I am thrilled to introduce our new initiative that harnesses the potential of neuronal reprogramming to revolutionize the treatment of incurable neurological disorders. In support of our initiative, we have been awarded a New Frontiers in Research Fund - Transformation 2023 Grant to fund a Canadian-led interdisciplinary team of 24 talented researchers from across Canada and Europe, who together aim to develop novel gene therapies for brain repair.

Neurons in the adult brain are born in the embryo and must survive to function throughout life, making neuronal death a pathological phenomenon in adulthood. At the heart of our mission lies the possibility of using direct neuronal reprogramming as a therapeutic strategy to replace lost neurons by changing the identities of the brain cells that remain, offering hope for patients facing conditions deemed untreatable.

Our approach begins with a solid understanding of the genes that promote neurogenesis – the process governing the generation of new neurons – that has been gained via the power of genetics, largely using mice models. Through careful research, we have identified neuron-specifying factors that are capable of driving neurogenesis in both embryonic and adult neural stem cells. This knowledge is now being applied to tackle the more challenging scenario, whereby brain astrocytes – another brain cell type – are converted into induced neurons (iNeurons), thereby replenishing depleted neuronal pools, a hallmark of several neurological disorders.

I am thrilled to introduce our new initiative that harnesses the potential of neuronal reprogramming to revolutionize the treatment of incurable neurological disorders. In support of our initiative, we have been awarded a New Frontiers in Research Fund - Transformation 2023 Grant to fund a Canadian-led interdisciplinary team of 24 talented researchers from across Canada and Europe, who together aim to develop novel gene therapies for brain repair.

Neurons in the adult brain are born in the embryo and must survive to function throughout life, making neuronal death a pathological phenomenon in adulthood. At the heart of our mission lies the possibility of using direct neuronal reprogramming as a therapeutic strategy to replace lost neurons by changing the identities of the brain cells that remain, offering hope for patients facing conditions deemed untreatable.

Our approach begins with a solid understanding of the genes that promote neurogenesis – the process governing the generation of new neurons – that has been gained via the power of genetics, largely using mice models. Through careful research, we have identified neuron-specifying factors that are capable of driving neurogenesis in both embryonic and adult neural stem cells. This knowledge is now being applied to tackle the more challenging scenario, whereby brain astrocytes – another brain cell type – are converted into induced neurons (iNeurons), thereby replenishing depleted neuronal pools, a hallmark of several neurological disorders.

While our successes at the cellular level are promising, translating these findings to animal models and humans presents significant challenges, including lower conversion efficiency and species-specific variations in timing. Undeterred, our multidisciplinary team is committed to overcoming these hurdles by enhancing the specificity of the transcription factor cargo, engineering precise gene delivery tools, and developing translatable outcome measures to assess the impact of neuronal conversion on disease progression. Critical to our approach is the collaboration of experts from diverse disciplines, including computational science, life sciences, physical sciences, and biomedical engineering. Our team will develop novel algorithms, empirically test reprogramming strategies, and implement cutting-edge outcome measures to drive clinical translation.

Equally essential to our success is the inclusion of voices beyond the laboratory – people with lived experience, families, clinicians, and ethicists. Through our Cross-Cutting Platform of Advisory Panels, we seek to ensure that our research is not only scientifically rigorous but also ethically and socially responsible. By engaging key stakeholders and fostering trust, we strive to advance equitable access and health justice for all.

Together, we embark on this journey to unlock the full potential of neuronal reprogramming and usher in a new era of hope for those affected by neurological disorders.

Sincerely,

Dr. Carol Schuurmans, Ph.D. (NPI)