Parkinson's Disease Tulip


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Old 08-09-2015, 09:59 PM #1
Tupelo3 Tupelo3 is offline
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Default Promising drug for PD supports fast track status

Promising drug for Parkinson's disease: Study supports fast track to clinical trials

A drug which has already been in use for decades to treat liver disease could be an effective treatment to slow down progression of Parkinson's disease, scientists from the University of Sheffield have discovered.

The pioneering research led by academics from the Sheffield Institute of Translational Neuroscience (SITraN), in collaboration with scientists from the University of York, supports the fast-tracking of the drug ursodeoxycholic acid (UDCA) for a clinical trial in Parkinson's patients.

http://www.eurekalert.org/pub_releas...-pdf080715.php
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Old 08-10-2015, 10:27 AM #2
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Would approval in UK affect US status?
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Old 08-22-2015, 07:49 PM #3
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Quote:
Originally Posted by badboy99 View Post
Would approval in UK affect US status?

http://www.ncbi.nlm.nih.gov/pubmed/24891994

Glob Adv Health Med. 2014 May; 3(3): 58–69.
Published online 2014 May 1. doi: 10.7453/gahmj.2014.017
PMCID: PMC4030606
The Unexpected Uses of Urso- and Tauroursodeoxycholic Acid in the Treatment of Non-liver Diseases

Sheila Vang, Katie Longley, Clifford J. Steer, MD,corresponding author and Walter C. Low, PhDcorresponding author

Abstract
Tauroursodeoxycholic acid (TUDCA) is the taurine conjugate of ursodeoxycholic acid (UDCA), a US Food and Drug Administration–approved hydrophilic bile acid for the treatment of certain cholestatic liver diseases. There is a growing body of research on the mechanism(s) of TUDCA and its potential therapeutic effect on a wide variety of non-liver diseases. Both UDCA and TUDCA are potent inhibitors of apoptosis, in part by interfering with the upstream mitochondrial pathway of cell death, inhibiting oxygen-radical production, reducing endoplasmic reticulum (ER) stress, and stabilizing the unfolded protein response (UPR). Several studies have demonstrated that TUDCA serves as an anti-apoptotic agent for a number of neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and Huntington's disease. In addition, TUDCA plays an important role in protecting against cell death in certain retinal disorders, such as retinitis pigmentosa. It has been shown to reduce ER stress associated with elevated glucose levels in diabetes by inhibiting caspase activation, up-regulating the UPR, and inhibiting reactive oxygen species. Obesity, stroke, acute myocardial infarction, spinal cord injury, and a long list of acute and chronic non-liver diseases associated with apoptosis are all potential therapeutic targets for T/UDCA. A growing number of pre-clinical and clinical studies underscore the potential benefit of this simple, naturally occurring bile acid, which has been used in Chinese medicine for more than 3000 years.

PARKINSON'S DISEASE
Parkinson's disease is a progressive neurodegenerative disease characterized by cardinal symptoms such as resting tremor, rigidity, postural instability, and brady-kinesia. It is caused by relentless loss of nigrostriatal dopaminergic neurons in the substantia nigra of the brain. There are many pathogenic mechanisms in PD, but one of the most common is a vicious cycle of oxidative damage and decrease in anti-oxidative glutathione in PD brain tissue.22 Signs of apoptosis include mitochondrial dysfunction, chromatin condensation, and caspase activation in dying cells. Mitochondrial dysfunction leads to downstream increase in reactive oxygen species (ROS), inflammatory responses, and activation of cell death pathways. Syndromes related to PD are caused by ingestion of complex I inhibitors. The complex I inhibitor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes degeneration of nigrostriatal dopaminergic neurons and characterizes a toxin paradigm for PD.23 Rotenone is another complex I inhibitor that causes multiple changes in the mitochondria relevant to PD. It is known to induce free radical generation, inhibition of complex I, and apoptosis.24 In the pathogenesis of PD, the JNK pathway constitutes a central stress activated response, and increased levels are found in PD brains.23 UDCA and TUDCA have been studied and found to play a role as a neuroprotectant in PD by protecting against apoptosis and regulating JNK activity and cellular redox thresholds.

