Recent Advances in Neuroimaging Techniques to Assist Clinical Trials on Cell-Based Therapies in Neurodegenerative Diseases.

Abstract

Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are progressive disorders for which curative therapy is still lacking. Cell-based therapy aims at replacing dysfunctional cellular populations by repairing damaged tissue and by enriching the microenvironment of selective brain areas, and thus constitutes a promising disease-modifying treatment of neurodegenerative diseases. Scientific research has engineered a wide range of human-derived cellular populations to help overcome some of the logistical, safety, and ethical issues associated with this approach. Open-label studies and clinical trials in human participants have used neuroimaging techniques, such as positron emission tomography (PET) and magnetic resonance imaging (MRI), to assess the success of the transplantation, to evaluate the functional integration of the implanted tissue into the host environment and to understand the pathophysiological changes associated with the therapy. Neuroimaging has constituted an outcome measure of large, randomized clinical trials, and has given answers to clarify the pathophysiology underlying some of the complications linked with this therapy. Novel PET radiotracers and MRI sequences for the staging of neurodegenerative diseases and to study alterations at the molecular level significantly expands the translational potential of neuroimaging to assist pre-clinical and clinical research on cell-based therapy in these disorders. This concise review summarizes the current use of neuroimaging in human studies of cell-based replacement therapy and focuses on the future applications of PET and MRI techniques to evaluate the pathophysiology and treatment efficacy, as well as to aid patient selection and as an outcome measure to improve treatment success.