CHECK THIS site www.medicalnewstoday.com/medicalnews.php?newsid=9001

[gmebius]

http://www.medicalnewstoday.com/medical ... ewsid=9001

Please advise if you have heard of this before!

I have an injury since 1992 and have basically no motion in right arm! exept for a bit in biceps and triceps.

[ptrefam]

Doesn't sound like they are trying it on humans yet? I see all this wonderful research and anxiously await the time for human trials. I would love to put Dustin in the line.
Sue

[cbe411]

This is the first I have heard of this too... but it does sound great!!

Hell I would VERY WILLINGLY put myself out there through this stuff, what have I got to lose?

Christopher... do you have any knowledge of this? You are great with networking and research!!

Thanks for posting this link...

Courtney

[Fernando]

Hi Gunnar

What part of Mexico do you live in?

Saludos
Fernando

[Christopher]

Yeah, I missed this one, surprised me too. Looks like a promising different approach from anything I've read of before.

The place where I usually find most of the recent research on nerve and spinal injuries does have discussion on it and it's researchers. I'll post it below.




This commentary is written by Dr. Wise Young, one of the worlds foremost Spinal Cord Injury researchers and founder of the site where I got this from...

a search on INNUREX brings up more posts on this research
--------------------------
http://sci.rutgers.edu/forum/showthread.php?t=22054

06-05-2005, 03:04 AM
Wise Young
Administrator
New Brunswick, NJ, USA


I want to emphasize that this is just an abstract being presented at a meeting and we need to look at the data very carefully before jumping to the conclusion that this is regenerating the spinal cord. Of course, it is very interesting and we should be paying close attention to this treatment. What do we know about RAR2, lentiviral gene delivery, and what the company has done?

What is Innurex? It is apparently a gene therapy that introduces the gene RAR2 using a lentivirus. What is RAR2? It is a subtype of the retinoic acid receptor. Estrogen stimulates the expression of retinoic acid receptors (RAR-alpha-1). These receptors regulate differentiation of cells, particularly of stem cells during development. Retinoic acid receptors are nuclear receptors that are related to steroid and thyroid hormone receptors (http://www.iephb.nw.ru/labs/lab38/sp...x_pro/rar.html). A number of RAR receptor subtypes and genes have been identified: alpha, beta, and gamma. The RAR2 gene apparently refers to RAR-alpha-2. Presumably, what this treatment does is to get certain cells to express the RAR2 gene, which may or may not result in the expression of the RAR2 receptor.

What is retinoic acid? Retinoic acid has been used for years in cosmetic and skin care products. Retinoic acid stimulates differentiation of cells. Many studies have shown that retinoic acid receptors play an important role in differentiation of stem cells and other cells into neurons. For example, we often apply retinoic acid to stem cell cultures to try to get them to produce more neurons and glia. (See Zechel, 2005 abstract below) There is a great deal of interest in the use of retinoic acid or gene therapies involving retinoic acid receptors to treat tumors, including breast cancer and leukemia (see Chen, et al., 2005 abstract below).

Lentivirus is a type of retrovirus that can infect both dividing and non-dividing cells, inserting genes into the cells. The genes are often expressed in the target cell for up to 6 months. They are known to infect neurons, macrophages, hematopoietic stem cells, muscle, and liver cells, cells that have been relatively resistant to other viral infections. Lentiviruses do not transfect quiescent cells. Please note that lentivirus is a type of virus that includes the HIV (AIDS) virus. http://biology.kenyon.edu/slonc/gene.../Lentivi2.html

The company Oxford Biomedica paid £180,000 to King's College at Oxford to license this gene that was discovered by Professor Malcolm Maden. Alan King is the chief executive of Oxford Biomedica. The company has two products in clinical trials: MetXia for breast and ovarian cancer and TroVax for colorectal cancer. http://www.guardian.co.uk/genes/arti...433482,00.html

What are the possibilities of Innurex going to clinical trial for spinal cord injury? The gene therapy field has gone through many ups and downs over the past decade. A number of viral systems (adenovirus, retrovirus) have been used in clinical trial. Several have been stopped or slowed down due to complications. For example, the Jesse Gelsinger case essentially stopped or delayed adenovirus clinical trials for nearly two years and this particular viral vector has been slow to start up again. Likewise, MLV retroviruses were used to introduce the genes to correct severe-combined immunodeficiency disease (SCID) or the "French bubble-boy" disease and the trial was stopped because some of the patients developed leukemia. Lentiviruses are generally regarded to be safer than oncoretroviral-based (MLV) vectors that were used to treat X-linked SCID because they are thought not to stimulate ontogenesis. The following is a review article (http://www.virxsys.com/doc/peer/mani...regulatory.pdf) on the subject, if anybody wants to read about use of lentiviral vectors in clinical trial.

Thus, in my opinion, Innurex is still a ways from clinical trial. It is important for the work on rat spinal cord injury to be published and replicated by other laboratories. Gene therapy involving viruses have not had an easy time going into clinical trial and it is not clear that all the regulatory hurdles will be cleared in the near future. On the other hand, I am very excited about this study because it strongly suggests that retinoic acid may be a potential treatment for spinal cord injury. Please note that there are other ways to stimulate retinoic acid receptor expression in cells. For example, as pointed out by the paper cited below, estrogen upregulates RAR-alpha-1 receptors in cells. So, there may be alternative approaches to achieving the same goal, as opposed to using a lentivirus mediated gene therapy.

