Gene Therapy
Currently under investigation is gene therapy. This involves using a non-infectious virus to shuttle a gene into a part of the brain called the subthalamic nucleus (STN). The gene used leads to the production of an enzyme called glutamic acid decarboxylase (GAD), which catalyses the production of a neurotransmitter called GABA. GABA acts as a direct inhibitor on the overactive cells in the STN.
GDNF infusion involves the infusion of GDNF (glial-derived neurotrophic factor) into the basal ganglia using surgically implanted catheters. Via a series of biochemical reactions, GDNF stimulates the formation of L-dopa. GDNF therapy is still in development.
Neuroprotective Treatments
Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny. These agents could protect neurons from cell death induced by disease presence resulting in a slower progression of disease. Agents currently under investigation as neuroprotective agents include anti-apoptotic drugs (CEP 1347 and CTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors. Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitors selegiline and rasagiline, dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10.
Neural transplantation
The first prospective randomised double-blind sham-placebo controlled trial of dopamine-producing cell transplants failed to show an improvement in quality of life although some significant clinical improvements were seen in patients below the age of 60. A significant problem was the excess release of dopamine by the transplanted tissue, leading to dystonias. Research in African green monkeys suggests that the use of stem cells might in future provide a similar benefit without inducing dystonias.
Alternative Treatments
Nutrients have been used in clinical studies and are used by people with PD in order to partially treat PD or slow down its deterioration. The L-dopa precursor L-tyrosine was shown to relieve an average of 70% of symptoms. Ferrous iron, the essential cofactor for L-dopa biosynthesis was shown to relieve between 10% and 60% of symptoms in 110 out of 110 patients.
More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis. Vitamin C and vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in PD. This is because the enzymes superoxide dismutase and catalase require these vitamins in order to nullify the superoxide anion, a toxin commonly produced in damaged cells. However, in the randomized controlled trial, DATATOP of patients with early PD, no beneficial effect for vitamin E compared to placebo was seen.
''Mucuna pruriens'', is a natural source of therapeutic quantities of L-dopa, and has been under some investigation.
