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rick--know of any other naturally occurring "prenylflavanones?")

Taiwan) NatureWise announces updates on cancer drug candidate, neurotrophic factors for neurodegenerative disorders


(Press release, NatureWise Biotech & Medicals Corp.)

6 June, 2008
Botanically-derived drug discovery and development firm NatureWise Biotech & Medicals Corp. (TPO:4732) announced this week two major updates to its drug discovery and development pipeline, with research results to be presented at the BIO 2008 conference and exhibition in San Diego 17-19 June, 2008.

The first is a drug candidate for targeted cancer therapy and spinal muscular atrophy (SMA), a genetic disorder. The second relates to the company's breakthrough neurotrophic factors derived from prenylflavanone agents (PPLs), which, unlike conventional neurotrophic factors, can pass the blood-brain barrier and reach neurons in the brain. This has exciting implications for the development of new drugs for neurodegenerative diseases, such as Alzheimer's disease.

The company will be making poster presentations at the BIO 2008 Innovation Corridor, a component of the 17-19 June international life science convention showcasing the latest advances in biotechnology research.

President of NatureWise, Dr. CY Huang, spoke of the upcoming presentation. "We're very exciting about the opportunity to present our findings at such an esteemed event and in front of such an important gathering of the international biotechnology and pharmaceutical community. We also look forward to soon announcing positive news from a clinical trial currently underway in Taiwan, comparing our PPLs with donepezil HCl therapy in patients with mild to moderate Alzheimer's disease," said Huang.

Regarding its plans, the company is looking to out-license its neural stem cell activity enhancement technologies. "We're also seeking partners willing to join us for further development into this exciting field of research," mentioned Huang.

NatureWise is also offering OEM or contract manufacturing in the areas of health foods or Traditional Chinese Medicine (TCM) products. Please visit NatureWise in San Diego at BIO 2008, booth 2501 in the exhibition hall, part of the Taiwan Pavilion.

About NBM-HD-1: Brain cancer and SMA therapy drug candidate:
NBM-HD-1 is NatureWise's cancer drug candidate, a new histone deacetylase (HDAC) inhibitor semi-synthesized from a natural compound with small molecule. Treating a range cancer cell lines (brain, colon, lung, liver, and breast) with NBM-HD-1 resulted in a significant increase of acetylated tubulin, histone H3 and H4 , and P21 waf1/cip levels in a dose- and time- dependent manner. The in vivo study of HD-1 on mice with xenografted glioma showed a significant reduction in tumor sizes compared with those of control group.

Research has also shown that the compound can pass the blood-brain barrier. Fifteen minutes after administering a single dose of 10 mg/kg NBM-HD-1 by IV, 25 percent of the compound could be measured in the brain cells. These results suggest that NBM-HD-1 has promising potential to become a drug to treat brain cancer. Moreover, many HDAC inhibitors were reported to be quality candidates for the treatment of spinal muscular atrophy (SMA).

About neurotrophic agents from PPLs for neurodegenerative disease therapy:
Several prenylflavanone compounds of small molecular weight--abbreviated as PPLs--were isolated from Taiwanese bee propolis. At low concentrations (as low as 150 ng/mL), these PPLs increased both the survival of cortical neurons and the proliferation of neural stem cells, and induced differentiation of neural stem cells into large number of neuronal cells. They were also found in rat astrocyte cells to significantly up-regulate gene expression of neurotrophic factors, such as GDNF and BDNF. These results suggest that PPLs play an important role as neurotrophic agents to enhance the survival, differentiation and function of neural stem cells. Furthermore, PPLs have been found capable of greatly enhancing the outgrowth of neurites.

About NatureWise Biotech & Medicals Corp:
Founded in 2000, Taipei, Taiwan-based NatureWise Biotech & Medicals Corp. is a botanically-derived drug discovery/development and health product company. The company's LipoCol Forte, a product for the treatment of (hypercholesterolemia and hypertriglyceridemia), was the first product in Taiwan to receive a 'New Drug Certificate of New Chinese Medicine' issued by Taiwan's Department of Health. It is the first TCM drug in Taiwan to complete Phase III trials in accordance with GCP guidelines, LipoCol Forte can be prescribed by doctors of Western medicine as well as TCM doctors. In addition, NatureWise also markets a range of dietary supplements and herbal products, including IQBLESS for memory enhancement.

