[lurkingforacure]

if you go to amt's website (amt is the licensee of amgen's gdnf), there is a fascinating video about viral vectors...very encouraging. AMT is a relatively young company (1998) but this is quite impressive, and hopeful. Of course, they have the benefit of knowing already that gdnf works, the only trick is how to get it to where it's needed...I think this is the link to the video:

http://www.amtbiopharma.com/mod.php?...age&page_id=74

[paula_w]

patent filed by Amgen in Jan. 2004 and published Sept. 9, 2004. This was for Amgen's GDNF gene.
Glial derived neurotrophic factor


Abstract A novel neurotrophic factor referred to as glial derived neurotrophic factor (GDNF) has been identified and isolated from serum free growth conditioned medium of B49 glioblastoma cells. Rat and human genes encoding GDNF have been cloned and sequenced. A gene encoding GDNF has been subcloned into a vector, and the vector has been used to transform a host cell in order to produce biologically active GDNF in a recombinant DNA process.
Inventors: Lin, Leu-Fen H.; (Boulder, CO) ; Collins, Franklin D.; (Agoura Hills, CA) ; Doherty, Daniel H.; (Boulder, CO) ; Lile, Jack; (Nederland, CO) ; Bektesh, Susan; (Boulder, CO) Correspondence Name and Address: AMGEN INCORPORATED
MAIL STOP 27-4-A
ONE AMGEN CENTER DRIVE
THOUSAND OAKS
CA
91320-1799
US
Assignee Name and Adress: Amgen Inc.


Assignee Name and Adress: Amgen Inc.

Serial No.: 758622 Series Code: 10 Filed: January 14, 2004
http://appft1.uspto.gov/netacgi/nph-...gdnf+AND+amgen



"FIELD OF THE INVENTION

[0001] The present invention relates to neurotrophic factors and glial derived neurotrophic factor (GDNF) in particular. Also included within this invention are processes for purification of GDNF from natural sources and processes for cloning rat and human genes encoding GDNF, as well as the nucleic acid sequence of the rat and human genes that encode GDNF. The GDNF gene has been subcloned into an expression vector, and the vector used to express biologically active GDNF. In addition, this invention includes the use of GDNF for preventing and treating nerve damage and nerve related diseases such as Parkinson's disease.

[0002] Antibodies to GDNF are disclosed, as well as methods for identifying members of the GDNF family of neurotrophic factors. And finally, methods are described for preventing or treating nerve damage by implanting into patients cells that secrete GDNF. "

[caldeerster]

If the AMT delivery system for GDNF involves stereotactic injections, or is it a small molecule system, where the cell is programmed to cross the blood brain barrier?

I watched the video and I'm still unclear as to their delivery mechanism.

[paula_w]

oops big goof - below is not the gene therapy study that the thread is about. This is armagen, not AMT, sorry for the big mistake....AMT is a different company and study.

Having said that - this one sounds real good!!

Project Description:

In this project, the GDNF will be delivered to the target region via transport across the BBB, following a non-invasive intravenous administration. To enable transport across the BBB, the GDNF is re-engineered with the molecular Trojan horse technology. The GDNF is fused to a genetically engineered monoclonal antibody, which crosses the BBB via endogenous transport systems. The antibody acts as a molecular Trojan horse, and ferries the attached GDNF across the BBB, from blood, to the target site in brain. The GDNF-antibody combination is a combination molecule, also called a fusion protein. Following manufacture of the new drug, the efficacy of intravenous GDNF-fusion protein in a primate model of PD will be evaluated. In parallel, the potential toxicity of intravenous GDNF-fusion protein will be tested in primates.

read abstract:
http://www.michaeljfox.org/research_...s_3.cfm?ID=440

Originally Posted by caldeerster

If the AMT delivery system for GDNF involves stereotactic injections, or is it a small molecule system, where the cell is programmed to cross the blood brain barrier?

I watched the video and I'm still unclear as to their delivery mechanism.

[lurkingforacure]

Thanks! And by "in parallel", does that mean at the same time? That would speed things up further, for sure.

[paula_w]

One definition of parallel defined as the 'computer' definition, speaks of two operations at the same time and distinguishes it from serial. I thought I copied it but didn't. I'd venture to say yes.

Arma gen - Amgen
"Non-program-specific Funding", 2008, MJFF
I suspect Andy Grove is involved here - but have no reason to say so - lol, so don't quote me.
UCLA

paula

Originally Posted by lurkingforacure

Thanks! And by "in parallel", does that mean at the same time? That would speed things up further, for sure.

[paula_w]

What a mess. I found the armagen study in the list of all funding for neurotrophic factors here at the bottom of page:

http://www.michaeljfox.org/research_...37&search.y=10

Then by clicking on that bottom abstract I found the armagen study:

http://www.michaeljfox.org/research_...s_3.cfm?ID=440

The AMT study, which caldersteer was inquiring about is here and also linked on the home page:

http://www.michaeljfox.org/newsEvent...cle.cfm?ID=401

geez I should just go copy this onto the clognition thread.
paula

[bryn]

There is also some good background on MJFF on trophic factors in the third link (not been here long enough to post a URL!) Explained a few things for me!

Bryn

[caldeerster]

Thanks for clearing that up Paula!

So, basically, that video I watched at the link has nothing to do with this Amgen/Amsterdam licensing agreement. And the Amsterdam delivery mechanism is a trojan horse system, whereby the GDNF will be delivered and ferried to the appropriate part of the brain via a non invasive intravenous mechanism.

Do I have that right?

If so, yes, it sounds remarkably promising.

Caldeerster

[aftermathman]

the method of delivery of the AAV virus however it has / is being used in various forms by Neurologix, Ceregene and Oxford Biomedica in existing gene therapy studies.

I believe in these other studies it is delivered via stereotactic injection in the brain, a procedure not without its risks as Carolyn can evidence. Still a small price to pay if the results are good.

No reason to assume the AMT study will not work in the same way.

AAV was reviewed last year by the FDA when a gene therapy trialist died (not a PD trial) however it was found to be safe and not connected to the death.

Neil.