Cell rejuvenation is rapidly becoming a hot topic in the development of new treatments for a wide range of diseases.
Leading methods in the field of cell rejuvenation are being developed, utilizing epigenetic reprogramming to achieve this goal.
Epigenetics is the study of how lifestyle factors, both positive and negative (exercise, smoking, alcohol consumption, etc.), aging, disease, and injury affect the activity of our genes.
Throughout life, epigenetic markers (DNA methylation) accumulate on DNA, causing changes in gene expression patterns. These epigenetic changes build up over time and can lead to significant alterations in gene expression, with many crucial genes being suppressed.
Gene therapy is becoming increasingly popular, with many treatments being developed for various diseases. Unlike traditional gene therapies that directly alter genes, cell rejuvenation focuses on restoring cells to a more youthful state by removing epigenetic marks that suppress gene function.
Cell Rejuvenation: The ‘Yamanaka’ Factors
The Nobel Prize-winning discovery by Dr. Shinya Yamanaka that the expression of four transcription factors can return a cell to a pluripotent stem cell state by erasing epigenetic markers was a fundamental breakthrough in making this potential treatment feasible. However, a limiting factor for therapeutic efficacy when using all four Yamanaka factors is the erasure of cell identity, and the overexpression of one of these transcription factors (c-Myc) can lead to tumor formation.
Using partial epigenetic reprogramming by expressing only three of the transcription factor genes (Oct4, Sox2, and Klf4; collectively known as OSK) and eliminating the tumorigenic c-Myc gene allows cells to be rejuvenated and returned to a more youthful state while maintaining their original cell identity and avoiding teratoma formation.
As the population ages, the incidence of age-related eye diseases that lead to vision loss and eventual blindness continues to rise. While conditions like wet age-related macular degeneration have seen significant improvement with the use of VEGF inhibitors, other age-related eye diseases still lack effective long-term treatments.
Adeno-Associated Viral Vector
Treatments for disorders involving retinal ganglion cell (RGC) function, such as progressive glaucoma or non-arteritic anterior ischemic optic neuropathy (NAION), remain significantly ineffective or non-existent.
In recent years, there has been increasing interest in exploring the opportunities that gene therapy offers for hard-to-treat conditions like glaucoma and NAION. Several approaches are being evaluated to deliver these transcription factors to their target.
For example, an adeno-associated viral vector (AAV2) can be used to deliver OSK to RGCs via intravitreal injection (IVT). Using this system, OSK improves RGC function across multiple aging, glaucoma, and NAION models, from mice to non-human primates. Alternative methods using lipid nanoparticles to deliver mRNA are advancing, but they may still require improvements in targeting specificity for cells/organs.
The value of cell rejuvenation through partial epigenetic reprogramming is just beginning to be explored, with many age-related diseases poised to be addressed. With strong data supporting ocular indications, diseases like glaucoma and NAION may be among the first areas for therapeutic intervention. Epigenetic reprogramming models have been shown to impact multiple organs in the body. With improvements in organ-targeting approaches, the opportunity to treat age-related diseases through cell rejuvenation, not just for eye diseases but also for other tissues, certainly holds great promise.
Source: Labiotech
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