Telomere recapping via gene therapy as a beneficial strategy for cardio-renal syndrome type 4 - PubMed
a day ago
- #gene therapy
- #telomere recapping
- #cardio-renal syndrome
- Cardio-renal syndrome type 4 (CRS4) is characterized by heart failure caused by chronic kidney disease (CKD).
- Short leukocyte telomere lengths in CKD patients correlate with increased cardiovascular mortality.
- Gene therapy JV101, using AAV9 to overexpress modified human telomerase reverse transcriptase (modhTERT), was tested in CRS4 models.
- modhTERT recapped myocardial telomeres and reversed cardiac dysfunction, hypertrophy, fibrosis, and mitochondrial dysfunction in mouse models.
- The therapeutic effects of modhTERT were long-term and persistent, unlike beta-blockers which only delayed heart failure progression.
- modhTERT also improved kidney function in CKD murine models and reversed contractile dysfunction in human iPSC-derived cardiomyocytes.
- Transcriptomic analysis showed modhTERT reversed repression of genes involved in mitochondrial metabolism.
- The study provides proof-of-concept for telomere recapping gene therapy as a treatment for CRS4.