Gunstig effect van Uridine bij neuropathie
Uridine is een simpel molecuul, dat een boeiende werkzaamheid bezit in diermodellen, en hoogst waarschijnlijk ook bij mensen een zinvolle bijdrage kan leveren bij diabetische neuropathie.
Uridine is een essentieel molecuul voor de opbouw van RNA, de blueprint voor eiwitten en ontstaan uit het DNA. Er bestaat een Europees patent voor de inzet van uridine bij diabetische complicaties: European Patent EP0462075.
In 2009 beschreven onderzoekers dat de neuropathie die ontstond door de anti-AIDS middelen Zidovudine en zalcitabine, en die veroorzaakt wordt door afwijkingen in de energiecentrales van de cel, de mitochondria, tegengegaan kon worden door uridine.[1][2]
Diverse positieve effecten aangetoond
Ook de mitochondriale myopathie kan door uridine verminderd worden.[3]Ook kan uridine andere bijwerkingen van deze virusremmers tegengaan, zoals uitputting van mitochondriaal DNA, vervetting en verhoogde lactaatconcentraties in levercellen.[4]
Meerdere laboratoriumstudies hebben deze positieve effecten van uridine onderzocht bij vergiftiging van cellen door anti-AIDS middelen.[5][6] In een studie bij HIV patiënten werd duidelijk dat uridine een positieve invloed had op levercellen.[7]
En in een dubbelblinde studie bij diabetes patienten bleek uridine de geleiding van de zenuwen te verbeteren.[8] Daar gingen wel eerst enkele maanden overheen, zoals bij alle patogenetisch gerichte behandelingen:
- In the drug group, the neurophysiological parameters improved significantly from the 120th day post therapy compared with baseline and were maintained through to follow up.
Boeiend is dat de stof ook helpt bij droge ogen.[9] Uridine wordt ook geassocieerd met de regulatie van het hart- en vaatstelsel, het voortplantingssysteem en de organen met betrekking tot de ademhaling.[10] Ook bij AIDS wordt het middel als zinvol genoemd.[11][12][7]
Alleen. uridine is alleen als chemisch middel te krijgen en is bijzonder duur. Het is dus echt een ‘last resort’ middel. En verder is er eigenlijk alleen maar een goede studie bij mensen gedaan, en die is vrij oud en klein.
Er is ook een patent op het gebruik van uridine bij neuropathie, berustend o.a. op het artikel dat we hierboven beschreven. We geven de kern hier weer:
Patent voor uridine bij diabetes neuropathie
If the endocellular glucose exceeds the energy requirement, and is not stored in the form of polysaccharides, it can damage the cell, both because it changes into fructose and sorbitol (sugars which do not easily spread outwards, and which for this reason cause the cell to swell and lose functional activity), and because it can react with proteins and nucleic acids, bringing about a form of premature “cell aging”.
To relieve the peripheral symptomatology of diabetes mellitus, certain drugs have recently been proposed in the field of therapy. These drugs, by inhibiting the enzyme “aldosoreductase”, prevent the glucose from transforming itself into sorbitol, thus limiting the damage caused by cellular oedema (see for example Annual Reports in Medicinal Chemistry 19, 169-177, 1984). At least in short-term clinical tests, these compounds have shown themselves to be of use to antagonize diabetic neuropathies (see for example: Lancet II, 758-762, 1983; New England J. Medicine 316, 599-606, 1987).
However, these synthetic derivatives are not without side-effects which could compromise their long-term use, as in theory the diabetic patiënt would have to be treated all his life. It is therefore necessary to find physiological compounds that, as well as being active, are also free from serious undesirable effects.
It has now been surprisingly found, and forms the object of the present invention, that uridine possesses these properties and can be used to decrease the peripheral symptomatology of diabetes, without causing side-effects even in the case of long-term treatment. Uridine can thus be administered to patients suffering from diabetes mellitus for the pharmacological treatment of peripheral complications such as neuropathy, retinopathy or vasculopathy.
It is thought that the uridine, which is able to enter with ease into the cells, can store the glucose present therein under the form of glycogen.
Conclusie
Vervolgens werden de resultaten van de humane studie beschreven, die we hierboven citeerden. Als conclusie schrijven de patentschrijvers:
- The results reported above show that uridine is capable of reducing the entity of complications in diabetes mellitus in a group of patients treated for 6 months with the drug. The study was performed using a double-blind test and the results are derived from objective measures. It can thus be concluded that uridine, probably by means of the biosynthesis of glycogen within the cells, limits the damage caused by high levels of glucose, and can thus be used in the treatment of peripheral disturbances in diabetes, such as retinopathy, vasculopathy, etc.
