Neurodegenerative diseases such as Alzheimer's disease or dementia often coexist with other mental illnesses such as anxiety and depression, which implies the daily consumption of a multitude of drugs for different treatments. A patient with dementia may consume more than a dozen drugs every day. As the number of drugs consumed increases, the risk of drug interactions or adverse reactions increases considerably. By implementing pharmacogenetic procedures, it is possible to reduce these interactions and reactions in number and severity.
The importance of genes in drug response
The body's response to drugs is regulated by different groups of genes:
- Pathogenic genes associated with the primary cause of the disease.
- Mechanistic genes, related to the mechanisms of action of each drug.
- Metabolic genes, responsible for drug metabolism in liver, intestine and other tissues.
- Transporter genes, which encode transport proteins to regulate the flow of drugs in and out of target organs.
- Pleiotropic genes, involved in multiple active metabolomic pathways when drugs are consumed.
The accumulation of defective variants in these genes (>30 genes per patient in more than 50% of cases) influences the therapeutic response to antidementia, antidepressant and anxiolytic drugs in polyvalent regimens. The genes that most influence the therapeutic response to depression and anxiety in Alzheimer's disease are: APOE, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, CYP3A5, CYP4F2, COMT, MAOB, CHAT, GSTP1, NAT2, SLC30A8, SLCO1B1, ADRA2A, ADRB2, BCHE, GABRA1, HMGCR, HTR2C, IFNL3, NBEA, UGT1A1, ABCB1, ABCC2, ABCG2, SLC6A2, SLC6A3, SLC6A4, MTHFR and OPRM1.
Benefits of multipurpose treatments
A study in more than 2,500 Spanish patients with dementia, who also suffered the consequences of concomitant depression and anxiety, treated with a multipurpose therapeutic strategy, shows that, while cognitive improvement is very modest during the first year of treatment, the antidepressant and anxiolytic response is excellent in more than 80% of cases. In general, women are more prone to depression and anxiety than men, but the response to multifactorial treatment is similar in both sexes.
The Euroespes team led by Dr. Ramón Cacabelos has been researching for years in the field of PharmacoGenetics with more than 2,000 publications and the creation of the first World Guide to PharmacoGenetics and the development of the Digital Platform of Genomic Medicine Mylogy.
Cacabelos R, Carril JC , Corzo L, Pego R, Cacabelos N, Alcaraz M, Muñiz A, Martínez-Iglesias O, Naidoo V. Pharmacogenetics of anxiety and depression in Alzheimer's disease. Pharmacogenomics 10.2217/pgs-2022-0137, 2023.