User:HAL333/Parkinson's research

Research
, no disease-modifying drugs (drugs that target the causes or damage) are approved for Parkinson's, so this is a major focus of Parkinson's research. Active research directions include the search for new animal models of the disease and studies of the potential usefulness of gene therapy, stem cell transplants, and neuroprotective agents. To aid in earlier diagnosis, research criteria for identifying prodromal biomarkers of the disease have been established.

Gene therapy
Gene therapy typically involves the use of a noninfectious virus to shuttle genetic material into a part of the brain. Approaches have involved the expression of growth factors to prevent damage (Neurturin – a GDNF-family growth factor), and enzymes such as glutamic acid decarboxylase (GAD – the enzyme that produces GABA), tyrosine hydroxylase (the enzyme that produces L-DOPA) and catechol-O-methyl transferase (COMT – the enzyme that converts L-DOPA to dopamine). No safety concerns have been reported but the approaches have largely failed in phase two clinical trials. The delivery of GAD showed promise in phase two trials in 2011, but while effective at improving motor function, was inferior to DBS. Follow-up studies in the same cohort have suggested persistent improvement.

Some therapies seek to upregulate expression of DOPA decarboxylase and other enzymes in the dopamine synthetic pathway to increase overall dopamine production. Others target GBA1 mutations, which are believed to result in lysosome dysfunction, altered protein homeostasis, and ultimately alpha-synuclein aggregation.

The three most studied gene targets are alpha-synuclein (AS), glucocerebrosidase (GBA1), and leucine-rich repeat most studied gene targets, alpha-synuclein (AS), glucocerebrosidase (GBA1), and leucine-rich repeat kinase-2 (LRRK2).

Neuroprotective treatments
A vaccine that primes the human immune system to destroy alpha-synuclein, PD01A, entered clinical trials and a phase one report in 2020 suggested safety and tolerability. In 2018, an antibody, PRX002/RG7935, showed preliminary safety evidence in stage I trials supporting continuation to stage II trials.

Cell-based therapies
In contrast to other neurodegenerative disorders, many Parkinson's symptoms can be attributed to the loss of a single cell type: mesencephalic dopaminergic (DA) neurons. Consequently, DA neuron regeneration is a promising therapeutic approach. Although most initial research sought to generate DA neuron precursor cells from fetal brain tissue, pluripotent stem cells—particularly induced pluripotent stem cells (iPSCs)—have become an increasingly popular tissue source.

Both fetal and iPSC-derived DA neurons have been transplanted into patients in clinical trials. Although some patients see improvements, the results are highly variable. Adverse effects, such as dyskinesia arising from excess dopamine release by the transplanted tissues, have also been observed.

Pharmaceutical
Antagonists of adenosine receptors (specifically A2A) have been explored for Parkinson's. Of these, istradefylline has emerged as the most successful medication and was approved for medical use in the United States in 2019. It is approved as an add-on treatment to the levodopa/carbidopa regime.