More than a participant in trials of cell and gene therapy: Hearing the voices of people living with neurodegenerative diseases.

With the advent of novel advanced therapy medicinal products (ATMPs) for neurodegenerative diseases, their pathway to clinical trials and the therapeutic landscape has highlighted some new challenges, many of which are outlined in other chapters of this volume. The practical considerations of all these aspects from basic research and animal models through to clinical trials and eventual clinical implementation are significant. By and large, the major voices surrounding these challenges are the scientists and clinical teams who both develop the interventions and design and deliver the clinical trials to test these novel ATMPs. Their expertise is of course essential, but there is a key voice that can add considerable benefit to the pipeline, that of the lived experience of the disease being treated and the new intervention being considered. While still in their relative infancy in neurodegenerative disease, some ATMPs are already in clinical application in other disease areas, mainly cancer and inherited disorders. This more advanced status has raised some interesting questions about the role of the patient voice across all aspects of the therapeutic research and clinical delivery pipeline. This chapter highlights what has been learnt from the patient voice in their understanding and perspectives of ATMPs and in their experiences of clinical trials in neurodegenerative diseases to date. We discuss when, and how, including people living with neurodegenerative disease is of value in the development and implementation of ATMPs and the questions this collaborative effort can allow us to answer.

GDNF and Parkinson's Disease: Where Next? A Summary from a Recent Workshop.

The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.