A number of genes have been associated with familial cases of PD. Genetic modulation of α-synuclein, parkin, and DJ-1 all disrupt mitochondrial function in Caenorhabditis elegans. TUDCA treatment yielded protection against rotenone-induced toxicity. Non-tg lines were fully protected by TUDCA, and K08E3.7 and α-synuclein-expressing strains showed increased survival with TUDCA treatment. A gene associated with cell death that takes place during the development of the nematode C elegans is ced-3. TUDCA does not protect C elegans lacking ced-3, suggesting that TUDCA acts in part by inhibiting apoptosis.24

UDCA and its highly water-soluble formula, Yoo's solution (YS) were shown to protect the human dopaminergic neuronal cell line SH-SY5Y against sodium nitroprusside (SNP)–induced cytotoxicity.23 SNP was used as a neurotoxicant due to its strong NO-generating characteristics and cytotoxicity in dopaminergic cells. UDCA significantly attenuated programmed cell death processes such as nuclear fragmentation, caspase activation, MMP decrease, and cytochrome c release. ROS such as superoxide, hydrogen peroxide, hydroxyl radical, and RNS including NO directly contribute to oxidative damage of dopaminergic cells. UDCA decreased the generation of total ROS and NO. Glutathione (GSH), an endogenous tripeptide anti-oxidant, exerts critical protective effects as a representative intracellular anti-oxidant. Under normal conditions, GSH is properly maintained in most cells and suppresses the spontaneous oxidative damage induced by PD-related toxicants. UDCA maintained the GSH level under oxidative stress caused by SNP.23

The neuroprotective role of TUDCA against MPTP toxicity was observed in a study with mice lacking glutathione S-transferase pi (GSTP), an endogenous JNK inhibitor. Pre-treatment with TUDCA significantly reduced the depletion of DA neurons and dopaminergic fiber loss caused by MPTP. TUDCA protected against MPTP-induced neurodegeneration by delaying and decreasing dopaminergic cell loss. Pre-treatment with TUDCA modified the cellular environment and attenuated the deleterious events of MPTP by blocking ROS production and JNK activation in GSTP null mice.23

TUDCA administration is also neuroprotective for nigral dopamine neurons transplanted into rodent models of PD. Numerous studies have demonstrated that the transplantation of fetal nigral dopamine neurons results in a 90% to 95% loss of transplanted neurons because of apoptosis. Parkinsonian rats were transplanted with nigral dopamine neurons from fetal rats incubated in 50 uM TUDCA or saline. Rats treated with dopamine neurons incubated in TUDCA exhibited a significant reduction in rotational asymmetry compared to rats transplanted with dopamine neurons alone.25 Histological analysis of the transplanted cells revealed a significantly greater number of tyrosine-positive cells that survived transplantation in the TUDCA-treated cells vs the saline-treated cells. Incubation of isolated dopamine neurons with TUDCA resulted in significantly fewer TUNEL-positive neurons in comparison with vehicle controls. Together, these results suggested that TUDCA can enhance survival of transplanted dopamine neurons via reduction of apoptosis. Interestingly, a recent study that screened more than 2000 compounds identified ursocholanic acid and its chemically-related compound UDCA as highly promising drug therapies for future neuroprotective trials in PD.26

Last edited by wxxu; 08-23-2015 at 12:28 PM.
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Old 08-22-2015, 10:17 PM #4
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Default Otc?

Anyone know if you can get this online/OTC? And if so, dose?
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Old 08-23-2015, 09:02 AM #5
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US Versions: Actigall and Urso

http://www.drugs.com/cdi/actigall.html

http://www.rxlist.com/urso-drug.htm

US Generic version: ursodiol

http://www.drugs.com/cdi/ursodiol.html


http://www.drugs.com/pro/ursodiol-capsules.html
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Old 08-23-2015, 12:36 PM #6
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TUDCA is available at
http://www.amazon.com/s/ref=nb_sb_no...es%2Ck%3Atudca
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Old 08-25-2015, 11:32 AM #7
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Anyone taking TUDCA that wishes to share about your experience?
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