Functional Neural Transplantation IV: Translation to Clinical Application, Part B

Dunnett is a behavioural neuroscientist who started a lifelong collaboration with the Björklund team in 1979 to explore the functional consequences of cell transplantation method in animal models of neurodegenerative disease, in particular involving cell replacement and repair of the basal ganglia. He has developed models and novel methods of motor and cognitive assessment to apply behavioural analysis not simply to assess functional efficacy of implanted cells, but as a tool to study the mechanisms of cell integration, circuit reconstruction and functional repair. In parallel his laboratory originated the first UK trial of cell transplantation in Huntington’s disease, and provides the source of clinical grade cells for further ongoing trials in Parkinson’s disease.

Anders Björklund is Senior Professor of neuroscience at Lund University (Sweden). His research career at Lund University spans over more than 50 years, and has resulted in a publication list that covers over 600 papers. His major achievements are in the field of cell transplantation and brain repair. He started this line of research in the mid 1970ies, based on the idea that immature neurons can be used to restore brain circuitry and promote functional recovery in animal models of neurodegenerative diseases. During this period, 1975-1985, his group pioneered this approach using cells obtained from the fetal brain. Anders and his clinical collaborators obtained permission to use tissue from aborted human fetuses in a series of open-label clinical trials in PD patients. Although the outcome of these trials has been quite variable, they have given proof-of-principle that immature dopamin neurons can survive and mature in the striatum in advanced PD patients, and restore dopamine neurotransmission in the area of the striatum re-innervated by the grafted neurons. Since the 1980ies the Lund neural transplantation program has been a leader in the development of restorative therapies in Parkinson ́s disease. Current efforts at the Wallenberg Neuroscience center are focused on the development of stem cell-derived dopamine neurons for transplantation, aimed at the development of transplantable neurons derived from human pluripotent stem cells for clinical application. In a parallel line of work Anders group has explored the use of viral vector-mediated gene transfer for neuroprotection and brain repair, with the aim to develop new therapeutic approaches for Parkinson ́s disease and other neurodegenerative disorders. In addition, he has pioneered the use of AAV vectors for overexpression of human -synuclein for induction of Parkinson-like neurodegeneration in the nigrostriatal system. This approach has provided a new tool for modeling of the progressive synuclein-induced disease process in animal models of PD.