Main menu
Select a language

Parkinson's Disease

There are approximately 6 million people with Parkinson’s disease worldwideANCHOR, although estimates range from 5-10 million. The symptoms include shaking, rigidity, balance problems and slowed movement. Parkinson’s disease is known to be caused by the death of brain cells that produce a certain neurotransmitter known as dopamine. These cells are in the substantia nigra, an area of the brain. The lack of dopamine affects the control of nerves responsible for movement. These symptoms appear once 70% of the cells have died, which makes early interventions highly important. Much of what we know about Parkinson's disease comes from models of the disease in animals, usually mice.

Dopamine and levodopa
Environmental factors
Genetic factors
Deep brain stimulation
Drug and dietary approaches
Stem cell research
Gene therapy

Dopamine and levodopa

Discovering the role of dopamine in the brain’s control of movement and its link to Parkinson’s disease was Nobel prize-winning work. Arvid Carlsson studied rabbits that had been given a drug that removes dopamine from their brain. He had hoped to see some effect on their movement, and indeed the rabbits went into complete stuporANCHOR. The rabbits’ movement could be restored by injecting them with levodopa (or L-dopa), a chemical that the brain converts into dopamineANCHOR.

When later studies by CarlssonANCHOR and others revealed that a lack of dopamine was the root cause of Parkinson’s disease, researchers could treat patients with levodopa just as they had with the rabbits.

Although levodopa helps some sufferers, its effects wear off over time. Research on rats indicated this is because the dopamine causes brain connections to become less responsive and therefore unable to process some signals. In 2002, research showed why: dopamine loss causes parts of the brain to reorganise and the brain becomes less able to process some signals. These are permanent changes that mean the condition will always be difficult to treat, shifting the emphasis to preventionANCHOR.

Another way to boost dopamine levels is taking drugs known as monoamine oxidase (MAO) inhibitors. There are currently two MAO inhibitors available: selegiline and rasagiline. They can be used in mild, early cases of Parkinson’s on their own and delay the need for L-DOPAANCHOR, or can be taken in combination with L-DOPA to improve symptoms and slow the development of dopamine resistanceANCHOR. Selegiline was the first MAO inhibitor to be used in this way, but in an attempt to avoid some of the neurotoxic side products of selegiline, researchers developed rasagilineANCHOR. Rasagiline was shown to increase dopamine levels in ratsANCHOR ANCHOR.

The video below shows how marmosets are used to study the effects of dopaminergic drugs:

Environmental factors

Parkinson’s symptoms can be induced by three chemicals: 6-OHDA, rotenone (a natural pesticide extracted from root vegetables), and MPTP, a common contaminant of street drugs. They may all lead to overproduction of nitric oxide, a naturally occurring chemical that is harmful in quantity. Genetically modified mice that cannot produce nitric oxide are resistant to the effects of MPTPANCHOR. Therefore, blocking nitric oxide production in the brains of people susceptible to Parkinson’s may prevent or slow the disease.

The effects of MPTP were discovered after several drug addicts appeared to develop Parkinson’s disease. It was traced back to an MPTP impurity in MPPP, a synthetic opioid drug. The MPTP was found to destroy the substantia nigra and killing dopamine-producing neurons. MPTP has since been used to develop animal models for Parkinson’s disease, particularly in mice and marmosets.

Rotenone, a potent pesticide, was first discovered to cause Parkinsonism in ratsANCHOR. In that study, the rats were injected with rotenone over 5 weeks and appeared to be a useful model for Parkinson’s disease. Further research in rats and cell cultures showed that prolonged exposure to rotenone could also trigger ParkinsonismANCHOR ANCHOR ANCHOR, and in 2011 a health study showed a link between Parkinson’s disease in farm workers and the use of rotenoneANCHOR.

Genetic factors

Though most cases are probably due to a combination of genes and environment, a small proportion of human disease is essentially genetic. Mice can be genetically programmed to simulate both the symptoms and the brain alterations found in Parkinson’s diseaseANCHOR ANCHOR.

