Nerve Growth Factor and Longevity Options

[Reven]

Interesting article...

http://www.independent.co.uk/news/science/...fe-1674005.html


Most centenarians attribute their great age to some magic elixir or other. The longevity of the Italian scientist Rita Levi-Montalcini, who this week became the first Nobel Prize-winner to reach the age of 100, might be the result of a potion that is a little out of the ordinary: Professor Levi-Montalcini, it is said, puts her undiminished mental vigour down to regular doses of nerve growth factor (NGF) – the discovery that made her famous.

She was awarded the 1986 Nobel Prize for Medicine jointly with an American, Stanley Cohen, for her research into NGF: the proteins and amino-acids which enable the cells of the nervous system to grow and take on specialised tasks. Despite her age, Dr Levi-Montalcini, a neurologist and development biologist, still works every day at the European Brain Research Institute, which she founded in Rome.

During numerous celebrations this week, she claimed that her brain was more vigorous today than it was four decades ago. "If I'm not mistaken," she said, "I can say my mental capacity is greater than when I was 20 because it has been enriched by so many experiences, in the same way that my curiosity and desire to be close to those who suffer has not diminished."

According to Pietro Calissano, who collaborated with the professor on an article for Scientific American in which she announced her discovery in 1979, NGF may have played a direct role in her amazing vitality. "Every day, she takes NGF in the form of eye drops," he said, "but I can't say for sure if this is her secret. At the start, it seemed this molecule's effect was restricted to acting on the peripheral nervous system, but then it emerged that it has a very important role in the brain. Contrary to what was believed, the brain does not have a rigid structure but is in continuous movement, and NGF helps neurons – which we begin to lose between 10 and 15 years old – survive."

Italy pulled out all the stops to honour Dr Levi-Montalcini, with parties, seminars and more awards to add to her pile. Most appreciated of all was a decision by the universities ministry to award her research institute a grant of €500,000 (£448,000). She said: "The scientific director of the institute and I have spent many days wondering how to solve our financial problems." The money gives the institute a few more months' lease of life."

Dr Levi-Montalcini also praised her homeland, adding: "I say to the young, be happy that you were born in Italy because of the beauty of the human capital, both masculine and feminine, of this country ... No other country has such human capital."

Yet the country she loves did all in its power to curtail her career before it began. She was born to a cultured Jewish family in Turin in 1909, the daughter of an electrical engineer and a painter. Defying her father's wishes, she went to medical school and graduated in 1936. She immediately enrolled as a postgraduate, but in the same year Mussolini published his Manifesto for the Defence of the Race, followed in 1938 by new laws banning "inferior races" from education and forcing her out of university.

"Don't fear difficult moments," she said, "the best comes from them." But her "difficult moments" were to last nearly 10 years. She fled to Belgium to continue her studies, but the imminent invasion of the Nazis in 1940 forced her to return to Turin, where she constructed a laboratory in her bedroom. When the Allies bombed the city in 1941, she fled to the countryside and built another lab in a country cottage. Then the German invasion of Italy in 1943 sent her fleeing to Florence, where she lived incognito until the war's end, working as a nurse and doctor among the disease-ridden refugees. After the war she accepted an invitation to study in America, where in the subsequent decades her most important work was done. She only returned to Italy full time after she retired in 1977.

Dr Levi-Montalcini was made a senator for life in 2001 and from 2005 to 2007 she played a vital role in supporting the centre-left government of Romano Prodi, which had a wafer-thin Senate majority and needed every vote to stay afloat. Despite her age, Dr Levi-Montalcini never failed it, earning the wrath of the right-wing opposition in the process.

[prophets]

http://www.sciencedirect.com/science?_ob=A...3ac2c0f44b75808

Abstract

It has been shown that conjunctivally applied NGF in rats can reach the retina and optic nerve. Whether topical eye NGF application reaches the central nervous system is not known. In the present study, we have addressed this question. It was found that topical eye NGF application affects brain cells. Time-course studies revealed that repeated NGF application leads to high concentration of this neurotrophins after 6 h and normal levels after 24 h. Our results also showed that topical eye application of NGF causes an enhanced expression of NGF receptors and ChAT immunoreactivity in forebrain cholinergic neurons, suggesting that ocular NGF application could have a functional role on damaged brain cells. The present findings suggest that eye NGF application can represent an alternative route to prevent degeneration of NGF-receptive neurons involved in disorders such as Alzheimer and Parkinson.



http://www3.interscience.wiley.com/journal...=1&SRETRY=0

Eye drop NGF administration promotes the recovery of chemically injured cholinergic neurons of adult mouse forebrain

