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Topical Treatment with ALT-111 and Possibly Aminoguanidine


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#1 sapentia

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Posted 26 October 2010 - 03:25 PM


With regard to skin aging as a function of AGE's (advanced glycation end products) I am conceptually exploring the possibility of topical treatment with ALT-111 (Alagebrium) and/or Aminoguanidine. The logic is fairly simple: ALT-111 in a lotion carrier would serve to break existing AGE bonds while Aminoguanidine would theoretically serve to inhibit reformation of those bonds once broken. To my knowledge no human studies have been conducted along these lines, however, there was a study with rat skin which showed very good results with ALT-111 treatment. I also found another study with standalone Aminoguanidine treatment on human skin samples with positive results. The ALT-111 treatment was for 3 days, with results being measured 3 days, 12 days, and 36 days following treatment. Skin elasticity was improved 21% at day 3 following treatment and was still at 16% increased elasticity at day 36. Again, this was following only 3 days of initial treatment.

Reference for ALT-111 study: (please see attached graph a and graph b)
Arch Biochem Biophys. 2003 Nov 1;419(1):89-96.
Therapeutic potential of breakers of advanced glycation end product-protein crosslinks.
Vasan S, Foiles P, Founds H.
Alteon Inc., 170 Williams Drive, Ramsey, NJ 07446, USA.
svasan@alteon.com
PMID: 14568012

Reference for Aminoguanidine study: (please see attached PDF)

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#2 infinityXme

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Posted 26 October 2010 - 08:26 PM

With regard to skin aging as a function of AGE's (advanced glycation end products) I am conceptually exploring the possibility of topical treatment with ALT-111 (Alagebrium) and/or Aminoguanidine. The logic is fairly simple: ALT-111 in a lotion carrier would serve to break existing AGE bonds while Aminoguanidine would theoretically serve to inhibit reformation of those bonds once broken. To my knowledge no human studies have been conducted along these lines, however, there was a study with rat skin which showed very good results with ALT-111 treatment. I also found another study with standalone Aminoguanidine treatment on human skin samples with positive results. The ALT-111 treatment was for 3 days, with results being measured 3 days, 12 days, and 36 days following treatment. Skin elasticity was improved 21% at day 3 following treatment and was still at 16% increased elasticity at day 36. Again, this was following only 3 days of initial treatment.

Reference for ALT-111 study: (please see attached graph a and graph b)
Arch Biochem Biophys. 2003 Nov 1;419(1):89-96.
Therapeutic potential of breakers of advanced glycation end product-protein crosslinks.
Vasan S, Foiles P, Founds H.
Alteon Inc., 170 Williams Drive, Ramsey, NJ 07446, USA.
svasan@alteon.com
PMID: 14568012

Reference for Aminoguanidine study: (please see attached PDF)



Interesting. Keep us updated.

#3 maxwatt

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Posted 26 October 2010 - 11:03 PM

The problem I see with this is that ALT-711 does not break pentosidine glycation products. which comprises the majority of skin AGES that make it inflexible and wrinked. :(

I know of a stilbene molecule that prevents pentosidine glycation, work is being done with it, nd hopefully it will lead to something that also breaks pentosidineglycation bonds. However it is not available at this point unless you have a chem lab or a botanical extraction facility.

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#4 sapentia

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Posted 27 October 2010 - 02:52 AM

The problem I see with this is that ALT-711 does not break pentosidine glycation products. which comprises the majority of skin AGES that make it inflexible and wrinked. :(

I know of a stilbene molecule that prevents pentosidine glycation, work is being done with it, nd hopefully it will lead to something that also breaks pentosidineglycation bonds. However it is not available at this point unless you have a chem lab or a botanical extraction facility.



If this is the case, what would you say is responsible for the rapid improvement seen in the above cited study with ALT-711?

#5 maxwatt

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Posted 27 October 2010 - 04:26 AM


The problem I see with this is that ALT-711 does not break pentosidine glycation products. which comprises the majority of skin AGES that make it inflexible and wrinked. :(

I know of a stilbene molecule that prevents pentosidine glycation, work is being done with it, nd hopefully it will lead to something that also breaks pentosidineglycation bonds. However it is not available at this point unless you have a chem lab or a botanical extraction facility.