Mutations in the protein LRRK2 are the most common cause of inheritable Parkinson’s disease. Although it accounts for only 2% of all cases of Parkinson’s in Western countries, this rises to 20% and 40% for Ashkenazi Jewish populations and North African Berber ancestry respectivelyANCHOR ANCHOR. Mutated forms of LRRK2 block the disposal of old, damaged proteins which then clump together in nerve cells and cause further damage.

A study has identified an important link between the two other inherited forms of the disease, in which the genes for either parkin or α-synuclein (αS) are mutated. We now know that both proteins interact with a third protein, synphilin, and the mutations disturb this interaction. Lewy bodies, found in patients’ brains and thought to be a cause of Parkinson’s, contain parkin, αS and synphilin. Researchers hope to reduce Lewy body formation by genetic engineeringANCHOR. β-synuclein inhibits αS in mice, and may in future be delivered to patients to reduce or prevent Parkinson’s diseaseANCHOR.

Deep brain simulation

Studies of monkeys led to understanding of the entire nerve circuitry involved in human Parkinson's disease. Part of the problem in Parkinson's disease is that the loss of dopamine in a region called the basal ganglia causes the output system to seize up  because other areas of the brain become too active. Switching off a specific part of the basal ganglia called the subthalamic nucleus can curb these effects. This is done by stimulating this brain area with tiny amounts of electrical current. A brain 'pacemaker', or Deep Brain Stimulation (DBS) of the subthalamic nucleus, reversed and improved the movements of monkeys with Parkinson’s diseaseANCHOR. This advance has proved effective on effective on human patientsANCHOR and was approved by the US Food and Drug Administration in January 2002. The benefits are often immediately apparent and quite dramatic. Over 80,000 patients worldwide have been treated with DBSANCHOR and the treatment is only available to patients whose symptoms cannot be controlled by drugs. In the video on the right, Mike Robbins demonstrates how deep brain stimulation helps him to control the symptoms of Parkinson's disease.

It is hoped that this treatment can be expanded to more patients by making the surgery less invasive. Recent research in mice and rats has shown that the DBS effect can be created by stimulating fibres in the spinal cordANCHOR. The technique, known as dorsal column stimulation, was first demonstrated in two different animal models of Parkinson’s disease – a genetically modified mouse and a chemically-induced rat model – and both showed marked improvement through the spinal stimulation. This has since been trialled in 18 Parkinson’s patients who have shown improvements in motor symptoms, gait and postureANCHOR ANCHOR ANCHOR ANCHOR.

There is even hope that surgery could be avoided altogether. Research in rats has suggested that the neurons activated by DBS are close to the surface of the brain, rather than at the site of the electrodeANCHOR. This means that these neurons could be reached by transcranial magnetic stimulation or similar techniques, where an electric field is created in the brain by applying a magnetic field outside the skull.

Drug and dietary approaches

Epidemiological studies on the population suggested that consuming caffeine reduces the risk of developing Parkinson’s diseaseANCHOR ANCHOR. This effect was further examined in a study of MPTP mouse models of Parkinson’s, which demonstrated that caffeine reduces the symptoms and works by blocking the A2A adenosine receptorANCHOR. There are now several A2A adenosine antagonists in clinical trials, and one known as Istradefylline has been approved for treating Parkinson’s in JapanANCHOR. In addition, a clinical trial of over 60 patients showed that a caffeine pill, equivalent to 3 cups of coffee a day, taken over 6 weeks, reduced tremors and improved mobilityANCHOR.

Research in mice suggests that a diet deficient in the B vitamin folic acid may raise the risk of Parkinson’s disease. The researchers recommend patients take 400 μg daily supplementsANCHOR. An epilepsy drug, D-beta-HB, restores impaired brain function in Parkinson’s mice and might therefore have a protective effective in humansANCHOR.

