Brain boost
By Patrick BarryWeb edition : Friday, August 15th, 2008 Text Size Protein improves old rats’ ability to form new memories You can teach an old rat new tricks, if you give him a shot of this stuff.

A form of gene therapy that boosted a protein in aged rats’ brains significantly improved the rats’ performance on memory tests, according to a new study.

The protein — called glial cell line-derived neurotrophic factor, or GDNF — holds promise as a way to relieve memory and motion control loss that comes with old age and with diseases such as Parkinson’s and Alzheimer’s, the researchers report in the September Neurobiology of Aging.

Previous GDNF trials on people with Parkinson’s disease suggested that direct injection of the protein into patients’ brains may have improved verbal memory and motion control. But the new study offers a clearer demonstration that the protein can partially restore age-related memory loss.

“This is a confirmation that this is a really useful molecule,” comments Steven Gill, a consultant neurosurgeon at Frenchay Hospital in Bristol, England, who helped run the earlier human GDNF trial. “If we can master those — the neurotrophins, the delivery — then we can tackle these major neurodegenerative diseases.”


GDNF is normally produced in the brain by support cells that surround and nourish nerve cells. The protein stimulates nerve cells, causing them to thrive and to sprout new connections with neighboring neurons. These connections allow neurons to communicate and are believed to be crucial for how the brain stores new memories.


As rats and people reach old age, natural production of this protein appears to taper off, some research suggests. To give elderly but otherwise healthy rats’ brains a boost, a team led by Coral Sanfeliu of the Institute of Biomedical Research of Barcelona, in Spain, loaded a harmless virus with the gene that encodes GDNF. The researchers designed the virus to enter a specific kind of support cell in the brain, called an astrocyte, and insert the gene into the cell’s DNA. Then they injected the engineered virus directly into a memory-forming region of the brain called the hippocampus.


Two weeks after injection, the aged rats’ performance on a standard memory test improved by about 40 percent. That improvement closed half the performance gap between untreated elderly rats and young rats.

Placed in a small pool of water, the rats had to remember the location of a platform hidden just beneath the surface.

“As a proof of principle, it’s a great find,” comments Nik Patel, a consultant neurosurgeon and colleague of Gill’s at Frenchay Hospital.

Using a virus to insert a gene into a person’s DNA is still a risky procedure, Patel cautions. “At the moment I certainly wouldn’t rely on it as fully safe, because there’s always the possibility of [tumors] over the long term.” That’s because inserting a gene can sometimes create cancer-causing mutations in the patient’s DNA.

Scientists are divided over whether viruses or direct injection through conventional catheters will be the more practical way to get GDNF into patients’ brains. But they agree that the protein could eventually provide a new way to treat age- and disease-related mental decline.

“Could this be the Botox of the brain?” Patel asks. “Who knows?”

a virus is smaller than the GDNF protein serum, so it will cross the BBB
for sure... no pumps needed, - according to my reliable source...

and the botox serum is not a near so great as this...

I had to jump in here. The viruses used in these experiments are huge, compared to the size of the GDNF protein molecule itself, many thousands of times larger.
.
Molecular size in proteins and nucleoprotein virus is expressed in kD, or kiloDaltons. A Dalton is equivalent to the mass of one hydrogen atom, or one atomic mass unit. A kilodalton is 1000 times that mass.
The molecular mass of GDNF is 21 kD, whereas these viruses have masses of millions of kD. Each virus is made up of thousands of protein molecules, most of which are much larger than the GDNF molecule.

These viruses, which are chosen because they have a tendency to enter certain kinds of cells, are modified in the laboratory to contain the DNA information which, when taken in by certain brain cells, provide the information code which allows them to make GDNF. The GDNF protein made inside the cells can then be released to enhance the survival and function (-troph) of surrounding nerve (neuro) cells.

Robert

for the info.-pretty sure I would never have learned that on my own!

GDNF
Native glial cell line-derived neurotrophic factor (GDNF) is a 40 kDa glycosylated, disulfide-linked homodimer that is a member of the TGF-beta superfamily. Mature rat and human GDNF exhibit 93% amino acid sequence identity and show considerable species cross-reactivity. Cells known to express GDNF include Sertoli cells, type 1 astrocytes, Schwann cells, neurons, and skeletal muscle cells.

http://www.rndsystems.com/molecule_d...FQFqxwodUERSjA

Good reference, Tena. The glycosylated, disulfide-bonded homodimer has a molecular weight of 40 kDa. The monomer thus has one-half the weight of the dimer.

Robert

to Bristol ?

Is this some other GDNF ?

If it is the "original", what are the constraints on its use, anyone know ?

Neil.

The GDNF that Amgen used is 'synthetic' gdnf and it had already gone through extensive testing on animals, so it could be used in human trials now - if only Amgen would release it.

Natural GDNF will have to go through all of the tests on animals for safety before they can use it in human trials.

So the way I look at, it is TIME - Natural GDNF must go through more testing for safety -- which will take more time before it can be used in human trials. Amgen's synthetic GDNF has no such constraints.

thanks,