Researchers from several Catalan scientific centers have found in an anti-cancer drug, Rucaparib, the potential in the body for Parkinson’s treatments due to the biochemical transformations that these products leave in the body.
This is explained in a study published in the journal Cell Chemical Biology by researchers Albert A. Antolin, from the Oncobell program of the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona and ProCure of the Catalan Institute of Oncology (ICO), and Amadeu Llebaria, from the Institute of Advanced Chemistry of Catalonia (IQAC-CSIC).
Scientists begin by explaining that once they enter the body, drugs, apart from performing their therapeutic function, are biochemically transformed by the action of the metabolic machinery, a process that facilitates their expulsion.
This biotransformation results in a gradual disappearance of the drug, which is converted into its metabolites and these, in turn, can reach high concentrations in the body and also show a biological activity that may be different from that of the original drug. .
“That is, the metabolites and the drug coexist in the body, and can cause effects different from those obtained with the individual molecules,” they point out.
That would be the case of Rucaparib, a drug used in chemotherapy for ovarian cancer, breast cancer and, more recently, prostate cancer, and its metabolite, the M324 molecule.
The scientific study has analyzed the relationship between Rucaparib and M324, and it has been shown that the drug and its metabolite have differentiated activities and act synergistically in some prostate cancer cell lines.
Likewise, and this is what they highlight most, “surprisingly, M324 reduces the accumulation of the protein ?-synuclein (an important component of Lewy bodies), in neurons derived from Parkinson’s patients, a neurodegenerative disease characterized by a disorder of movement, and in which neurons do not produce sufficient amounts of the neurotransmitter dopamine.
Likewise, they explain, “the fact that M324 is capable of reducing the abnormal accumulation of ?-synuclein in neurons derived from stem cells of a Parkinson’s patient, highlights the therapeutic potential of this metabolite and its possible pharmacological application for the treatment of this neurodegenerative disease.
The team of researchers point out that beyond the specific case, this discovery points towards a new conceptual perspective in pharmacology: “one that considers drug metabolism not as an undesirable process that degrades and eliminates the therapeutic molecule from the body, but rather as may have potential advantages from a therapeutic point of view.
Therefore, they say, it is important to characterize the activity of drug metabolites that are derived in the body after ingestion “to comprehensively understand their clinical response and apply it in precision medicine.”
