Gene and cell therapies have emerged as innovative therapeutic strategies, offering a new paradigm in the treatment of prostate cancer. This review explores the current state of gene and cell therapies, including their mechanisms, applications, and the challenges faced in clinical translation. The article selection was based on the 2020 preferred reporting items for systematic reviews and meta-analyses (PRISMA). Eighty-four (84) articles (published in English between 2018 and 2024) from standard electronic databases were extracted and reviewed. Key therapeutic approaches such as viral vector-mediated delivery, CRISPR-Cas9 gene editing, suicide genes, cell-based therapies like CAR T cell therapy, and dendritic cell vaccines that target specific tumor antigens were reviewed. These therapies promise to enhance therapeutic efficacy with few challenges, like off-target effects, limited delivery efficiency, and immune-related toxicities associated with delivery. Advances in CAR T cells, nanoparticle-based gene delivery systems, and epigenetic modulation are potential solutions to these challenges. Combination therapies involving gene and cell therapies with immunotherapies and oncolytic viruses hold the potential for synergistic treatment effects. Certain critical regulatory, ethical, and accessibility issues must be addressed to ensure the safe and equitable deployment of these therapies. Continued research and innovation in gene and cell therapies and streamlined regulatory pathways will be crucial for realizing their full potential in treating prostate cancer. Overcoming these challenges and fears confronting gene and cell therapies worldwide might facilitate a stream of personalized medicine in prostate oncology.

Aim: Inherited Bone Marrow Failure Syndromes (IBMFS) are increasingly diagnosed in both pediatrics and adults presenting with cytopenias, myelodysplastic syndrome, and acute leukemia due to increased awareness among providers. Given the multi-organ involvement in IBMFS, the referrals for genetic testing have extended to individuals with pulmonary fibrosis, liver cirrhosis, and concerns for cancer predisposition in other solid tumors. The purpose of this study is to highlight the real-world data of genetic testing in an Inherited Bone Marrow Failure clinic and the challenges faced.

Method: Patients who were referred to the Medical Genetics and Genomics Outpatient Clinic for evaluation of a suspected underlying IBMFS at the University of Iowa from January 2023 to September 2024 were enrolled in this study. Clinical phenotypes, reasons for referrals, and genetic testing results were recorded and analyzed.

Result: A total of 16 individuals from 15 families were enrolled in this study during this period. Clinical-grade genetic testing yielded a diagnosis in 50% of the patients, with a predominance of patients diagnosed with a telomere biology disorder.

Conclusion: Early diagnosis of an underlying IBMFS is important to reduce mortality and morbidity. Genomic testing is crucial to provide an accurate diagnosis and appropriate management, including donor selection when hematopoietic stem cell transplant is a treatment option.

Aim: Osteoporosis (OP) is the most common of the musculoskeletal disorders, with decreased bone mineral density (BMD) being the main manifestation and exacerbating fracture susceptibility. OP was once thought to be an inevitable consequence of aging. We conducted a bi-directional Mendelian randomization (MR) for epigenetic age acceleration (EAA) and osteoporosis to accurately assess the interaction between aging and osteoporosis.

Methods: This study collected data from genome-wide association studies of EAA and OP and assessed significant genetic variables. Bi-directional MR analyses were performed using random-effects inverse-variance weighting as the primary method, and the interaction of epigenetic age acceleration with OP was assessed using other MRI methods and multiple sensitivity analyses.

Results: Inverse-variance weighted (IVW) results suggest that GrimAge acceleration accelerates bone loss in total body bone mineral density [odds ratio (OR) = 1.035, 95% confidence interval (95%CI) = (1.003, 1.069), P = 0.033]. The effect of BMD on EAA was investigated, and a causal relationship was found between forearm bone mineral density and GrimAge acceleration [OR = 0.682, (95%CI) = (0.508, 0.916), P = 0.011]. There was a causal relationship between femoral neck bone mineral density and PhenoAge acceleration [OR = 1.452, (95%CI) = (1.007, 2.096), P = 0.046].

Conclusions: Epigenetic age acceleration was bi-directionally causally associated with osteoporosis. GrimAge acceleration increased the risk of decreased total body bone mineral density. Forearm bone mineral density accelerated GrimAge and femoral neck bone mineral density accelerated PhenoAge acceleration.

Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts in the kidneys, leading to kidney enlargement and progressive renal failure. Recent advances have indicated a pivotal role of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and PIWI-interacting RNAs (piRNAs), in the pathogenesis of PKD, potentially through regulating gene expression and cellular processes related to cyst formation, inflammation, and fibrosis. This review summarizes current knowledge of noncoding RNAs, explores their potential as biomarkers and therapeutic targets, and proposes potential directions for future research to further elucidate their roles in disease progression.

