Current Issue : October-December Volume : 2026 Issue Number : 4 Articles : 5 Articles
Background/Objectives: To assess the knowledge, attitudes, and practices of ophthalmologists in Saudi Arabia towards genomic medicine and genetic testing, in light of the growing significance of genomics in ophthalmology and the national transition towards precision medicine. Methods: A cross-sectional, questionnaire-based survey was conducted among ophthalmologists, including consultants, specialists, fellows, and residents, across Saudi Arabia. The questionnaire included four domains: demographics, knowledge of genomic principles and gene therapy, self-rated confidence in genetic tasks (scored 1–10), and attitudes toward genetic testing. Data were analyzed using descriptive and inferential statistics, with subgroup comparisons performed using chi-square tests and t-tests/ANOVA. Results: A total of 115 ophthalmologists participated (46% male, 54% female; mean age 34 years; mean post-board experience 4 years). Most were consultants (40%) and practiced in Riyadh (52%). Knowledge was variable: 92% correctly identified human chromosome count, and 99% recognized autosomal recessive inheritance, but only 9% answered DNA base-pairing correctly, and 54% recognized mitochondrial inheritance. Confidence was highest for referral to specialists (mean 7.3/10) and lowest for test selection and counseling (4.7/10). The internet was the primary knowledge source among our sample (65%). The majority of individuals had positive attitudes towards genomic medicine: 90% believed testing was beneficial, 89% considered it enhanced health outcomes, and 89% indicated they would undergo testing themselves. On the other hand, 77% indicated difficulty in access, 91% strongly concurred on the significance of privacy and confidentiality, and more than half expressed concerns regarding misuse and bias. Conclusions: Ophthalmologists in Saudi Arabia acknowledge the importance of genetics. Yet, there are substantial gaps in knowledge and familiarity with genomic medicine and genetic testing. To overcome these challenges, it is essential to integrate genetics into ophthalmology curricula....
Background/Objectives: Breast cancer (BC) is a highly prevalent neoplasm worldwide. Despite the wide range of therapeutic options currently available, it remains the leading cause of cancer-related mortality among women. Capecitabine, a prodrug of 5-fluorouracil (5-FU), is widely used in the treatment of advanced BC. However, despite its efficacy, capecitabine exhibits considerable interindividual variability in therapeutic response. This study aimed to evaluate the effect of single-nucleotide polymorphisms (SNPs) in genes involved in capecitabine bioactivation on progression-free survival (PFS) in patients with BC. Methods: An ambispective cohort study was conducted. Four relevant SNPs in the CES1, CDA, and TYMP genes were analyzed in 85 Caucasian patients with BC using real-time polymerase chain reaction (PCR) with TaqMan® probes. Results: A significant association was observed between shorter PFS and the GA genotype of the CES1 rs71647871 SNP (p = 0.010; HR = 7.46; 95% CI = 1.24–122.52), as well as with the TT genotype of the CDA rs602950 SNP (p = 0.009; HR = 3.50; 95% CI = 1.36–9.03). Conclusions: These findings suggest that CES1 rs71647871 and CDA rs602950 may serve as predictive biomarkers of capecitabine effectiveness in patients with BC. Further studies involving larger cohorts are needed to validate these findings and generate additional evidence to support their potential implementation in clinical practice....
Glutaric aciduria type 1 (GA1) is a rare neurometabolic disorder caused by glutaryl-CoA dehydrogenase (GCDH) deficiency, leading to the accumulation of neurotoxic metabolites that can cause both acute encephalopathic crises and progressive, insidious brain injury. Current management primarily relies on a protein-restricted diet, which remains therapeutically insufficient and burdensome for patients, highlighting the need for disease-modifying therapies. In this study, we established a novel GA1 mouse model using CRISPR/Cas9 technology and evaluated the preclinical efficacy of systemic recombinant adeno-associated virus (rAAV)-mediated gene therapy. Under standard dietary conditions without highlysine challenge, our GA1 model exhibited sustained cerebral and hepatic glutaric acid (GA) accumulation and distinct chronic vacuolation in the hippocampus and cerebellum, mirroring the insidious-onset GA1 phenotype. Five-week-old mice received a single intravenous injection of rAAV-hGCDH using either rAAV2/8 or rAAV2/9 serotypes. Systemic rAAVmediated gene therapy significantly reduced GA accumulation and attenuated chronic neuropathological changes in this GA1 mouse model for both serotypes. Our findings support the hypothesis that peripheral metabolic correction may play an important role in preventing the chronic neuropathological changes associated with GCDH deficiency. However, further investigation using tissue-specific expression systems is required to definitively delineate the relative contributions of hepatic versus central GCDH restoration to the observed neuroprotection....
Optogenetic gene therapy-based treatment offers a unique approach to bypass dysfunctional or degenerated photoreceptors in retinal degenerative disorders. Ambient lightactivatable multi-characteristic opsin (MCO) targeted to bipolar cells of the retina has demonstrated partial vision restoration in animal models of retinitis pigmentosa (RP). Here, we describe the potential therapeutic efficacy of intravitreally delivered AAV-carried MCO-010 in a mouse model of Stargardt disease. MCO-010 treatment led to significantly improved behavioral outcomes in the visually guided radial arm water maze. Furthermore, longitudinal optical coherence tomographic imaging showed that the MCO-010 treatment led to no notable change in the retina thickness. Furthermore, the MCO-010-treated mice exhibited higher electrophysiological responses compared to the control group. Together, these findings demonstrate potential vision-restoring and disease-modifying aspects of ambient light-activatable intravitreal MCO-010 therapy....
Duchenne muscular dystrophy (DMD) is a fatal rare disease caused by dystrophin deficiency, with no effective clinical treatments available to date. Using mdx mice as a model, this study investigated the therapeutic efficacy and interaction of mini utrophin (a truncated utrophin) and Yes-associated protein (YAP) delivered via recombinant adeno-associated virus (rAAV). Results showed that mini utrophin was efficiently expressed in mdx mouse skeletal muscle, significantly increased phosphorylated YAP (p-YAP) levels, restored the expression of dystrophin–glycoprotein complex (DGC) components (α/γ-sarcoglycans), reduced serum creatine kinase (CK) leakage, alleviated pathological damages such as central nucleation and inflammatory infiltration, and comprehensively improved grip strength, treadmill endurance, and pole climbing ability in mice. However, the co-overexpression of YAP completely antagonized these therapeutic effects, resulting in no improvement in pathological phenotypes or motor function of mdx mice. This study confirms that mini utrophin can effectively reverse DMD-related phenotypes, while excessive YAP activation abrogates its therapeutic efficacy, suggesting that precise regulation of YAP activity is required in DMD treatment and providing experimental basis for optimizing gene therapy strategies....
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