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=== Continuous levodopa-carbidopa intestinal gel infusion ===
=== Continuous levodopa-carbidopa intestinal gel infusion ===
 
Some studies suggest that [[levodopa]]-[[carbidopa]] intestinal gel infusion is useful in treatment of [[Parkinson's disease|PD]] [[symptoms]] and it’s even more effective than intermittent dosing of immediate-release oral [[carbidopa]]-[[levodopa]].<ref name="pmid24361112">{{cite journal |vauthors=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 |title=Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study |journal=Lancet Neurol |volume=13 |issue=2 |pages=141–9 |date=February 2014 |pmid=24361112 |pmc=4643396 |doi=10.1016/S1474-4422(13)70293-X |url=}}</ref><ref name="pmid27138916">{{cite journal |vauthors=Wirdefeldt K, Odin P, Nyholm D |title=Levodopa-Carbidopa Intestinal Gel in Patients with Parkinson's Disease: A Systematic Review |journal=CNS Drugs |volume=30 |issue=5 |pages=381–404 |date=May 2016 |pmid=27138916 |doi=10.1007/s40263-016-0336-5 |url=}}</ref><ref name="pmid28554418">{{cite journal |vauthors=Timpka J, Nitu B, Datieva V, Odin P, Antonini A |title=Device-Aided Treatment Strategies in Advanced Parkinson's Disease |journal=Int. Rev. Neurobiol. |volume=132 |issue= |pages=453–474 |date=2017 |pmid=28554418 |doi=10.1016/bs.irn.2017.03.001 |url=}}</ref> the [[adverse effects]] of this procedure are [[abdominal pain]], [[skin infection]], [[peritonitis]] and [[aspiration]].<ref name="pmid26695437">{{cite journal |vauthors=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 |title=Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials |journal=Mov. Disord. |volume=31 |issue=4 |pages=538–46 |date=April 2016 |pmid=26695437 |pmc=5064722 |doi=10.1002/mds.26485 |url=}}</ref>
=== Continuous subcutaneous apomorphine ===
=== Continuous subcutaneous apomorphine ===
 
There is some evidence suggesting that continuous subcutaneous apomorphine infusion (CSAI) can reduce "off" time and [[dyskinesia]] in [[Parkinson's disease|PD]]. there are some tests which we have to check before starting this treatment including: [[ECG]], [[Direct antiglobulin test|direct antiglobulin]] (coombs) and [[complete blood count]]. [[skin nodules]] at injection site is the most common [[complication]] of this treatment.<ref name="pmid24917215">{{cite journal |vauthors=Wenzel K, Homann CN, Fabbrini G, Colosimo C |title=The role of subcutaneous infusion of apomorphine in Parkinson's disease |journal=Expert Rev Neurother |volume=14 |issue=7 |pages=833–43 |date=July 2014 |pmid=24917215 |doi=10.1586/14737175.2014.928202 |url=}}</ref><ref name="pmid26189414">{{cite journal |vauthors=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 |title=Expert Consensus Group report on the use of apomorphine in the treatment of Parkinson's disease--Clinical practice recommendations |journal=Parkinsonism Relat. Disord. |volume=21 |issue=9 |pages=1023–30 |date=September 2015 |pmid=26189414 |doi=10.1016/j.parkreldis.2015.06.012 |url=}}</ref>
=== Neuroprotective treatments ===
=== Neuroprotective treatments ===
[[Neuroprotective]] treatments are at the forefront of PD research, but are still under clinical scrutiny<ref>{{cite journal| author=Bonuccelli U,
Neuroprotective drugs such as apoptotic drugs (CEP1347 and CTCT346), lazaroids, [[bioenergetics]] and antiglutamatergic agents.<ref>{{cite journal|year=2002|title=New drugs in the future treatment of Parkinson's disease|journal=J. Neurol.|volume=249 Suppl 2|issue=|pages=II30-5|doi=10.1007/s00415-002-1206-2|pmid=12375061|author=Djaldetti R, Melamed E}}</ref><ref>{{cite journal| author=Bonuccelli U,
Del Dotto P| title= New pharmacologic horizons in the treatment of Parkinson disease | journal=Neurology | year=2006 | volume=67 | issue=2 | pages= 30-38}}</ref>. 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<ref>{{cite journal |author=Djaldetti R, Melamed E |title=New drugs in the future treatment of Parkinson's disease |journal=J. Neurol. |volume=249 Suppl 2 |issue= |pages=II30-5 |year=2002 |pmid=12375061 |doi=10.1007/s00415-002-1206-2}}</ref>. Clinically evaluated neuroprotective agents are the monoamine oxidase inhibitors selegiline<ref name="PSG_1993">{{cite journal |author= |title=Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group |journal=N. Engl. J. Med. |volume=328 |issue=3 |pages=176-83 |year=1993 |pmid=8417384 |doi=}}</ref> and rasagiline, dopamine agonists, and the complex I mitochondrial fortifier coenzyme Q10.
Del Dotto P| title= New pharmacologic horizons in the treatment of Parkinson disease | journal=Neurology | year=2006 | volume=67 | issue=2 | pages= 30-38}}</ref>


