Plant-based Parkingson’s drug Cogane enters clinical studies, says Phytopharm

Friday, February 12, 2010, 14:18 This news item was posted in Clinical Trials category and has 0 Comments so far.
http://www.dancewithshadows.com/pill...ys-phytopharm/

Phytopharm has also completed a Phase Ib stafety, tolerability and pharmacokinetic clinical study with Cogane, which was shown to be safe and generally well tolerated in both healthy volunteers and Parkinson’s disease patients over the twenty eight day study period.

When administered orally in several differenct preclinical models of Parkinson’s disease Cogane reverses the loss of dopaminergic neurones and elevates glial derived neurotrophic factor (GDNF)

GDNF has been shown to be particularly effective in re-growing damaged nerves. Since GDNF is a protein, it cannot be given orally (in tablet or liquid form) because it is degraded in the stomach and intestine, and also does not readily cross the blood-brain barrier.

that they will succede ...
and not end with yet another fiasco
Imad

1. Neuroreport. 1996 Sep 2;7(13):2171-5.

1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic
factor.

Naveilhan P, Neveu I, Wion D, Brachet P.

Institut National de la Santé et la Recherche Médicale, Centre Hospitalier
Universitaire, Angers, France.

Glial cell line-derived neurotrophic factor (GDNF) has significant therapeutic
potentials, in particular for neurodegenerative disorders. To determine factors
that would enhance GDNF expression, we analysed the effect of 1,25-(OH)2 D3 in C6
glioma cells. Treatment of C6 cells with 10(-7) M, 1,25-(OH)2 D3 for 48 h
elicited an 18.5-fold increase in the level of GDNF mRNA. In addition, our
results indicate that 1,25-(OH)2 D3 is effective at concentrations as low as
10(-10) M and that retinoic acid has additive effects. These data indicate that
1,25-(OH)2 D3 is a potent inducer of GDNF expression and suggest that 1,25-(OH)2
D3 may contribute to the regulation of GDNF in vivo.

PMID: 8930983 [PubMed - indexed for MEDLINE]


And more:


1: Sanchez B, Relova JL, Gallego R, Ben-Batalla I, Perez-Fernandez R.
1,25-Dihydroxyvitamin D3 administration to 6-hydroxydopamine-lesioned rats
increases glial cell line-derived neurotrophic factor and partially restores
tyrosine hydroxylase expression in substantia nigra and striatum. J Neurosci Res.
2009 Feb 15;87(3):723-32. PubMed PMID: 18816795.

2: Du F, Li R, Huang Y, Li X, Le W. Dopamine D3 receptor-preferring agonists
induce neurotrophic effects on mesencephalic dopamine neurons. Eur J Neurosci.
2005 Nov;22(10):2422-30. PubMed PMID: 16307585.

3: Lin AM, Chen KB, Chao PL. Antioxidative effect of vitamin D3 on zinc-induced
oxidative stress in CNS. Ann N Y Acad Sci. 2005 Aug;1053:319-29. PubMed PMID:
16179538.

4: Féron F, Burne TH, Brown J, Smith E, McGrath JJ, Mackay-Sim A, Eyles DW.
Developmental Vitamin D3 deficiency alters the adult rat brain. Brain Res Bull.
2005 Mar 15;65(2):141-8. PubMed PMID: 15763180.

5: Chen KB, Lin AM, Chiu TH. Systemic vitamin D3 attenuated oxidative injuries in
the locus coeruleus of rat brain. Ann N Y Acad Sci. 2003 May;993:313-24;
discussion 345-9. PubMed PMID: 12853323.

6: Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. Vitamin D3 and brain
development. Neuroscience. 2003;118(3):641-53. PubMed PMID: 12710973.

7: Sanchez B, Lopez-Martin E, Segura C, Labandeira-Garcia JL, Perez-Fernandez R.
1,25-Dihydroxyvitamin D(3) increases striatal GDNF mRNA and protein expression in
adult rats. Brain Res Mol Brain Res. 2002 Dec;108(1-2):143-6. PubMed PMID:
12480187.

8: Koyama Y. [Functional alterations of astroglia on brain pathologies and their
intracellular mechanisms]. Nippon Yakurigaku Zasshi. 2002 Mar;119(3):135-43.
Review. Japanese. PubMed PMID: 11915515.

9: Wang JY, Wu JN, Cherng TL, Hoffer BJ, Chen HH, Borlongan CV, Wang Y. Vitamin
D(3) attenuates 6-hydroxydopamine-induced neurotoxicity in rats. Brain Res. 2001
Jun 15;904(1):67-75. PubMed PMID: 11516412.

10: Rémy S, Naveilhan P, Brachet P, Neveu I. Differential regulation of GDNF,
neurturin, and their receptors in primary cultures of rat glial cells. J Neurosci
Res. 2001 May 1;64(3):242-51. PubMed PMID: 11319768.

11: Verity AN, Wyatt TL, Lee W, Hajos B, Baecker PA, Eglen RM, Johnson RM.
Differential regulation of glial cell line-derived neurotrophic factor (GDNF)
expression in human neuroblastoma and glioblastoma cell lines. J Neurosci Res.
1999 Jan 15;55(2):187-97. PubMed PMID: 9972821.

It may require high doses...


1. J Neurochem. 1985 Apr;44(4):1138-41.

Restricted transport of vitamin D and A derivatives through the rat blood-brain
barrier.

Pardridge WM, Sakiyama R, Coty WA.

The present studies measure the transport of retinol, retinoic acid,
1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], and 25-hydroxyvitamin D3 [25-(OH)D3]
through the rat brain capillary endothelial wall, i.e., the blood-brain barrier
(BBB). The vitamin A and D derivatives bind both to albumin and to specific
high-affinity binding proteins in plasma. In the presence of physiologic
concentrations of plasma proteins, the extraction by brain of all four compounds
was 5% or less.

PMID: 3838342 [PubMed - indexed for MEDLINE]

And according to the article: Phytopharm expects to start a Phase II study of Cogane with patients in the US in mid-2010 and then extend it into several other countries. Woo Hoo! Where do I sign up?? I will contact my neuro to see if this will be in trials in my community!

What is Cogane made from or is that a plant name that I am not familiar with?

the drug company is not releasing the name of the plant that Cogane comes from.

Thanks for this; I had suspected it was now protected under patent. If I am not mistaken, it is not the plant itself, but the neurotrophic GDNF that results in neuronal growth. The plant allows the neurotrophic to cross the blood brain barrier (much like the addition of Carbidopa) so we can take the treatment orally in pill form. Other pharmas researching GDNF like Ceregene are using viral vectors as a transit route to the brain.

Laura