Spanish scientists have found the “key” to Parkinson’s disease in an anti-cancer drug

Pharmaceutical laboratories are increasingly investing in research into the use of a particular drug in other uses for which it is approved.

This may be due to the fact that its repeated use has not been properly studied or due to the fact that drugs entering the body, in addition to performing their therapeutic function, are biochemically transformed by a metabolic mechanism, a process that facilitates their elimination.

This biotransformation leads to the gradual disappearance of the drug, which is converted into its metabolites. They, in turn, can reach high concentrations in the body and also exhibit biological activity that may differ from the activity of the original drug.

That is, the metabolites and the drug coexist in the body and can produce effects that are different from those achieved by using the individual molecules.

This is the case with rucaparib, a drug used in chemotherapy for ovarian cancer, breast cancer and, more recently, prostate cancer, and its metabolite, the M324 molecule.

Well, according to the Supreme Council of Scientific Research (CSIC), a study carried out by researchers Albert A. Antolin from the Oncobell program of the Bellvitge Institute of Biomedical Research (IDIBELL) and ProCure of the Catalan Institute of Oncology (ICO), and Amadeu Llebaria from the Institute of Advanced Chemistry of Catalonia (IQAC -CSIC) showed that rucaparib and its main metabolite M324 exhibit different activities, which opens up new possibilities for the treatment of Parkinson’s disease.

The work, published in the journal Cell Chemical Biology, analyzed rucaparib and M324, allowing a computational prediction of the metabolite’s activity to be made.

The article describes the synthesis of M324 and its biological analysis, demonstrating that the drug (which is part of a group of drugs intended to treat several types of cancer that demonstrate changes in DNA repair. In particular, they are inhibitors of the enzyme PARP1, which is involved specifically in the process of correcting mutations in genetic material) and its metabolite have differential activity and act synergistically in some prostate cancer cell lines.

AND, Surprisingly, M324 reduced the accumulation of the protein α-synuclein (an important component of Lewy bodies) in neurons obtained from patients with Parkinson’s disease. a neurodegenerative disease characterized by a movement disorder in which neurons do not produce enough of the neurotransmitter dopamine.

In particular, the synergy demonstrated between rucaparib and M324 in prostate cancer cell lines may have implications for advanced clinical trials of this cancer type.

On the other hand, the fact that M324 is able to reduce the abnormal accumulation of alpha-synuclein in neurons derived from stem cells of a patient with Parkinson’s disease highlights the therapeutic potential of this metabolite and its possible pharmacological application for the treatment of this disease. at least 150,000 people were affected in Spain.

It is the second most common neurodegenerative disorder after Alzheimer’s disease, and the number of sufferers is projected to double by 2040 and triple by 2050 due to increased life expectancy and, among other things, advances in therapeutics and increased exposure to toxins.

The researchers used computational and experimental methods to comprehensively characterize the pharmacology of the M324 molecule for the first time.

The findings may have implications for the clinical treatment of rucaparib and, in turn, open new avenues for drug discovery.

To summarize, the study indicates a new conceptual view in pharmacology: viewing drug metabolism not as an unwanted process that destroys and removes the therapeutic molecule from the body, but rather as potential benefits from a therapeutic point of view.

Indeed, the work highlights the importance of characterizing the activity of drug metabolites for a comprehensive understanding of their clinical response and its application in precision medicine.