=== Neural transplantation ===
=== 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.<ref>{{cite journal |author=Freed CR, Greene PE, Breeze RE, ''et al'' |title=Transplantation of embryonic dopamine neurons for severe Parkinson's disease |journal=N. Engl. J. Med. |volume=344 |issue=10 |pages=710-9 |year=2001 |pmid=11236774 |doi=}}</ref> A significant problem was the excess release of dopamine by the transplanted tissue, leading to [[dystonia]]s.<ref>{{cite journal |author=Redmond DE |title=Cellular replacement therapy for Parkinson's disease--where we are today? |journal=The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry |volume=8 |issue=5 |pages=457-88 |year=2002 |pmid=12374430 |doi=}}</ref> Research in African green monkeys suggests that the use of [[stem cell]]s might in future provide a similar benefit without inducing dystonias.<ref>{{cite journal |author=Redmond E et al |title=Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells |journal=Procedings of the National Academy of Sciences |volume=104 |issue=29 |year=2007}}</ref>
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 [[Parkinson's disease|PD]] patients under 60.<ref>{{cite journal |author=Freed CR, Greene PE, Breeze RE, ''et al'' |title=Transplantation of embryonic dopamine neurons for severe Parkinson's disease |journal=N. Engl. J. Med. |volume=344 |issue=10 |pages=710-9 |year=2001 |pmid=11236774 |doi=}}</ref> One of the [[side effects]] of this therapy is that it can cause [[dystonia]] by increased amount of [[dopamine]].<ref>{{cite journal |author=Redmond DE |title=Cellular replacement therapy for Parkinson's disease--where we are today? |journal=The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry |volume=8 |issue=5 |pages=457-88 |year=2002 |pmid=12374430 |doi=}}</ref> To solve this [[side effect]] a study in African monkeys suggest using [[stem cells]].<ref>{{cite journal |author=Redmond E et al |title=Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells |journal=Procedings of the National Academy of Sciences |volume=104 |issue=29 |year=2007}}</ref>


=== Nutrients ===
=== 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.<ref>{{cite journal | author=Lemoine P, Robelin N, Sebert P, Mouret J | title=La L-tyrosine : traitement au long cours de la maladie de Parkinson [L-tyrosine : A long term treatment of Parkinson's Disease] | journal=Comptes rendus academie des sciences | year=1986 | volume=309 | issue= | pages=43-47 | language=French }}</ref> 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.<ref>{{cite journal |author=Birkmayer W, Birkmayer JG |title=Iron, a new aid in the treatment of Parkinson patients |journal=J. Neural Transm. |volume=67 |issue=3-4 |pages=287-92 |year=1986 |pmid=3806082 | url=http://www.springerlink.com/link.asp?id=tp15r2g8u6327731}}</ref>
Nutrients can be very useful in controlling [[Parkinson's disease|PD]] [[symptoms]]. [[L-tyrosine]], the precursor of [[L-dopa]] is one of these nutrients.<ref>{{cite journal | author=Lemoine P, Robelin N, Sebert P, Mouret J | title=La L-tyrosine : traitement au long cours de la maladie de Parkinson [L-tyrosine : A long term treatment of Parkinson's Disease] | journal=Comptes rendus academie des sciences | year=1986 | volume=309 | issue= | pages=43-47 | language=French }}</ref> The other nutrient is ferrous iron which is the essential co factor for [[L-dopa]] biosynthesis.<ref>{{cite journal |author=Birkmayer W, Birkmayer JG |title=Iron, a new aid in the treatment of Parkinson patients |journal=J. Neural Transm. |volume=67 |issue=3-4 |pages=287-92 |year=1986 |pmid=3806082 | url=http://www.springerlink.com/link.asp?id=tp15r2g8u6327731}}</ref><ref>{{cite book | editor= Editors Przuntek H , Riederer P | title=Early diagnosis and preventive therapy in Parkinson's disease | date=1989 | publisher= Springer | isbn = 0-387-82080-9 | pages=p. 323}}</ref>  
<ref>{{cite book | editor= Editors Przuntek H , Riederer P | title=Early diagnosis and preventive therapy in Parkinson's disease | date=1989 | publisher= Springer | isbn = 0-387-82080-9 | pages=p. 323}}</ref>  
 