A modified tetracycline antibiotic called minocycline appears to prevent Parkinson-like brain cell loss in MPTP-treated mice. However, the antibiotic doesn’t enter the brain readily and the mice therefore needed high dosesANCHOR. Early clinical studies have shown that the drug does not have harmful effects, but further, larger trials will be needed to determine if it benefits neuroprotectionANCHOR.

Stem cell research

Stem cells are able to transform into different types of cells and it is hoped that they could be used to replace the lost dopamine-producing cells in patients with Parkinson's disease. Much of the initial research on these focused on using stem cells from embryos, as this was the most common source for them. This showed success in animal models of Parkinson's, with new nerve cells and dopamine-producing cells developing in the brainANCHOR ANCHOR ANCHOR ANCHOR ANCHOR ANCHOR. In one trial, monkeys given human embryonic stem cells showed dramatic improvement in their symptoms. Some were unable to move beforehand but were able to walk and feed themselves following treatmentANCHOR. Intriguingly, only a small proportion of the implanted cells became new dopamine-producing neurons while others became astrocytes – helper cells that help to support others and promote healing.

Since 2006, researchers have been able to transform specialised adult cells (often skin cells) so that they become like stem cells. These induced pluripotent stem (iPS) cells have provoked a great deal of research into this area. They are advantageous over embryonic stem cells as they avoid the ethical cost of harvesting from aborted foetuses and the iPS cells can be produced from the patients own cells, so they are a genetic match. However, further research is needed into iPS cells to better understand their limitations compared to true stem cells.

Research in monkeys has shown that iPS cells can be implanted into the brain without triggering an immune reaction, as long as the cells originally came from the recipientANCHOR. The scientists who carried out this research are now planning to start clinical trials in a small number of Parkinson’s patients in 2015ANCHOR.

Gene therapy

Gene therapy is technique for inserting genes into cells in order to either restore or boost function. This is viewed as a promising, yet difficult, approach for treating Parkinson's disease and there are currently two main approaches that have been takenANCHOR. The main approach is inserting genes that affect the activity of the neurons in the brain, by boosting production of dopamine or another neurotransmitter known as GABA (gamma-aminobutyric acid). An alternative technique is to try to repair the damaged cells or prevent further cells from becoming damaged.

The approach that progressed furthest is insertion of the GAD gene, which boosts GABA production. This was first demonstrated in rats in 2002ANCHOR and was followed by safety testing macaques ANCHOR ANCHOR, phase I clinical trialsANCHOR, and eventually double-blind phase II clinical trials in 2011ANCHOR. Although patients in the trial saw a 23% improvement on a standard test for Parkinson's symptoms, this was viewed as only a modest improvement and the program was discontinued by its sponsor NeurologixANCHOR.

An alternative approach is to insert genes that boost production of dopamine. The main target for this is the gene AADC, which is used to convert L-DOPA into dopamine. This approach was demonstrated in monkeys in 2000 ANCHOR before starting in clinical trials a few years later. This demonstrated that the technique was safeANCHOR ANCHOR, but there was only a modest improvement in symptomsANCHOR ANCHOR. This has been blamed on several factors including too low dosageANCHOR and a new clinical trial is due to be attemptedANCHOR.

AADC has also been used in combination with other genes known as TH and GTP-CH1, which together make up the main genes involved in dopamine production. Tests of this treatment showed good effectiveness in MPTP models of Parkinson’s in macaquesANCHOR. This was followed by a trial in 15 Parkinson’s disease patients, which showed modest improvements and no adverse effects related to the treatment ANCHOR. Like the AADC alone treatment, researchers are hoping to improve the method for delivering the virus into the brain before progressing to further trials.

Rather than attempting to boost dopamine production directly, researchers have also tried to boost repair and support the dopamine-producing cells by inserting the genes NRTN or GDNF.

