study targeted nanomedicine delivery systems for brain targeting. Due to these works, he is the recipient of numerous awards and independent research grants spanning 5 languages and more than 8 countries leading to him successfully obtaining Abilitazione Scientifica Nazionale in Italy.

Recipient of:

The Strides for CJD Research Grant

Contributed by: The Families of the CJD Foundation

Funds raised by the annual Strides for CJD run/walk have been applied to research grants awarded since 2016.