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

One of the PD therapies which are under investigation is gene therapy. In this therapy we enter a virus into subthalamic nucleus cells of the brain. This virus has a gene coding an enzyme called glutamic acid decarboxylase (GAD) and this enzyme can catalyses the production of GABA.[1]

Continuous levodopa-carbidopa intestinal gel infusion

Some studies suggest that levodopa-carbidopa intestinal gel infusion is useful in treatment of PD symptoms and it’s even more effective than intermittent dosing of immediate-release oral carbidopa-levodopa.[2][3][4] the adverse effects of this procedure are abdominal pain, skin infection, peritonitis and aspiration.[5]

Continuous subcutaneous apomorphine

There is some evidence suggesting that continuous subcutaneous apomorphine infusion (CSAI) can reduce "off" time and dyskinesia in PD. there are some tests which we have to check before starting this treatment including: ECG, direct antiglobulin (coombs) and complete blood count. skin nodules at injection site is the most common complication of this treatment.[6][7]

Neuroprotective treatments

Neuroprotective drugs such as apoptotic drugs (CEP1347 and CTCT346), lazaroids, bioenergetics and antiglutamatergic agents.[8][9]

Neural transplantation

One of the under investigation therapies is transplantation of dopamine-producing cell into brain. In one of the studies it caused an improvement in the symptoms in PD patients under 60.[10] One of the side effects of this therapy is that it can cause dystonia by increased amount of dopamine.[11] To solve this side effect a study in African monkeys suggest using stem cells.[12]

Nutrients

Nutrients can be very useful in controlling PD symptoms. L-tyrosine, the precursor of L-dopa is one of these nutrients.[13] The other nutrient is ferrous iron which is the essential co factor for L-dopa biosynthesis.[14][15]

Other nutrients includes THFA, NADH and pyridoxine_ coenzymes, coenzymes precursors[16], vitamin C and vitamin E in large doses. These vitamins are necessary for some enzymes such as superoxide dismutase and catalase to nullify the superoxide anions in damaged cells.[17]

Exercise

In one of the studies it was suggested that qigong exercise can improve PD patient’s symptoms by visualizing the flow of energy[18] But in another study there were evidences showing that aerobic exercise in beneficial for symptom control in PD patients.[19]

Botox

Botox injections are under investigation for treatment of PD symptoms.[20]

References

  1. 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.
  2. Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A (February 2014). "Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study". Lancet Neurol. 13 (2): 141–9. doi:10.1016/S1474-4422(13)70293-X. PMC 4643396. PMID 24361112.
  3. Wirdefeldt K, Odin P, Nyholm D (May 2016). "Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review". CNS Drugs. 30 (5): 381–404. doi:10.1007/s40263-016-0336-5. PMID 27138916.
  4. Timpka J, Nitu B, Datieva V, Odin P, Antonini A (2017). "Device-Aided Treatment Strategies in Advanced Parkinson's Disease". Int. Rev. Neurobiol. 132: 453–474. doi:10.1016/bs.irn.2017.03.001. PMID 28554418.
  5. Lang AE, Rodriguez RL, Boyd JT, Chouinard S, Zadikoff C, Espay AJ, Slevin JT, Fernandez HH, Lew MF, Stein DA, Odin P, Fung VS, Klostermann F, Fasano A, Draganov PV, Schmulewitz N, Robieson WZ, Eaton S, Chatamra K, Benesh JA, Dubow J (April 2016). "Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials". Mov. Disord. 31 (4): 538–46. doi:10.1002/mds.26485. PMC 5064722. PMID 26695437.
  6. Wenzel K, Homann CN, Fabbrini G, Colosimo C (July 2014). "The role of subcutaneous infusion of apomorphine in Parkinson's disease". Expert Rev Neurother. 14 (7): 833–43. doi:10.1586/14737175.2014.928202. PMID 24917215.
  7. Trenkwalder C, Chaudhuri KR, García Ruiz PJ, LeWitt P, Katzenschlager R, Sixel-Döring F, Henriksen T, Sesar Á, Poewe W, Baker M, Ceballos-Baumann A, Deuschl G, Drapier S, Ebersbach G, Evans A, Fernandez H, Isaacson S, van Laar T, Lees A, Lewis S, Martínez Castrillo JC, Martinez-Martin P, Odin P, O'Sullivan J, Tagaris G, Wenzel K (September 2015). "Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations". Parkinsonism Relat. Disord. 21 (9): 1023–30. doi:10.1016/j.parkreldis.2015.06.012. PMID 26189414.
  8. 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.
  9. 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)
  10. 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.
  11. 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.
  12. 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).
  13. 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.
  14. 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.
  15. 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.
  16. "Dopamine biosynthesis" (Word doc). University of Chicago Personal Web Pages. Retrieved 2006-11-04.
  17. "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.
  18. 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.
  19. 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.
  20. Template:Citeref patent

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