There have so far been two phase II clinical trials for NRTN gene therapy, which aim to increase levels of the protein neuturinANCHOR ANCHOR ANCHOR. The first of these did not meet its targets by the end of the trial at 12 months, but seemed to show some success in patients who continued several months laterANCHOR. Following from research into animal modelsANCHOR ANCHOR, the trial was repeated with larger doses, refined targeting and longer time period. However, despite these changes the trial could not show benefit to the patients within statistical significanceANCHOR. It is still not clear why the results did not correlate between the animal studies and the clinical trials, but it does not appear to be due to insufficient dosageANCHOR ANCHOR. It has been suggested that Parkinson’s disease could prevent the neurturin protein from spreading throughout the damaged region, a problem that is not found in the animal modelsANCHOR ANCHOR ANCHOR.

There are trials for GDNF gene therapy, following the improvement of symptoms in monkeys through this techniqueANCHOR. However, the levels and distribution of GDNF in the body is similar to NRTN and so may face similar problems ANCHOR..


  1. Baker MG, Graham L (2004) ‘The journey: Parkinson’s disease.’ BMJ 329(7466):611-614 doi: 10.1136/bmj.329.7466.611
  2. Carlsson A et al (1957) Effect of reserpine on the metabolism of catecholamines In: Garattini S, Ghetti V, eds. Psychotropic Drugs. Amsterdam:Elsevier (363-372)
  3. Carlsson A, Lindqvist M, Magnusson T (1957) 3,4-Dihydroxyphenylaalanine and 5-hydroxytrramine in brain. Science 127:471
  4. Carlsson A (1959) The occurrence, distribution and physiological role of catecholamines in the nervious system. Pharmacol Rev 11:490-493
  5. Cho J, Duke D, Manzino L, et al (2002) Dopamine depletion causes fragmented clustering of neurons in the sensorimotor striatum: Evidence of lasting reorganization of corticostriatal input J Comp Neurol 452 24
  6. Riederer P, Lachenmayer L (2003) Selegiline's neuroprotective capacity revisited J Neural Transm 110(11):1273–8 doi: 10.1007/s00702003-0083-x.
  7. Ives NJ, Stowe RL, Marro J et al (2004) Monoamine oxidase type B inhibitors in early Parkinson's disease: meta-analysis of 17 randomised trials involving 3525 patients BMJ 329(7466):593 doi:10.1136/bmj.38184.606169.AE
  8. Tabakman R, Lecht S, Lazarovici P (2004) Neuroprotection by monoamine oxidase B inhibitors: a therapeutic strategy for Parkinson's disease? Bioessays 26(1):80–90 doi:10.1002/bies.10378
  9. Finberg, Tenne (1982) Relationship between tyramine potentiation and selective inhibition of monoamine oxidase types A and B in the rat vas deferens Brit J Pharm 77(1):13-21
  10. Lamensdorf I, Youdim MB, Finberg JP (1996) Effect of long-term treatment with selective monoamine oxidase A and B inhibitors on dopamine release from rat striatum in vivo J Neurochem 67(4):1532-9
  11. Liberatore G, Jackson-Lewis V, Vukosavic S et al (1999) Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson's disease Nature Med 5, 1403
  12. Betarbet R, Sherer TB, MacKenzie G et al (2001) Chronic systemic pesticide exposure reproduces features of Parkinson's disease Nature Neurosci 3, 1301
  13. Gao HM, Liu B, Hong JS (2003) Critical role for microglial NADPH oxidase in rotenone-induced degeneration of dopaminergic neurons The Journal of Neuroscience 23(15):6181–7
  14. Freestone PS et al (2009) Acute action of rotenone on nigral dopaminergic neurons--involvement of reactive oxygen species and disruption of Ca2+ homeostasis The European Journal of Neuroscience 30(10):1849–59 doi:10.1111/j.1460-9568.2009.06990.x