The daily dose can vary between 500 and 2000 mg per day of uridine taken orally and the dose can be administered using the normal pharmaceutical forms.
December 2009: en David J Kopsky, artsen
Oorzaak Dunne Vezel Neuropathie (DVN)
Bekijk hier video’s van onze patiënten over pijnstillende crèmes.
[1] Venhoff N, Lebrecht D, Deveaud C, Beauvoit B, Bonnet J, Müller K, Kirschner J, Venhoff AC, Walker UA. | Oral uridine supplementation antagonizes the peripheral neuropathy and encephalopathy induced by antiretroviral nucleoside analogues. | AIDS. | 2010 Jan 28;24(3):345-52.
[2] Walker UA, Venhoff N, Koch EC, Olschewski M, Schneider J, Setzer B. | Uridine abrogates mitochondrial toxicity related to nucleoside analogue reverse transcriptase inhibitors in HepG2 cells. | Antivir Ther. | 2003 Oct;8(5):463-70.
[3] Lebrecht D, Deveaud C, Beauvoit B, Bonnet J, Kirschner J, Walker UA. | Uridine supplementation antagonizes zidovudine-induced mitochondrial myopathy and hyperlactatemia in mice. | Arthritis Rheum. | 2008 Jan;58(1):318-26.
[4] Walker UA, Venhoff N. | Uridine in the prevention and treatment of NRTI-related mitochondrial toxicity. | Antivir Ther. | 2005;10 Suppl 2:M117-23.
[5] Sommadossi JP, Carlisle R, Schinazi RF, Zhou Z. | Uridine reverses the toxicity of 3'-azido-3'-deoxythymidine in normal human granulocyte-macrophage progenitor cells in vitro without impairment of antiretroviral activity. | Antimicrob Agents Chemother. | 1988 Jul;32(7):997-1001.
[6] Keilbaugh SA, Hobbs GA, Simpson MV. | Anti-human immunodeficiency virus type 1 therapy and peripheral neuropathy: prevention of 2',3'-dideoxycytidine toxicity in PC12 cells, a neuronal model, by uridine and pyruvate. | Mol Pharmacol. | 1993 Oct;44(4):702-6.
[7] Banasch M, Goetze O, Knyhala K, Potthoff A, Schlottmann R, Kwiatek MA, Bulut K, Schmitz F, Schmidt WE, Brockmeyer NH. | Uridine supplementation enhances hepatic mitochondrial function in thymidine-analogue treated HIV-infected patients. | AIDS. | 2006 Jul 13;20(11):1554-6.
[8] Gallai V, Mazzotta G, Montesi S, Sarchielli P, Del Gatto F. | Effects of uridine in the treatment of diabetic neuropathy: an electrophysiological study. | Acta Neurol Scand. | 1992 Jul;86(1):3-7.
[9] Chang KC, Oh JY, In YS, Kim MK, Shin KC, Wee WR, Lee JH, Park MG. | Preliminary effects of oral uridine on the ocular surface in dry eye patients. | J Korean Med Sci. | 2009 Aug;24(4):701-7. Epub 2009 Jul 30.
[10] Pizzorno G, Cao D, Leffert JJ, Russell RL, Zhang D, Handschumacher RE. | Homeostatic control of uridine and the role of uridine phosphorylase: a biological and clinical update. | Biochim Biophys Acta. | 2002 Jul 18;1587(2-3):133-44.
[11] Di Biase DD. | Class II malocclusion: making the face fit? | Dent Update. | 1991 Dec;18(10):429-32, 434-5.
[12] McComsey GA, O'Riordan M, Setzer B, Lebrecht D, Baron E, Walker UA. | Uridine supplementation in HIV lipoatrophy: pilot trial on safety and effect on mitochondrial indices. | Eur J Clin Nutr. | 2008 Aug;62(8):1031-7. Epub 2007 May 30.
[13] Banasch M, Goetze O, Knyhala K, Potthoff A, Schlottmann R, Kwiatek MA, Bulut K, Schmitz F, Schmidt WE, Brockmeyer NH. | Uridine supplementation enhances hepatic mitochondrial function in thymidine-analogue treated HIV-infected patients. | AIDS. | 2006 Jul 13;20(11):1554-6.