Can cell and gene therapies improve cognitive symptoms in Parkinson's disease?

Advanced therapeutic medicinal products (ATMPs), including cell and gene therapies, are in development for Parkinson's disease (PD). In many cases, the goal is to replace the lost dopamine (DA), which is anticipated to improve motor dysfunctions associated with DA loss. However, it is less clear the extent to which these therapeutic interventions may impact on the wide range of cognitive symptoms that manifest as the disease progresses. Although the accepted perception is that cognitive symptoms are predominately non-DAergic in origin, in this commentary, it is argued that several, specific cognitive processes, such as habit formation, working memory and reward processing, have been reported to be DA-dependent. Furthermore, there is evidence of DAergic medications modulating these behaviours in PD patients. Finally, the potential for cell and gene ATMPs to influence these symptoms is considered. It is concluded that DA replacement through ATMPs is likely to improve certain DA-dependent symptoms, but only sparse clinical data are currently available and the ability to precisely titrate DA transmission is likely to be complex.