Parkinson's disease future or investigational therapies
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Future or Investigational Therapies
Gene therapy
Currently under investigation is gene therapy. This involves using a harmless 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.[1] 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.
Implantation of stem cells genetically engineered to produce dopamine or stem cells that transform into dopamine-producing cells has already started being used. These could not constitute cures because they do not address the considerable loss of activity of the dopaminergic neurons. Initial results have been unsatifactory, with patients still retaining their drugs and symptoms.
Continuous levodopa-carbidopa intestinal gel infusion
Continuous subcutaneous apomorphine
Neuroprotective treatments
Neuroprotective treatments are at the forefront of PD research, but are still under clinical scrutiny[2]. These agents could protect neurons from cell death induced by disease presence resulting in a slower pregression of disease. Agents currently under investigation as neuroprotective agents include apoptotic drugs (CEP 1347 and CTCT346), lazaroids, bioenergetics, antiglutamatergic agents and dopamine receptors[3]. Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitors selegiline[4] 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.[5] A significant problem was the excess release of dopamine by the transplanted tissue, leading to dystonias.[6] Research in African green monkeys suggests that the use of stem cells might in future provide a similar benefit without inducing dystonias.[7]
Nutrients
Nutrients have been used in clinical studies and are widely used by people with Parkinson's disease 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.[8] 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.[9] [10]
More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis.[11] Vitamin C and vitamin E in large doses are commonly used by patients in order to theoretically lessen the cell damage that occurs in Parkinson's disease. 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.[4]
Coenzyme Q10 has more recently been used for similar reasons. MitoQ is a newly developed synthetic substance that is similar in structure and function to coenzyme Q10.
Qigong
There have been two studies looking at qigong in Parkinson's disease. In a trial in Bonn, an open-label randomised pilot study in 56 patients found an improvement in motor and non-motor symptoms amongst patients who had undergone one hour of structured Qigong exercise per week in two 8-week blocks. The authors speculate that visualizing the flow of "energy" might act as an internal cue and so help improve movement.[12]
The second study, however, found Qigong to be ineffective in treating Parkinson's disease. In that study, researchers used a randomized cross-over trial to compare aerobic training with Qigong in advanced Parkinson's disease. Two groups of PD patients were assessed, had 20 sessions of either aerobic exercise or qigong, were assessed again, then after a 2 month gap were switched over for another 20 sessions, and finally assessed again. The authors found an improvement in motor ability and cardiorespiratory function following aerobic exercise, but found no benefit following Qigong. The authors also point out that aerobic exercise had no benefit for patients' quality of life.[13]
Botox
Recently, Botox injections are being investigated as a non-FDA approved possible experimental treatment.[14]
References
- ↑ Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D, During MJ (2007). "Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial". Lancet. 369 (9579): 2097–105. doi:10.1016/S0140-6736(07)60982-9. PMID 17586305.
- ↑ Bonuccelli U,
Del Dotto P (2006). "New pharmacologic horizons in the treatment of Parkinson disease". Neurology. 67 (2): 30–38. line feed character in
|author=at position 14 (help) - ↑ Djaldetti R, Melamed E (2002). "New drugs in the future treatment of Parkinson's disease". J. Neurol. 249 Suppl 2: II30–5. doi:10.1007/s00415-002-1206-2. PMID 12375061.
- ↑ 4.0 4.1 "Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group". N. Engl. J. Med. 328 (3): 176–83. 1993. PMID 8417384.
- ↑ Freed CR, Greene PE, Breeze RE; et al. (2001). "Transplantation of embryonic dopamine neurons for severe Parkinson's disease". N. Engl. J. Med. 344 (10): 710–9. PMID 11236774.
- ↑ Redmond DE (2002). "Cellular replacement therapy for Parkinson's disease--where we are today?". The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry. 8 (5): 457–88. PMID 12374430.
- ↑ Redmond E; et al. (2007). "Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells". Procedings of the National Academy of Sciences. 104 (29).
- ↑ Lemoine P, Robelin N, Sebert P, Mouret J (1986). "La L-tyrosine : traitement au long cours de la maladie de Parkinson [L-tyrosine : A long term treatment of Parkinson's Disease]". Comptes rendus academie des sciences (in French). 309: 43–47.
- ↑ Birkmayer W, Birkmayer JG (1986). "Iron, a new aid in the treatment of Parkinson patients". J. Neural Transm. 67 (3–4): 287–92. PMID 3806082.
- ↑ Editors Przuntek H , Riederer P, ed. (1989). Early diagnosis and preventive therapy in Parkinson's disease. Springer. pp. p. 323. ISBN 0-387-82080-9.
- ↑ "Dopamine biosynthesis" (Word doc). University of Chicago Personal Web Pages. Retrieved 2006-11-04.
- ↑ Schmitz-Hubsch T (2006). "Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study". Mov Disord. 21 (4): 543–548. PMID 16229022.
- ↑ Burini D, Farabollini B, Iacucci S; et al. (2006). "A randomised controlled cross-over trial of aerobic training versus Qigong in advanced Parkinson's disease". Europa medicophysica. 42 (3): 231–8. PMID 17039221.
- ↑ Template:Citeref patent