  15. Pan-Montojo F et al (2010) Progression of Parkinson's Disease Pathology Is Reproduced by Intragastric Administration of Rotenone in Mice In Kleinschnitz, Christoph. PLoS ONE 5(1):e8762 doi:10.1371/journal.pone.000876
  16. Tanner CM et al (2011) Rotenone, Paraquat and Parkinson’s Disease Environmental Health Perspectives 119(6):866–72 doi:10.1289/ehp.1002839
  17. Beal MF (2002) Experimental models of Parkinson's disease Nature Neurosci 2, 325
  18. Masliah E, Rockenstein E, Veinbergs I, et al (2000) Dopaminergic loss and inclusion body formation in alpha-synuclein mice: Implications for neurodegenerative disorders Science 278,1265
  19. 1Ozelius LJ et al (2006) LRRK2 G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews N Engl J Med 2006; 354:424-425 DOI: 10.1056/NEJMc055509
  20. Lesage S, Ibanez P, Lohmann E, et al (2005) G2019S LRRK2 mutation in French and North African families with Parkinson's disease. Ann Neurol 58:784-787
  21. Chung KKK, Zhang Y, Lim KL (2001) Parkin ubiquitinates the a-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease Nature Medicine 7, 1144
  22. Hashimoto M, Rockenstein E, Mante M (2001) ß-synuclein inhibits a-synuclein aggregation: a possible role as an anti-parkinsonian factor Neuron 32,  213
  23. Benazzouz A, Gross C, Feger J et al (1993) Reversal of rigidity and improvement of motor performance by subthalamic high-frequency stimulation in MPTP-treated monkeys Eur J Neurosci 5(4), 382
  24. Limousin P, Krack P, Pollak P et al (1998) Electrical stimulation of the subthalamic nucleus on advanced Parkinson's disease New Engl J Med 339, 1105
  26. Fuentes R et al (2009) Spinal Cord Stimulation Restores Locomotion in Animal Models of Parkinson's Disease Science 323, 1578–1582
  27. Fénelon G, Goujon C, Gurruchaga JM, Cesaro P, Jarraya B, Palfi S, Lefaucheur JP (2012) Spinal cord stimulation for chronic pain improved motor function in a patient with Parkinson's disease Parkinsonism Relat Disord. 18(2):213-4
  28. Agari T, Date I (2012) Spinal cord stimulation for the treatment of abnormal posture and gait disorder in patients with Parkinson's disease. Neurol Med Chir (Tokyo) 52(7):470-4.
  29. Landi A, Trezza A, Pirillo D, Vimercati A, Antonini A, Sganzerla EP (2013) Spinal cord stimulation for the treatment of sensory symptoms in advanced Parkinson's disease. Neuromodulation 16(3):276-9
  30. Hassan S, Amer S, Alwaki A, Elborno A (2013) A patient with Parkinson's disease benefits from spinal cord stimulation. J Clin Neurosci. 20(8):1155-6
  31. Gradinaru, V., Mogri, M., Thompson, K. R., Henderson, J. M. & Deisseroth, K. (2009) Science doi:10.1126/science.1167093
  32. Ross GW et al (2000) Association of coffee and caffeine intake with the risk of Parkinson disease. JAMA 283:2674–2679
  33. Benedetti MD et al (2000) Smoking, alcohol, and coffee consumption preceding Parkinson’s disease: a case-control study. Neurology 55:1350–1357
  34. Chen J-F, Xu K, Petzer JP et al (2001) Neuroprotection by caffeine and A2A adenosine receptor inactivation in a model of Parkinson's disease J Neurosci 21, RC143
  35. Dungo R, Deeks ED (2013) Istradefylline: first global approval Drugs 73(8):875-82 doi: 10.1007/s40265-013-0066-7
  36. Postuma, RB et al (2012) Caffeine for treatment of Parkinson disease Neurology 79(7):651-658
  37. Duan W, Ladenheim B, Cutler RG, et al (2002) Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease J Neurochem 2002 80, 101
  38. Tieu K, Perier C, Caspersen C et al (2003) D-ß-Hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease J. Clin. Invest. 112, 892.
  39. Du Y, Ma Z, Lin S (2001) Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson's disease Proc Nat Acad Sci 98, 14669