Contact:
Email: jenny.jang@naturewise.com.tw
URL: www.naturewise.com.tw

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http://tinyurl.com/577ph7
The Patent Description & Claims data below is from USPTO Patent Application 20070232534.
Brief Patent Description - Full Patent Description - Patent Application Claims

BACKGROUND OF THE INVENTION

[0001] 1. Field of the Invention

[0002] The present invention relates to a compound for promoting regeneration and differentiation of neural stem cells.

[0003] 2. The Prior Arts

[0004] Neural stem cells (NSCs) are characterized as undifferentiated cells that have the capacity to self-renew and differentiate into other neural cells such as neurons, astrocytes and oligodendrocytes. NSCs can renew and differentiate in the presence of stimulating factors under in vitro cultural conditions. These differentiated cells play important roles during the development of central nervous system in mammals and also in the function of the fully developed nervous system in animals. NSCs can be isolated from the cortex of the brain of many mammals (such as mice, rats, pigs and humans) during their development before maturation. The NSCs in the central nervous system of humans are similar to those of rodents.

[0005] NSCs in mammals are present in mature organs as well as in the developing central nervous system. At the moment, one can also isolate neural stem cells from the embryonic brain of mammals; however, little is known on the mechanism of regulating endogenous neural stem cells.

[0006] The best method of treating a neurodegenerative disease is to restore and regenerate damaged or lost neural cells. Treatments in progress include replacing damaged cells through NSCs transplantation or activating endogenous NSCs in dormancy to "self-renew".

[0007] Although scientists have some knowledge of using NSCs to restore damaged neural cells, they need to find a way to effectively control them as they grow and differentiate into function-defined cells. Previous reports indicate that NSCs could propagate in a medium supplemented with growth factors such as basic Fibroblast Growth Factor (bFGF), Epithelial Growth Factor (EGF), etc. It is also known that in the presence of these growth factors in a serum-free medium, NSCs grown in suspension have the propensity to aggregate and form so-called "neurospheres". In addition, if these growth factors are removed and subsequently replaced with proper amount of known mitogenic factors, growth factors other than bFGF and EGF, or other neurotrophic factors, NSCs would most likely be stimulated into differentiation. The majority of the differentiated cells would be astrocytes (>90%), and only a few of them are neurons (<10%).

[0008] Many neurotrophic factors have been discovered in the past: Glial-derived Neurotrophic Factor (GDNF), Brain-derived Neurotrophic Factor (BDNF), Nerve Growth Factor (NGF), Neurotrophin-3 (NT3), Neurotrophin-4 (NT4), Platelet-derived Growth Factor (PDGF), and so on. Although these neurotrophic factors have been proven to promote the survival of neural cells, their clinical applications are limited. One reason is that their large molecular size prohibits them from passing the blood brain barrier (BBB).

[0009] If small molecular compounds could be found with the capability to activate endogenous NSCs, promote their growth and maintain their specificity, or even promote their differentiation into function able neurons, effective treatment or prevention of neurodegenerative diseases might become feasible. Through the effect of these compounds the success rate of NSCs transplantation into subjects may be improved.

SUMMARY OF THE INVENTION

[0010] To overcome the shortcomings of the prior art, the primary objective of the present invention is to provide a compound for promoting the growth of cortical neurons and NSCs, which has a small molecular size capable of passing blood brain barrier and reaching the brain more easily than large neurotrophic factors, to increase the survival rate of neural cells.

[0011] Another objective of the present invention is to provide a compound for promoting the differentiation of NSCs into neurons with specific functions.

[0012] To approach the above objectives, the present invention provides a prenylflavanone compound represented by a general formula as (I) shown below: wherein, R.sub.1 represents --H, --OH, a linear or branched alkyl group with 1 to 3 carbon atoms, or an isoprene group; R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6 and R.sub.7 represent --H, --OH, a linear or branched alkyl group with 1 to 3 carbon atoms, an isoprene group or a geranyl group represented by formula (II) or formula (III), respectively.

[0013] Cortical neurons cultured at low density (<160 cells/mm.sup.2) are known to die more frequently than those cultured at higher densities. The compound of the present invention not only increases the survival rate of cortical neurons, but also significantly decreases the death rate of cells in low-density cultures. The compound of the present invention can be used to promote the growth of cortical neurons, as evidenced by the thickness and length of their neurites. In addition, the compound of the present invention can also be used to promote the formation of NSCs and induce them to differentiate into neurons.

[0014] The present invention is further explained in the following embodiments. .....

[lou_lou]

THANK YOU!



Mitrochondrial research -
link
http://www.mitochondrial.net/showcit...europrotective