Objective: To retrospectively determine the incidence of recurrent microdeletion/microduplication syndromes in a prenatal cohort from Ningbo, China, and to evaluate pregnancy outcomes and live births in women carrying recurrent copy number variations (CNVs), this study aims to provide more clinical insights for assessing the variable penetrance of recurrent CNVs.

Method: A retrospective analysis was conducted on 7,645 pregnant women who underwent testing between 2019 and 2022 to investigate the incidence of locally recurrent microdeletion/microduplication syndromes and associated pregnancy outcomes. Chromosomal microarray analysis (CMA) identified 162 cases of recurrent CNVs. These cases were followed up to assess pregnancy outcomes, focusing on the implications of variable penetrance. The 162 patients were divided into two groups: Group 1 (n = 34), pregnancies with suspected genetic disease; Group 2 (n = 128), pregnancies with no apparent fetal abnormalities detected by ultrasonography. The study compared CNV pathogenicity and the rate of abnormal live births between the two groups.

Results: Among the 7,645 microarray tests, 162 cases of recurrent CNVs were identified across 34 distinct recurrent regions, yielding an incidence rate of 2.1%. The highest proportion was observed in pregnancies of advanced maternal age (45/162, 28%), followed by cases with high-risk serological screening results (40/162, 25%) and abnormal non-invasive prenatal testing (NIPT) results (38/162, 23%). CMA revealed that the most frequently involved chromosomes were chromosome 16, chromosome 22, and the sex chromosomes (X and Y): 3 recurrent regions on chromosome 16 affected 37 fetuses; 2 recurrent regions on chromosome 22 affected 28 fetuses; and 4 recurrent regions on sex chromosomes (X and Y) affected 47 fetuses. Follow-up analysis showed a pregnancy termination rate of 36.97% among the 162 cases. In Group 1, 37% (13/34) of women continued their pregnancies, and 3 of the live births exhibited postnatal congenital cardiac anomalies; the remaining had no reported anomalies. In Group 2, 41% (54/128) continued the pregnancy, with postnatal anomalies identified in 11 cases. A chi-square (χ²) test showed no statistically significant difference in the proportion of abnormal live births between the two groups (P > 0.001).

Conclusion: CMA enabled detection and analysis of recurrent CNVs in prenatal samples, offering insight into their clinical manifestations and associated pregnancy outcomes, particularly in cases with variable penetrance. Our findings enhance understanding of the clinical phenotypes of recurrent CNVs and provide additional data support for genetic counseling. Importantly, we found that fetuses carrying CNVs, despite the absence of structural anomalies, may face risks comparable to those with visible malformations. Therefore, we strongly recommend invasive prenatal diagnostic procedures when NIPT or serologic screening indicates abnormalities, as CMA-detected pathogenic CNVs can significantly impact prognosis and clinical decision making.

Gaucher disease (GD) is an autosomal recessive inborn error of metabolism caused by acid β-glucocerebrosidase deficiency, which presents with a wide spectrum of clinical manifestations, ranging from perinatal-lethal to asymptomatic forms. GD type 1 (GD1) is the most frequent visceral form, whereas types 2 (GD2) and 3 (GD3) are associated with neurodegeneration (neuronopathic GD, nGD) and share overlapping manifestations, presenting as a continuum of neurological disease severity. Traditionally, GD2 is the most severe form and has a rapidly progressive course with death by age two to four years. Currently available treatments for GD include enzyme replacement therapy and substrate reduction therapy to ameliorate visceral, hematologic, and skeletal abnormalities; however, they are not efficacious for neurological manifestations. More recently, ambroxol has been suggested as an augmentative pharmacological chaperone for nGD. This comparative case series of three patients aims to demonstrate the impact of early neonatal initiation of ambroxol on neurological outcomes in our index case (Patient A), compared to two other patients (Patients B and C) who began ambroxol treatment at 10 months and 4 years and 1 month of age, respectively, after a later diagnosis of nGD with already established neurological symptoms. Patient A has normal age-related developmental milestones at four years, while Patients B and C have persistence of developmental delay albeit some forward progression in the former. Our report highlights that early neonatal diagnosis and ambroxol therapy could potentially be a game changer in mitigating disease progression in nGD by modifying the natural history of GD2. Expanding newborn screening will facilitate early diagnosis and significantly impact clinical outcomes and quality of life in GD patients with early initiation of treatment.