  40. JM Plane et al (2010) Prospects for Minocycline Neuroprotection Arch Neurol. 67(12):1442-1448. doi:10.1001/archneurol.2010.191
  41. Flax JD, Aurora S, Yang C et al (1998) Engraftable human neural stem cells respond to development clues, replace neurons, and express foreign genes Nature Biotechnology 16, 1033
  42. Yandava BD, Billinghurst LL & Snyder EY (1999) "Global" cell replacement is feasible via neural stem cell transplantation: Evidence from the dysmyelinated shiverer mouse brain Proc Nat Acad Sci 96, 7029
  43. Wagner J, Akerud P, Castro DS, Holm PC, Canals JM, Snyder EY, Perlmann T, Arenas E (1999) Induction of a midbrain dopaminergic phenotype in Nurr1-overexpressing neural stem cells by type 1 astrocytes Nature Biotechnology 7, 653
  44. Rietze RL, Valcanis H, Brooker GF et al (2002) Purification of a pluripotent neural stem cell from the adult mouse brain Nature 412, 736
  45. Björklund LM, Sánchez-Pernaute R, Chung S et al (2002) Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model Proc Nat Acad Sci 99, 2344
  46. Kawasaki H, Suemori H, Mizuseki K et al (2002) Generation of dopaminergic neurons and pigmented epithelia from primate ES cells by stromal cell-derived inducing activity Proc Nat Acad Sci 99, 1580
  47. Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0704091104
  48. Asuka Morizane et al (2013) Direct Comparison of Autologous and Allogeneic Transplantation of iPSC-Derived Neural Cells in the Brain of a Nonhuman Primate 1(4) p283–292 DOI:
  50. Bartus RT, Weinberg MS, Samulski RJ (2014) Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy 22(3):487–497 doi: 10.1038/mt.2013.281
  51. Luo J et al (2002) Subthalamic GAD gene therapy in a Parkinson's disease rat model Science 298(5592):425-9
  52. Emborg ME et al (2007) Subthalamic glutamic acid decarboxylase gene therapy: changes in motor function and cortical metabolism J Cereb Blood Flow Metab 27(3):501-9
  53. Luo J, Kaplitt MG, Fitzsimons HL et al (2002) GAD gene therapy in a Parkinson's disease rat model Science 298, 425
  54. Kaplitt MG et al(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
  55. LeWitt PA et al(2011) AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial Lancet Neurol 10(4):309-19 doi: 10.1016/S1474-4422(11)70039-4
  56. Bartus RT, Weinberg MS, Samulski RJ (2014) Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy 22(3):487–497 doi: 10.1038/mt.2013.281
  57. Bankiewicz KS, Eberling JL, Kohutnicka M, Jagust W, Pivirotto P, Bringas J, Cunningham J, Budinger TF, Harvey-White (2000) Convection-enhanced delivery of AAV vector in parkinsonian monkeys; in vivo detection of gene expression and restoration of dopaminergic function using pro-drug approach. J Exp Neurol. 164(1):2-14
  58. Mittermeyer G, Christine CW, Rosenbluth KH, Baker SL, Starr P, Larson P, Kaplan PL, Forsayeth J, Aminoff MJ, Bankiewicz KS (2012) Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease. Hum Gene Ther. 23(4):377-81
  59. Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, VanBrocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ (2009) Safety and tolerability of putaminal AADC gene therapy for Parkinson disease Neurology 73(20):1662-9
  60. Coune PG, Schneider BL, Aebischer P (2012) Review Parkinson's disease: gene therapies Cold Spring Harb Perspect Med. 2(4):a009431
  61. Bjorklund T, Kordower JH (2010) Review Gene therapy for Parkinson's disease. Mov Disord. 25 Suppl 1():S161-73
  62. Mittermeyer G, Christine CW, Rosenbluth KH, Baker SL, Starr P, Larson P, Kaplan PL, Forsayeth J, Aminoff MJ, Bankiewicz KS (2012) Long-term evaluation of a phase 1 study of AADC gene therapy for Parkinson's disease. Hum Gene Ther. 23(4):377-81
