Advanced therapeutic medicinal products (ATMPs) are a new class of therapies based on genes, cells or tissues, that seek to stop the progress of a disease or indeed correct the dysfunction associated with a disorder through repair and regeneration strategies. While interventions are largely specific to each disease, there are several common approaches which are being employed. Three main classes of ATMP are described by the European regulatory authority, the European Medicines Agency (EMA); gene therapy, somatic cell therapy and tissue engineered medicines (collectively referred to here as ATMPs or cell and gene therapy). Gene therapy uses tools to insert genes into cells that are intended to manage or treat the disease, while the cell therapy approach uses cells themselves to either replace, repair or regenerate human tissues. While some ATMPs have reached the point of clinical implementation in other fields (for example, oncology and spinal muscular atrophy), ATMP approaches for neurodegenerative diseases are still in their relative infancy, being either in late-stage preclinical development or phase 2 safety and initial efficacy studies.

Active development of cell and gene therapies is occurring across a spectrum of neurodegenerative disease including Parkinson's (PD), Alzheimer's disease and multiple sclerosis (MS) as well as rarer disorders such as Huntington's disease (HD) (see reviews, Jensen, Gøtzsche, & Woldbye, 2021; Merola et al., 2021; Prasad & Hung, 2021). Each of these disorders, responsible for progressive motor and/or cognitive dysfunctions, involves a pathological cell death process leading to the loss of specific neuronal subtypes and in many cases the additional involvement of at least one toxic protein species. Cell therapies, delivered directly to the brain, are proposed generally as mechanisms to replace the lost neuronal connectivity and/or neurotransmitters. Gene therapy approaches offer a range of functions, either replacing missing neurotransmission or proposing to slow or stall the pathological processes by either reducing production of the toxic proteins or providing neurotrophic support to the remaining cells. In the case of stroke and spinal cord injury where the insult is more acute, reparative and restorative therapies are also being developed using the same strategies.

Clinical trials of ATMPs for neurodegenerative diseases are highly involved, complex trials requiring brain surgery or lumbar punctures with extensive pre and post intervention outcomes assessment for evaluation of safety and efficacy. The design and conduct of clinical trials in this area is varied but often, from a participant's perspective, differs significantly to pharmacological trials, being akin more to neurosurgical trials for elective tissue ablations or deep brain stimulation (DBS). While in some instances in ATMP trials there are repeat administrations of the therapeutic agent, many are delivered as a single “one-hit” procedure. As such, these trials require a significant commitment from a participant to undergo a procedure at considerable personal risk. The cells or viral vectors are irreversibly delivered into the brain and while tested to the best of abilities in the laboratory, their safety is at this point unknown. Yet for participants significant hope may be engendered; hope that they may see a long-lasting impact not just on their symptoms but for the first time altering the course of their disease (Cho, Miller, & Kim, 2020; de Bot, 2019; Keränen, Pasternack, & Halkoaho, 2017). The reality, however, is that the success rate of trials in neurodegenerative diseases is remarkably poor overall, especially when neuroprotective, disease modifying or regenerative approaches have been trialed (Feustel, MacPherson, Fergusson, Kieburtz, & Kimmelman, 2020). This “hope” is perhaps therefore better described therefore as therapeutic optimism, the belief that they will experience direct medical benefit from early-stage interventions. It is against this unique backdrop that here we consider how those living with the disease are heard, with a specific look at how the participant voice is considered in trials. While it is not in doubt that there is a significant demand from the patient community for treatments to better manage their disease (Andrejack & Mathur, 2020), we explore what is known, how the public perceive these advanced interventions and consider this alongside the challenges they may face in bravely undertaking clinical trials.