Gene and Cell-Based Therapies for Parkinson's Disease: Where Are We?

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that carries large health and socioeconomic burdens. Current therapies for PD are ultimately inadequate, both in terms of symptom control and in modification of disease progression. Deep brain stimulation and infusion therapies are the current mainstay for treatment of motor complications of advanced disease, but these have very significant drawbacks and offer no element of disease modification. In fact, there are currently no agents that are established to modify the course of the disease in clinical use for PD. Gene and cell therapies for PD are now being trialled in the clinic. These treatments are diverse and may have a range of niches in the management of PD. They hold great promise for improved treatment of symptoms as well as possibly slowing progression of the disease in the right patient group. Here, we review the current state of the art for these therapies and look to future strategies in this fast-moving field.

Nanobodies as allosteric modulators of Parkinson’s disease-associated LRRK2

“…One possible approach is to deliver the genes encoding the Nbs using a viral vector-based system (47). The field of gene therapy for the nervous system has undergone explosive growth in the last 5 years (48,49), and gene therapy strategies have also been developed for PD (50)(51)(52)(53). Different approaches for the development of the Nbs into next-generation therapeutics to target LRRK2 in PD are currently being explored.…”

Human Neural Stem Cells for Cell-Based Medicinal Products

“…Most often the tissue is collected from elective termination of pregnancies, which is a cause of major ethical concerns and opposed by many on moral and religious grounds [ 12 ]. The idea that the use of fetal tissue could encourage women to abort has been put forward by pro-life activists, although there is no evidence that using fetal tissue for therapeutic or commercial purposes increases the number of elected abortions [ 13 ]. Nevertheless, the use of fNSC is socially controversial and strictly regulated, being prohibited in some countries [ 14 ].…”

“…Other logistic and safety issues with iPSC are the low reprogramming efficiency, tumorigenesis related to insertional mutagenesis, and to the fact that reprogramming enriches mutations in oncogenes [ 61 ], and the propensity of cell lines to give rise to derivatives from a specific germ layer [ 62 ]. Nevertheless, many of these reprogramming issues are more theoretical than practical and may not be relevant for iPSC-NSC clinical safety [ 13 ]. In fact, clinical trials using iPSC-NSC are underway ( Table 1 ).…”

Therapeutic Advances in Movement Disorders

“…Surgical treatment approaches have transformed the management of moderate to advanced PD care and, besides the discovery of levodopa, represent one of the greatest therapeutic [15]. Buttery and Barker end the PD section on a hopeful note, with a wonderful review of where we are now with gene-and cell-based therapies [16], many of which are in ongoing high-profile clinical trials. They highlight the great promise for these approaches, some of which may allow for slowing progression of the disease or medication reduction, without the need for implanted hardware.…”