Parkinson disease - Emerging treatments

Exenatide

A glucagon‐like peptide‐1 (GLP‐1) receptor agonist. One Cochrane review concluded that exenatide may improve motor impairment for people with PD, and this effect may persist beyond the treatment period. The effectiveness of exenatide for improving health-related quality of life, activities of daily living, nonmotor outcomes, and psychological outcomes is unclear.[173]

Transcranial magnetic stimulation

Noninvasive brain stimulation by repetitive transcranial direct current stimulation (rTMS) modulates cortical excitability by applying a direct current to the skull. Some short-term benefits of rTMS on walking performance (including freezing of gait) and depression in patients with PD have been reported, but evidence is equivocal and further trials are needed.[174][175][176][177][178]

Tissue/cell-based therapy

TRANSEURO, a multicenter collaborative study for the treatment of PD, has three principal objectives: to demonstrate that dopaminergic cell replacement can be improved by careful attention to tissue preparation and delivery, patient selection, and immunosuppressive treatment; to show that dopaminergic cell replacement can be clinically efficacious; and to develop a protocol that can serve as a template for all future clinical trials in the cell therapy field, including of stem cell-based therapies.[179] TRANSEURO Opens in new window A study involving grafting of fetal tissue into the brains of patients with PD (to help replace and rebuild lost dopamine) is under way, and a trial using embryonic cell-derived dopaminergic neuroblasts is planned.[180] A small investigational cell transplantation therapy study using human neural stem cells is also under way.[181] ISC-hpNSC, a cellular therapeutic consisting of human parthenogenetic neural stem cells (hpNSC), will be injected intracerebrally to the striatum and substantia nigra of patients with PD. The main study objective is to evaluate the safety of the cell transplantation.[182]

Gene therapy

Some experimental gene therapies for PD have been investigated, but showed limited efficacy in early clinical trials. A major challenge is real-time visualization of vector delivery, which limits optimization of distribution; one technique being assessed is intraoperative MRI-guided infusion.[183][184]

Immunotherapy targeting alpha-synuclein

Accumulation of toxic forms of alpha-synuclein is implicated in neuronal death in PD. Targeting this protein with immunization or antibody-based therapy via a vaccine is of interest, but issues related to specificity of targeting toxic forms of alpha-synuclein must be addressed.[185][186] Trials of cinpanemab and prasinezumab (human-derived monoclonal antibodies targeting alpha-synuclein) failed to show efficacy in preventing disease progression in patients with early PD.[187][188]

Dipraglurant

Dipraglurant, a glutamate receptor modulator, has received orphan drug designation from the Food and Drug Administration (FDA) for the management of levodopa-induced dyskinesia in PD.[189] A phase 2/3 trial is under way.[190]

Novel apomorphine formulations

Apomorphine can be given by continuous infusion in some countries.[162] Intranasal delivery of apomorphine is being researched.

K0706

K0706 is a tyrosine kinase inhibitor that has been shown to have neuroprotective activity in an animal model. A phase 2 study is under way to investigate the safety and efficacy of K0706 in patients with early PD who have not yet started dopaminergic therapy.[191]

High-intensity exercise in early PD

The effects of 12 months of high-intensity endurance treadmill exercise on changes in the Movement Disorder Society-Unified Parkinson Disease Rating Scale (MDS-UPDRS) Part III score among patients with early-stage PD who have not yet started dopaminergic therapy is being investigated in one phase 3 randomized study.[192]