2023-07-31 14:56:48
From Italian research an unprecedented hope for a cure against prions, infectious proteins responsible for deadly neurodegenerative diseases such as Creutzfeldt-Jakob disease or its variant considered the human version of mad cow disease. The discovery, published in ‘iScience’, bears the signature of an Italian team coordinated by the Mario Negri Irccs Institute for Pharmacological Research. The study, conducted in collaboration with the Irccs San Raffaele hospital in Milan and the University of Insubria, identified in in vitro experimental models “a molecule that belongs to the class of porphyrins and exploits a dual mechanism of action, never before described – explain the authors – which makes it active against all types of prions and prevents them from becoming resistant to drugs”. The work was supported by the Telethon Foundation, the Ministry of Health, the CJD Foundation and the Italian Prion Encephalopathies Association (Aienp).
Prion diseases, or transmissible spongiform encephalopathies – recalls a joint note from Mario Negri, San Raffaele and the University of Insubria – are rare degenerative diseases of the central nervous system that affect humans and other mammals. They are caused by prions, altered forms of the prion protein normally found on the surface of nerve cells. The prion protein can become a prion for several reasons: spontaneously, for no known reason; for genetic mutations; following an infection with prions from another organism, such as in the case of transmission of mad cow disease to humans. The accumulation of prions in brain cells causes the formation of microscopic holes that make the brain tissue look like a sponge. After the first symptoms appear, the disease progresses rapidly, leading to death.
“Unfortunately, there is no cure today,” underlines Roberto Chiesa, head of the Neurobiology Laboratory of prions at the Mario Negri Institute. “One of the reasons – specifies the expert – is linked to the fact that, as they replicate, prions mutate and make it difficult to identify therapies capable of eradicating them. During the study on experimental models in vitro, we studied the effect of some molecules on the ability of prions to replicate and we have identified one that performs a double action: on the one hand it prevents the prion protein from transforming into a prion, on the other it induces its elimination from the surface of nerve cells”.
“This discovery is very important – assures Giovanna Musco, head of the Biomolecular Nuclear Magnetic Resonance Laboratory of the Irccs San Raffaele in Milan – because it highlights a completely new mechanism that blocks the replication of prions and prevents them from mutating, consequently developing a resistance to possible therapies. We intend to exploit this evidence to be able to formulate a new class of drugs to treat these terrible diseases”.
“The next objective in this direction – anticipates Enrico Caruso of the Department of Biotechnology and Life Sciences of the University of Insubria – is to study how to chemically modify the identified molecule, a porphyrin, which due to its characteristics cannot currently be used as a drug, or identify molecules that act with the same mechanism of action, but have better pharmacological properties”.
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