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.