We have recently shown that conjunctivally applied nerve growth factor (NGF) in rats can reach the retina, the optic nerve and the CNS. In the present study, we investigated whether NGF application as collyrium can promote the recovery of chemically injured basal forebrain cholinergic neurons. NGF was administered on the eye of adult male mice previously treated i.c.v. with ibotenic acid to impair cholinergic pathways. Mice were tested in the passive avoidance test, and after 2 weeks of NGF administration were killed and the brains used for structural, biochemical and molecular analyses. The results showed that application of NGF on the eye surface protected choline acetyl transferase levels. These findings strengthen the hypothesis that application of NGF on the eye can represent an alternative delivery route to promote the recovery of brain cells during degeneration, including neurons involved in learning and memory activities.


it sounds appealing on the surface, but wouldn't there be a material cancer risk like with any hormone/growth factor?

This post has been edited by prophets: Apr 25 2009, 01:39 PM

[guaif1]

http://www.sciencedirect.com/science?_ob=A...3ac2c0f44b75808

Abstract

It has been shown that conjunctivally applied NGF in rats can reach the retina and optic nerve. Whether topical eye NGF application reaches the central nervous system is not known. In the present study, we have addressed this question. It was found that topical eye NGF application affects brain cells. Time-course studies revealed that repeated NGF application leads to high concentration of this neurotrophins after 6 h and normal levels after 24 h. Our results also showed that topical eye application of NGF causes an enhanced expression of NGF receptors and ChAT immunoreactivity in forebrain cholinergic neurons, suggesting that ocular NGF application could have a functional role on damaged brain cells. The present findings suggest that eye NGF application can represent an alternative route to prevent degeneration of NGF-receptive neurons involved in disorders such as Alzheimer and Parkinson.



http://www3.interscience.wiley.com/journal...=1&SRETRY=0

Eye drop NGF administration promotes the recovery of chemically injured cholinergic neurons of adult mouse forebrain

We have recently shown that conjunctivally applied nerve growth factor (NGF) in rats can reach the retina, the optic nerve and the CNS. In the present study, we investigated whether NGF application as collyrium can promote the recovery of chemically injured basal forebrain cholinergic neurons. NGF was administered on the eye of adult male mice previously treated i.c.v. with ibotenic acid to impair cholinergic pathways. Mice were tested in the passive avoidance test, and after 2 weeks of NGF administration were killed and the brains used for structural, biochemical and molecular analyses. The results showed that application of NGF on the eye surface protected choline acetyl transferase levels. These findings strengthen the hypothesis that application of NGF on the eye can represent an alternative delivery route to promote the recovery of brain cells during degeneration, including neurons involved in learning and memory activities.


it sounds appealing on the surface, but wouldn't there be a material cancer risk like with any hormone/growth factor?

does anyone know if there is a product, NGF, that can be purchased?

[mrak1979]

I'd be interested also.... anybody know?

[Bluenoise]

does anyone know if there is a product, NGF, that can be purchased?

Only for research use that I know of. Even if they sold it to you it would be extreemly expensive.

[Bluenoise]

*ahem*
http://www.prospecbio.com/Beta-Nerve_Growt...CFSMeDQodkBWe9Q

Pretty expensive. They take credit card so you don't need a PO to order.

This post has been edited by Bluenoise: Apr 30 2009, 01:41 AM

[youandme]

Sounds fascinating..have they tried it out on any humans yet ...if not why not ?!

[zorba990]

Sounds fascinating..have they tried it out on any humans yet ...if not why not ?!

What about using acetyl l-carnitine arginate ?
http://www.iherb.com/Jarrow-Formulas-ALCA-...sules/2495?at=0

[prophets]

anything that stimulates growth hormone should in turn stimulate NGF/BDNF. I would think alpha-gpc would be ideal.

I would still like to know Dr. Levi-Montalcini's regimen... exactly how many drops, concentration of the NGF (in saline?), when, etc...

[bgwithadd]

Question is, what will you get from a microgram? You might get a lot more out of trying to up in it other ways like lithium, brewer's yeast, choline, PS, lecithin, etc.

[Lufega]

I was just reading about her research and was going to post about it. She lived to 100 without any obvious complications with hormones imbalances, cancer, etc. Does it say anywhere how long she's been using the drops? We need a source of this stuff, fast!

[Doc Eight or DE]

So advantages of using NGF from there source vs cobra venom would be?

[RighteousReason]

http://findarticles.com/p/articles/mi_m0IS...ag=content;col1

[prophets]

I was just reading about her research and was going to post about it. She lived to 100 without any obvious complications with hormones imbalances, cancer, etc. Does it say anywhere how long she's been using the drops? We need a source of this stuff, fast!

