Researchers produce artificial antibody capable of blocking prions in the laboratory

Prion diseases affect the brain, causing neurodegenerative problems that always lead to death. They attracted attention in the late 1990s due to the "Mad Cow" scare. Today they remain incurable and poorly understood at the molecular level. Although the Mad Cow disease is not a threat anymore due to veterinary control, human prion diseases (hereditary and sporadic forms) kill about 400 people per year in Europe.

The group of Luca Varani, at the Institute for Research in Biomedicine (IRB, affiliated to USI Università della Svizzera italiana, Switzerland) has produced an artificial antibody capable to block prions in the laboratory, even when administered when signs of infectious neurodegeneration are already apparent in the cellular models. The study, published in the scientific journal PLOS Pathogens and performed in collaboration with the University of Zurich, sheds new light on the mechanism responsible for prion neurotoxicity and paves the way to new therapeutic approaches against prions and other neurodegenerative diseases.

Prion diseases are caused by a protein that, due to unknown molecular causes, can transform into an infectious and toxic agent: the prion. These diseases can have sporadic or hereditary origin, due to DNA mutations. In the Mad Cow disease, today almost totally eradicated, the human pathology is caused by ingestion of prions present in infectious animals. Prion diseases are rare, it is therefore important that research, performed by universities and no-profit institutions, is supported by government agencies and private entities.

The IRB researchers used a mix of computational simulations and laboratory experiments to develop an antibody that solves both above problems starting from an extravagant but effective idea. They took a toxic antibody that can trigger prion diseases (the Ugly) and they fused it with an antibody that is not toxic but cannot protect from prion (the Good), obtaining an artificial "double" antibody ("bispecific" in scientific terms) that can cure prion disease in the laboratory even if administered when signs of neurodegeneration are already apparent (the neuroprotective).

In the last few years, researchers from all over the world have put great hope in antibody-based therapies. Antibodies, natural molecules of the immune system, developed so far can protect from prion in laboratory tests only if administered before the infectious agent: the prion itself. This complicates their therapeutic use, since prion diseases are diagnosed only when neurodegeneration is already apparent, and at this stage these antibodies would be ineffective. Even worse, some antibodies can trigger neurotoxic reactions even in the absence of prion infection.