A research team from the University of Padua and the Veneto Institute of Molecular Medicine (VIMM), led by Onelia Gagliano and Cecilia Laterza, has developed an innovative method to generate human neurons more rapidly, efficiently, and cost-effectively than traditional techniques. The study, EEarly Reprogramming Intermediates Enable Direct Neuronal Conversion Via NGN2, published in the Journal of Molecular Neuroscience, shows that it is possible to obtain neurons from patients’ skin cells in just 12 days, compared to the 6–8 weeks required by conventional methods.

The new strategy is based on a short phase of partial reprogramming lasting about 3 days, followed by 9 days of neuronal induction, avoiding the full transition through a pluripotent stem cell state. The researchers identified a “time window” of high cellular plasticity, in which cells—no longer fibroblasts but not yet stem cells—are particularly responsive to signals that guide their transformation into neurons. In this phase, activating a single key gene, NGN2, is sufficient to effectively direct the conversion.

This approach addresses a crucial challenge in neuroscience research: the inability to directly study patients’ neurons. Generating neurons in the lab makes it possible to analyze diseases such as Alzheimer’s, Parkinson’s, and ALS in human cells, improving the understanding of disease mechanisms and making drug testing more reliable than with animal models. Moreover, compared to existing techniques, the new method reduces time, costs, and risks related to residual stem cells, while also improving overall efficiency.

The potential applications are broad and include studying neurological diseases, large-scale drug screening, and developing personalized medicine approaches. Future research will focus on verifying the full functional maturity of the generated neurons, further investigating cellular plasticity mechanisms, and applying the protocol to patient-derived cells to validate its effectiveness in real disease models.

“We move from a process that can take 6–8 weeks overall to just under two weeks, avoiding full stabilization in a pluripotent state,” explains Professor Onelia Gagliano. “We also identified a ‘time window’ of particular cellular plasticity: an intermediate state in which the cell is no longer a fibroblast but has not yet become a true stem cell. It is precisely during this transition phase that it is most ‘receptive’ to the signals that guide it to become a neuron.”