  63. Herpich N. (2013) Novel partnership between academia and industry drives forward gene therapy approach to treat Parkinson's. FoxFeed Blog:
  64. Jarraya B, Boulet S, Ralph GS, Jan C, Bonvento G, Azzouz M, Miskin JE, Shin M, Delzescaux T, Drouot X, Hérard AS, Day DM, Brouillet E, Kingsman SM, Hantraye P, Mitrophanous KA, Mazarakis ND, Palfi S (2009) Dopamine gene therapy for Parkinson's disease in a nonhuman primate without associated dyskinesia. Sci Transl Med. 1(2):2ra4 
  65. Bartus RT, Weinberg MS, Samulski RJ (2014) Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy 22(3):487–497 doi: 10.1038/mt.2013.281
  66. Marks WJ et al (2010) Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol. 9(12):1164-72
  67.  Bartus R. (2013) CERE-120 (AAV-neurturin) for the Treatment of Parkinson's Disease: Experience from 4 Clinical Trials and Human Autopsy Data.American Society of Gene and Cell Therapy 16th Annual Meeting: Salt Palace Convention Center in Salt Lake City, Utah, USA.
  68. Bartus RT et al (2013) Review Advancing neurotrophic factors as treatments for age-related neurodegenerative diseases: developing and demonstrating "clinical proof-of-concept" for AAV-neurturin (CERE-120) in Parkinson's disease. Neurobiol Aging. 34(1):35-61
  69. Bartus RT et al (2013) Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology 80(18):1698-701
  70. Bartus RT et al (2011) Properly scaled and targeted AAV2-NRTN (neurturin) to the substantia nigra is safe, effective and causes no weight loss: support for nigral targeting in Parkinson's disease Neurobiol Dis. 44(1):38-52
  71. Herzog CD et al (2013) Enhanced neurotrophic distribution, cell signaling and neuroprotection following substantia nigral versus striatal delivery of AAV2-NRTN (CERE-120). Neurobiol Dis. 58:38-48
  72. Bartus R. (2013) CERE-120 (AAV-neurturin) for the Treatment of Parkinson's Disease: Experience from 4 Clinical Trials and Human Autopsy Data.American Society of Gene and Cell Therapy 16th Annual Meeting: Salt Palace Convention Center in Salt Lake City, Utah, USA.
  73. Bartus RT et al (2013) Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology 80(18):1698-701
  74. Herzog CD et al (2012) Robust, stable, targeted, long-term neurturin expression and enhanced tyosine hyroxylase labeling in Parkinson's disease brain 4 years following delivery of CERE-120 (AAV2-neurturin) to the human putamen Society for Neuroscience; New Orleans, LA; 2012.
  75. Bartus RT et al (2013) Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology 80(18):1698-701
  76. Herzog CD et al (2012) Robust, stable, targeted, long-term neurturin expression and enhanced tyosine hyroxylase labeling in Parkinson's disease brain 4 years following delivery of CERE-120 (AAV2-neurturin) to the human putamen Society for Neuroscience; New Orleans, LA; 2012.
  77. Bartus RT et al (2011) Bioactivity of AAV2-neurturin gene therapy (CERE-120): differences between Parkinson's disease and nonhuman primate brains. Mov Disord. 26(1):27-36
  78. Kordower JH, Emborg ME, Bloch J et al (2000) Neurodegeneration prevented by lentiviral vector delivery of GDNF in primate models of Parkinson's disease Science 290, 767
  79. Bartus RT, Weinberg MS, Samulski RJ (2014) Parkinson's Disease Gene Therapy: Success by Design Meets Failure by Efficacy 22(3):487–497 doi: 10.1038/mt.2013.281
  80. Rosenblad C et al (1999) Protection and regeneration of nigral dopaminergic neurons by neurturin or GDNF in a partial lesion model of Parkinson's disease after administration into the striatum or the lateral ventricle. Eur J Neurosci. 11(5):1554-66

Last edited: 15 September 2014 08:09

Main menu
Select a language