Wise.

References

Zechel C (2005). Requirement of retinoic acid receptor isotypes alpha, beta, and gamma during the initial steps of neural differentiation of PCC7 cells. Mol Endocrinol 19: 1629-45. Retinoic acid (RA) is indispensable for morphogenesis and differentiation of several tissues, including the nervous system. The requirement of the RA receptor (RAR) isotypes alpha, beta, and gamma and the putative role of retinoid X receptor-(RXR) signaling in RA-induced neural differentiation, was analyzed. For this compound-selective retinoids and the murine embryonal carcinoma cell line PCC7, a model system for RA-dependent neural differentiation was used. The present paper shows that proliferating PCC7 cells primarily express RXRalpha and RARalpha, lower levels of RXRbeta, and barely detectable amounts of RARbeta, RARgamma, and RXRgamma. At receptor-selective concentrations, only a RARalpha or RARgamma agonist induced the typical tissue-like differentiation pattern consisting of neuronal and nonneuronal cells. Differentiation-associated processes, such as the down-regulation of Oct4, up-regulation of certain nuclear receptors and proneuronal genes, and the induction of neuronal markers could be triggered by receptor-selective concentrations of a RARalpha-, beta-, or gamma-selective agonist, although with distinct efficacy. The differences are only partially explained by the distinct RARalpha, beta, and gamma expression levels and the dissociation constants for the bound retinoids, suggesting differential requirement of RAR isotypes during the initial stages of neural differentiation of PCC7 cells. Institute of Physiological Chemistry and Pathobiochemistry, Johannes Gutenberg-University, Medical School, Duesberg Weg 6, 55099 Mainz, Germany. zechel@uni-mainz.de
Link Here

Chen SJ, Chen LJ and Zhou GB (2005). [Basic and clinical studies of the gene product-targeting therapy based on leukemogenesis--editorial]. Zhongguo Shi Yan Xue Ye Xue Za Zhi 13: 1-8. In the last twenty years, using all-trans retinoic acid (ATRA) as a differentiation inducer, Shanghai Institute of Hematology has achieved an important breakthrough in the treatment of acute promyelocytic leukemia (APL), which realized the theory of reversing phenotype of cells and provided a successful model of differentiation therapy in cancers. Our group first discovered in the world the variant chromosome translocation t(11;17)(q23;q21) of APL, and cloned the PML-RAR alpha, PLZF-RAR alpha and NPM-RAR alpha fusion genes corresponding to the characterized chromosome translocations t(15;17); t(11;17) and t(5;17) in APL. Moreover, establishment of transgenic mice model of APL proved their effects on leukemogenesis. The ability of ATRA to modify the recruitment of nuclear receptor co-repressor with PML-RAR alpha but not PLZF-RAR alpha caused by the variant chromosome translocation elucidated the therapeutic mechanism of ATRA from the molecular level and provides new insight into transcription-modulating therapy. Since 1994, our group has successfully applied arsenic trioxide (As(2)O(3)) in treating relapsed APL patients, with the complete remission rate of 70% - 80%. The molecular mechanism study revealed that As(2)O(3) exerts a dose-dependent dual effect on APL. Low-dose As(2)O(3) induced partial differentiation of APL cells, while the higher dose induced apoptosis. As(2)O(3) binds ubiquitin like SUMO-1 through the lysine 160 of PML, resulting in the degradation of PML-RAR alpha. Taken together, ATRA and As(2)O(3) target the transcription factor PML-RAR alpha, the former by retinoic acid receptor and the latter by PML sumolization, both induce PML-RAR alpha degradation and APL cells differentiation and apoptosis. Because of the different acting pathways, ATRA and As(2)O(3) have no cross-resistance and can be used as combination therapy. Clinical trial in newly diagnosed APL patients showed that ATRA/As(2)O(3) in combination yields a longer disease-free survival time. With the median survival of 18 months, none of the 20 cases in combination treatment relapsed, whereas 7 relapsed in 37 cases in mono-treatment. This is the best clinical effect achieved in treating adult acute leukemia to this day, possibly making APL the first adult curable leukemia. Based on the great success of the pathogenetic gene target therapy in APL, this strategy may extend to other leukemias. Combination of Gleevec and arsenic agents in treating chronic myeloid leukemia has already make a figure both in clinical and laboratory research, aiming at counteracting the abnormal tyrosine kinase activity of ABL and the degradating BCR-ABL fusion protein. In acute myeloid leukemia M(2b), using new target therapy degradating AML1-ETO fusion protein and reducing the abnormal tyrosine kinase activity of c-kit will also lead to new therapeutic management in acute leukemias. Link Here

[gmebius]

Hola Fernando,

Soy de San Luis Potosi.
De donde eres tu?

saludos

[Fernando]

Que tal Gunnar

Yo vivo en Ensenada y aqui esta mi correo electronico fjaimes@bajamexinternacional.com

Y de donde eres porque tu nombre no es muy Mexicano que digamos.

Saludos
Fernando