I thought about this also, and tried to surf around and find the answer online for a few hours (to no avail). I also didn't see any human studies with in vivo usage of NGF when I looked (to try to find dosage guidelines). You can buy NGF (I looked into it), but you don't know how she's diluting it or what she's doing regimen-wise. I know an Italian researcher who analyzes BCAA/Whey protein for sarcopenia treatment and I thought about trying to have him ask her, but I decided against it.

You'd really have to track down exactly what she's doing and then analyze that against your other options. And her genetic make-up is not yours. You may still be risking a glioma, etc.

[Lufega]

http://findarticles.com/p/articles/mi_m0IS...ag=content;col1

Thanks for this article. I have an old bottle of lion's mane I restarted using. This is a great little supp and I feel a slight improvement in cognitive function. I don't know why I put it down in the first place.

[Anthony]

Thanks for this article. I have an old bottle of lion's mane I restarted using. This is a great little supp and I feel a slight improvement in cognitive function. I don't know why I put it down in the first place.

The article is discussing another drug but mentions NGF. It states that NGF cannot pass through the blood brain barrier. Maybe it is referring to NGF which is ingested orally?

http://www.medicalnewstoday.com/articles/155547.php

This post has been edited by Anthony: Jul 17 2009, 04:19 AM

[prophets]

The article is discussing another drug but mentions NGF. It states that NGF cannot pass through the blood brain barrier. Maybe it is referring to NGF which is ingested orally?

she did it through eye drops.

[Ben K]

Here's a patent application for "Use of nerve growth factor in eye-drops for therapy of pathologies of the central nervous system, such as Alzheimer's and Parkinson's disease":

http://www.freshpatents.com/-dt20090507pta...ype=description

http://www.faqs.org/patents/app/20090118177

"The possibility that NGF could exert a biological action on brain tissues following topical ophthalmic administration was hardly foreseeable, above all, in view of the fact that—as highlighted above—NGF is a molecule of considerable size (26,800 dalton) with a complex structure. In order for a molecule to have any action on brain tissues, then—once instilled on the eye surface—it must be able to pass through the eye tissues and reach the optic nerve and cerebrospinal fluid in order to exert its own biological activity on the brain region. In current practice, ocular administration is not used for treating brain pathologies. The foregoing is due to the fact that all the known studies concerning NGF use in brain pathologies have only employed intracerebral administration. "In actual fact, although having a complex structure and a high molecular weight, NGF has both hydrophilic and hydrophobic structural groups which enable it to pass through the homologous (lipid and hydrophilic) anatomical barriers. Moreover, a fundamental feature of NGF is that once it reaches the target organs even at very low, but biologically active, concentrations, it can stimulate the endogenous production of NGF by the tissue itself. The presence of an endogenous fraction of NGF is clearly borne out by the results of experiments (which will be illustrated below) on the passage of NGF through tissues. These results also show that a concentration gradient is not maintained from the external surface of the eye towards the brain, as had been hypothesised for a simple diffusion mechanism through tissues.

"In order to produce the preparation according to the present invention, suitable procedures for NGF extraction and purification are reported in the aforesaid literature. The technique of Bocchini and Angeletti, briefly reported here, was used for experiments concerning the present invention. Submandibular glands of adult male mice are extracted in sterile conditions and the tissues thereof are homogenised, centrifuged and dialysed. The suspension is then made to pass through successive cellulose columns, whereon the NGF is adsorbed. The NGF is then eluted from the column by means of a 0.4 M sodium chloride buffer. The samples thus obtained are analysed spectrophotometrically at a wavelength of 280 nm to identify the NGF containing fractions. These fractions are dialysed and the NGF is lyophilised in sterile conditions and refrigerated at −20° C.

"A medicinal product according to the present invention and suitable for ocular surface administration preferably contains, either alone or in association with one or more other active ingredients, between 1 and 1000 μg/ml of NGF. If the product is in the form of an aqueous solution (eye-drops), the NGF concentration may preferably be in the range 10-500 μg/ml, and still more preferably in the range 200-250 μg/ml. A specific formulation for eye-drops may contain, for example, 200 μg/ml of NGF in a 0.9% sodium chloride physiological solution, or in a balanced saline solution (BSS®): in both cases, the solution is isotonic with tear fluid and thus well tolerated by the eye. However, it is also possible to use hypotonic solutions."

[prophets]

http://www.prospecbio.com/Beta-Nerve_Growth_Factor/

at $1,000 for 100 ug, if i'm doing the math right, that's like $60,000 for a 200 ug/ml solution. bit pricey. i know there were NGF tests done through intranasal administration; not sure which has better efficacy or price/performance advantage.

[Googlebot]

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