My understanding is that this field is still far from considering clinical trials. Being able to specifically and reliably promote this conversion remains a challenge. Designing a method to deliver the reprogramming strategy in a non-invasive manner also remains to be done. Several strategies are being considered to reprogram glia cells to neurons: suppression of TFs (e.g. PTBP1), expression of TFs (e.g. Ascl1, Dlx2, NeuroD1 etc.), miRNA (e.g. miRNA-124) and small molecules. For a therapeutic benefit for a specific condition, the right combination of targeted cell, microenvironment and reprogramming factors remain to be elucidated. Given the current state of research, there are many unknowns and risks, for e.g.:
- impact on the targeted glia populations and their functions. Right dosage and ensuring homeostatic processes maintain the population will be important
- impact on the microenvironment with potential beneficial or deleterious consequences
- off-target expressions and unintended disruptions
- all risks related to invasive approaches often used in animal models (e.g. AAV injection in midbrain in PD models), including toxicity