Publications by authors named "P Bross"
On December 16, 2022, the FDA approved the adenoviral vector-based gene therapy nadofaragene firadenovec-vncg (brand name Adstiladrin) for the treatment of adult patients with high-risk bacillus Calmette-Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS). The product represents the first approved adenoviral vector-based gene therapy and the first approved gene therapy for bladder cancer. Determination of efficacy was based on results from Study rAd-IFN-CS-003 (Study CS-003), a single-arm trial in 98 evaluable patients with BCG-unresponsive NMIBC with CIS who received intravesical instillations of the gene therapy product (75 mL of nadofaragene firadenovec at 3 × 1011 viral particles per mL) once every 3 months.
View Article and Find Full Text PDFThe mitochondrial unfolded protein response (UPR) maintains mitochondrial quality control and proteostasis under stress conditions. However, the role of UPR in aggressive and resistant prostate cancer is not clearly defined. We show that castration-resistant neuroendocrine prostate cancer (CRPC-NE) harbored highly dysfunctional oxidative phosphorylation (OXPHOS) Complexes.
View Article and Find Full Text PDFArticle Synopsis
- Hypomyelinating leukodystrophies are genetic disorders with severe myelin deficiency, resulting in developmental delays, nystagmus, hypotonia, spasticity, and ataxia.
- Variants in the HSP60 chaperonin protein have been linked to various neurological disorders, and recent findings highlight a group of patients with new heterozygous variants related to a unique hypomyelinating disorder.
- Clinical evaluations and genetic assays in a study of three patients showed early symptoms of nystagmus and hypotonia that progressed to spasticity, confirming that defective chaperonin assembly likely contributes to these disorders.
Article Synopsis
- HSP60 is a crucial mitochondrial chaperone that helps maintain cellular function, and its dysregulation is linked to conditions like cancer and diabetes, as well as neurodevelopmental issues in patients with certain gene variants.
- Two model systems—engineered HEK cells and zebrafish knockout larvae—were used to investigate the impact of HSP60 deficiency, employing techniques like RNASeq, proteomics, and metabolomics analysis.
- Findings reveal that HSP60 deficiency results in a downregulated mitochondrial proteome, triggers stress responses, and disrupts cholesterol biosynthesis, leading to lipid buildup in the knockout larvae and explaining myelination issues in affected patients.
Background: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC.
Objective: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies.