International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 355-368 http://medscipublisher.com/index.php/ijmms 362 gene therapy approach targeting other neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), also hold potential for informing AD treatment strategies (Fang et al., 2022). 7.2 Pharmacogenomics in dementia treatment Pharmacogenomics, which examines the influence of genetic variations on drug response, plays an increasingly critical role in dementia treatment. Variants in genes such as APOE, CYP2D6, and BCHE affect the metabolism and efficacy of antidementia therapies (Prendecki et al., 2020). For example, the APOE E4 allele not only elevates AD risk but also influences therapeutic response. Identifying these genetic differences enables the personalization of pharmacological interventions, potentially improving therapeutic outcomes. Current pharmacogenomic research aims to pinpoint genetic markers predictive of drug efficacy and adverse reactions, advancing more tailored and effective treatment strategies (Freudenberg-Hua et al., 2018; Prendecki et al., 2020) 7.3 CRISPR and other gene-editing technologies CRISPR and other gene-editing technologies are transforming genetic research and therapeutic approaches, with CRISPR/Cas9 demonstrating considerable promise in AD management by enabling precise correction of pathogenic genetic mutations (Uddin et al., 2020; Bhardwaj et al., 2021). This technology has facilitated the development of empirical AD models, essential for advancing the understanding of disease mechanisms and evaluating new therapeutic strategies. However, CRISPR/Cas9 also presents challenges, including off-target effects and the need for effective delivery systems. To address these issues, researchers are investigating various delivery methods, such as non-viral vectors, to improve the safety and efficiency of CRISPR-based therapies (Hanafy et al., 2020; Uddin et al., 2020). In addition to CRISPR, other gene-editing approaches, including antisense oligonucleotides (ASOs) and RNA interference (RNAi), are under investigation for their potential to target and degrade aberrant mRNA or inhibit the expression of mutant proteins linked to neurodegenerative disorders (Ghaffari et al., 2020; Fang et al., 2022). The convergence of targeted gene therapy, pharmacogenomics, and cutting-edge gene-editing technologies offers substantial potential for developing effective treatments for dementia. Continued innovation and research are essential for addressing current limitations and translating these approaches into clinical applications. 8 Therapeutic Implications of Genetic Research 8.1 Targeted therapies based on genetic findings Recent breakthroughs in genetic research have substantially deepened our understanding of the molecular mechanisms underlying dementia, especially AD. Mutations in genes such as APP, PSEN1, and PSEN2 are established causes of EOAD, while the APOE4 allele is recognized as a significant risk factor for LOAD (Freudenberg-Hua et al., 2018). GWAS uncovered numerous genetic loci linked to AD, including novel risk loci such as IQCK, ACE, ADAM10, ADAMTS1, and WWOX (Heart et al., 2019; Kunkle et al., 2019). These findings have paved the way for the development of targeted therapies aimed at specific genetic alterations. For example, therapeutic strategies focused on the APOE4 allele—such as modulating APOE expression, enhancing its lipidation, or inhibiting its interaction with amyloid-β—have shown promise in preclinical studies (Serrano‐Pozo et al., 2021). Moreover, the identification of pathways related to APP metabolism, tau protein interactions, and immune response offers additional therapeutic targets (Heart et al., 2019; Kunkle et al., 2019). 8.2 Potential for personalized medicine in dementia care The integration of genetic findings into clinical practice holds great potential for personalized medicine in dementia care. By leveraging genetic information, it is possible to predict individual disease risk, understand disease etiology, and tailor treatment strategies to the genetic profile of each patient (Freudenberg-Hua et al., 2018; Hausman-Cohen et al., 2022). For example, individuals carrying the APOE4 allele can be identified as high-risk and may benefit from early intervention and preventive measures (Freudenberg-Hua et al., 2018; Galluzzi et al., 2022). Personalized therapeutic approaches that combine genetic, environmental, and lifestyle risk factors are being explored to improve outcomes for patients with cognitive decline (Eid et al., 2019; Hausman-Cohen et al., 2022).
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