Colchicine as a promising drug for Parkinson’s disease

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Correspondence / Medical Hypotheses 76 (2011) 144–151

[3] De Matteo R, May CN. Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide. Am J Physiol 1997;273:R1972–9. [4] Shimizu A, Yamada K, Meehan SM, Sachs DH, Colvin RB. Acceptance reaction: intragraft events associated with tolerance to renal allografts in miniature swine. J Am Soc Nephrol 2000;11:2371–80. [5] Alisky JM, Davidson BL. Towards therapy using RNA interference. Am J Pharmacogenomics 2004;4:45–51. [6] Chen S, Agarwal A, Glushakova OY, Jorgensen MS, Salgar S, et al. Gene delivery in renal tubular epithelial cells using recombinant adeno-associated viral vectors. J Am Soc Nephrol 2003;14:947–58. [7] Gusella GL, Fedorova E, Hanss B, Marras D, Klotman ME, Klotman PE. Lentiviral gene transduction of kidney. Hum Gene Ther 2002;13:407–14.

Joseph Martin Alisky Total Longterm Care Chambers Center, 3551 North Chambers Road, Suites A-D, Aurora, Colorado 80011, United States Tel.: +1 303 375 0649; fax: +1 303 375 9701 E-mail addresses: [email protected], [email protected]

10.1016/j.mehy.2010.10.018

Colchicine as a promising drug for Parkinson’s disease Sir, Parkinson’s disease (PD) is the most common neurodegenerative movement disorder, rising in incidence after the age of 60. The clinical motor dysfunction is primarily linked to the depletion of dopamine in the striatum, which is consecutive to the loss of the large dopaminergic neurons in the substantia nigra pars compacta (SNc). Despite the availability of effective symptomatic drugs, there is presently no cure for PD, and all attempts to slow the neuronal cell loss in the disease have failed [1]. The SNc homeostasis is vulnerable to different genetic, cellular and environmental factors that independently or concomitantly cause cell death over time. These factors may lead to inflammation [2], oxidative stress [3] and aberrant cell-cycle activation [4]. Colchicine is an alkaloid that has been used for centuries in acute gouty arthritis [5]. In the last decades it has been employed for an increasing number of diseases including familial Mediterranean fever (FMF), Behçet’s syndrome (BS), Sweet’s syndrome, scleroderma, amyloidosis and liver cirrhosis [6]. The therapeutic effect of Colchicine involves multiple inflammatory response pathways [6]. Its principal mechanism of action in Gout is thought to be inhibition of cytoskeletal microtubule polymerization, an effect – which is not only through its tubular inhibitory effects – but also due to changes at transcriptional levels by affecting genes regulating the cell cycle [6]. The second property of colchicine is its anti-oxidant effects through free radical scavenging [7]. The third capacity of colchicine is the anti-apoptotic effects coupled at the same time with anti mitotic effects [8], indicating that colchicine protects against death ligand-induced apoptosis by decreasing death-receptor targeting to the cell surface. These properties are related to the etiopathogenic mechanisms of PD. Recently, different clinical studies revealed that Gout is associated with a lower risk of PD [9,10]. Interestingly, individuals with Gout who received anti-gout treatment (normally treated with Colchicine) had a lower multivariate relative risk (0.66, 95% CI 0.54–0.81) than those who did not receive any anti-gout medication (0.79, 95% CI 0.59–1.05) [9].

All together, properties of Colchicine, related to the etiopathogenic mechanisms of PD, and the clinical evidence that anti-gout treatment lead to a lower risk of PD make Colchicine as a promising drug to treat PD. However, it should be noted that the experimental dose of colchicine is relatively high, and could have toxic effects in patients. Thus, the therapeutic dose in PD and its safety must be evaluated carefully. References [1] Obeso JA, Rodriguez-Oroz MC, Goetz CG, et al. Missing pieces in the Parkinson’s disease puzzle. Nat Med 2010;16:653–61. [2] Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell 2010;140:918–34. [3] Jenner P. Oxidative stress in Parkinson’s disease. Ann Neurol 2003;53(Suppl. 3):S26–36. discussion S36-28. [4] Hoglinger GU, Breunig JJ, Depboylu C, et al. The pRb/E2F cell-cycle pathway mediates cell death in Parkinson’s disease. Proc Natl Acad Sci USA 2007;104: 3585–90. [5] Richette P, Bardin T. Gout. Lancet 2010;375:318–28. [6] Ben-Chetrit E, Bergmann S, Sood R. Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis. Rheumatology (Oxford, England) 2006;45:274–82. [7] Modriansky M, Tyurina YY, Tyurin VA, et al. Anti-/pro-oxidant effects of phenolic compounds in cells: are colchicine metabolites chain-breaking antioxidants? Toxicology 2002;177:105–17. [8] Feng G, Kaplowitz N. Colchicine protects mice from the lethal effect of an agonistic anti-Fas antibody. J Clin Invest 2000;105:329–39. [9] De Vera M, Rahman MM, Rankin J, Kopec J, Gao X, Choi H. Gout and the risk of Parkinson’s disease: a cohort study. Arthritis Rheum 2008;59:1549–54. [10] Alonso A, Rodriguez LA, Logroscino G, Hernan MA. Gout and risk of Parkinson disease: a prospective study. Neurology 2007;69:1696–700.

Mohamed Salama Experimental Neurology, Phillips University, Marburg, Germany Oscar Arias-Carrión Experimental Neurology, Biomedical Research Center (BMFZ), Phillips University, Hans Meerwein Str., D-35043 Marburg, Germany E-mail address: [email protected]

10.1016/j.mehy.2010.10.032

Synchronized dance therapy to stimulate mirror neurons in autism Dear Editor, Autism is a disorder whose pathological basis is unknown. We postulate that one of the main deficits may be in the mirror neuron system. Neurons in the ventral premotor cortex in monkeys are known to fire when it makes a specific action such as

reaching for a peanut [1]. Some of these neurons (mirror neurons) also fire when the monkey merely watches another monkey perform the same movement; as if the neuron were performing a VR simulation of the other monkey’s impending action. This would be required for constructing a ‘‘theory of other minds” that is needed for social interactions. We proposed and provided the first experimental evidence for a dysfunctional MNS in ASD [2]. Subsequent research has confirmed these