More limited efficacy has been obtained with the use of THFA, NADH, and pyridoxine—coenzymes and coenzyme precursors involved in dopamine biosynthesis.<ref>{{cite web | url = http://home.uchicago.edu/~syin/Kang.doc | title = Dopamine biosynthesis | accessdate = 2006-11-04 | format = Word doc | publisher = University of Chicago Personal Web Pages}}</ref> 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.<ref name="PSG_1993" />
 
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===
Other nutrients includes THFA, [[NADH]] and [[pyridoxine]]_ [[Coenzyme|coenzymes]], [[Coenzyme|coenzymes]] precursors<ref>{{cite web | url = http://home.uchicago.edu/~syin/Kang.doc | title = Dopamine biosynthesis | accessdate = 2006-11-04 | format = Word doc | publisher = University of Chicago Personal Web Pages}}</ref>, [[vitamin C]] and [[vitamin E]] in large doses. These [[Vitamin|vitamins]] are necessary for some enzymes such as [[superoxide dismutase]] and [[catalase]] to nullify the superoxide anions in damaged cells.<ref name="PSG_1993">{{cite journal |author= |title=Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. The Parkinson Study Group |journal=N. Engl. J. Med. |volume=328 |issue=3 |pages=176-83 |year=1993 |pmid=8417384 |doi=}}</ref>
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.<ref>{{cite journal | author = Schmitz-Hubsch T | title = Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study. | journal = Mov Disord | volume = 21 | issue = 4 | pages = 543-548 | year = 2006 | pmid = 16229022}}</ref>
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.<ref>{{cite journal |author=Burini D, Farabollini B, Iacucci S, ''et al'' |title=A randomised controlled cross-over trial of aerobic training versus Qigong in advanced Parkinson's disease |journal=Europa medicophysica |volume=42 |issue=3 |pages=231-8 |year=2006 |pmid=17039221 |doi=}}</ref>


===Exercise===
In one of the studies it was suggested that qigong exercise can improve [[Parkinson's disease|PD]] patient’s [[Symptom|symptoms]] by visualizing the flow of energy<ref>{{cite journal | author = Schmitz-Hubsch T | title = Qigong exercise for the symptoms of Parkinson's disease: a randomized, controlled pilot study. | journal = Mov Disord | volume = 21 | issue = 4 | pages = 543-548 | year = 2006 | pmid = 16229022}}</ref> But in another study there were evidences showing that [[aerobic exercise]] in beneficial for [[symptom]] control in [[Parkinson's disease|PD]] patients.<ref>{{cite journal |author=Burini D, Farabollini B, Iacucci S, ''et al'' |title=A randomised controlled cross-over trial of aerobic training versus Qigong in advanced Parkinson's disease |journal=Europa medicophysica |volume=42 |issue=3 |pages=231-8 |year=2006 |pmid=17039221 |doi=}}</ref>
===Botox===
===Botox===
Recently, [[Botox]] injections are being investigated as a non-FDA approved possible experimental treatment.<ref>{{Citeref patent | US | 6306403 }}</ref>
[[Botox]] injections are under investigation for treatment of [[Parkinson's disease|PD]] [[Symptom|symptoms]].<ref>{{Citeref patent | US | 6306403 }}</ref>


==References==
==References==

Latest revision as of 18:54, 23 April 2018

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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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