If this is the case, what would you say is responsible for the rapid improvement seen in the above cited study with ALT-711?


The improvements cited in the abstract were "Oral administration of ALT-711 has resulted in a rapid improvement in the elasticity of stiffened myocardium in experimental animals. Topical administration of ALT-711 was effective in improving the skin hydration of aged rats. "

The myocardium is not the skin, different kinds of cross linked AGEs. Skin hydration will improve appearance, but not restore elasticity or mask larger wrinkles.

#6 sapentia

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Posted 27 October 2010 - 01:37 PM

[/quote]

The improvements cited in the abstract were "Oral administration of ALT-711 has resulted in a rapid improvement in the elasticity of stiffened myocardium in experimental animals. Topical administration of ALT-711 was effective in improving the skin hydration of aged rats. "

The myocardium is not the skin, different kinds of cross linked AGEs. Skin hydration will improve appearance, but not restore elasticity or mask larger wrinkles.
[/quote]


I agree, but that is not the part of the study I was referring too.

From the cited study:

Potential dermatological application of ALT-711
One of the consequences of aging is the progressive
reduction in the thickness of the dermis causing dehydration
of skin and loss of elasticity. Non-enzymatic
crosslinking of skin collagen via AGEs is considered to
contribute to age-related skin stiffening [94,95]. The effect
of topical application of ALT-711 on skin elasticity
and hydration of aged Fisher 344 male rats was studied.
ALT-711 was mixed at 5% concentration with a moisturizing
lotion and applied to the skin of 24-month-old
rats for 3 days. The treatment was stopped and skin
elasticity and hydration were measured at 3, 12, and 36
days. Results (Figs. 5 and 6) indicated that ALT-711-treatment
improved the water content and elasticity of the aged rat
skin, compared to the control rats treated
only with the lotion. Whether this action by ALT-711 in
animals can be extended to human remains to be
studied.

Fig. 5. Topical ALT-711 application increases skin elasticity of aged
rats. Twenty-four-month-old Fischer 344 rats were used to determine
the effect of topical application of ALT-711 on skin elasticity. A 5%
solution of ALT-711 (w/w) in a generic skin creme or the creme alone
was applied for 3 days on a shaved area on the backside of the animals.
Skin strips were analyzed for tensile strength using an Instron automated
materials testing system. Elasticity was determined by calculating
Youngs modulus from the linear portion of the stress-strain
curve. Two groups of animals were similarly treated for 3 days and
then left untreated. The elasticity measurements on these animals were
repeated on the 9th and 33rd days after stopping the treatment.

Figure 5 shows an initial increase of roughly 20% elasticity 3 days following treatment with the elasticity remaining 16% above the untreated control 33 days later. I wasn't as interested in the skin hydration component since increasing skin hydration isn't as difficult as increasing elasticity in my opinion.

Is it possible that other less prominent forms of AGE's present in the skin are broken down by the ALT-711 even though the pentosidine glycation products are not?

#7 maxwatt

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Posted 27 October 2010 - 02:49 PM

Yes.

#8 sapentia

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Posted 02 November 2010 - 03:54 PM

I began topical treatment with ALT-711 (alagebrium chloride) and aminoguanidine yesterday. I started by preparing a smaller sample batch which should last around 5 days +/-. I used Dermalastyl as the base to which I added ALT-711 to 5.0% concentration and aminoguanidine to 1.0% concentration. Concentrations are based on mass and were measured by a milligram scale. The final emulsion mixed well but ended up being a much thinner consistency than the base product had. I found this helpful as it allowed less product application to achieve coverage.

Results will be subjective. I am applying the mixture to my right hand while not applying it to my left in an attempt to establish a control. I am applying it to my face as well but decided against using a control with one side remaining untreated.

My protocol will be once a day morning application. Evenings will remain existing my tretinoin protocol. Nutrition has been and will remain solid with a healthy balance of all essentials as well as Biosil, astaxanthin/lutein/zeaxanthin, MSM, EPA/DHA/DPA, and centrophenoxine to name a few.

I will update when I can make a meaningful assessment.

#9 VictorBjoerk

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Posted 06 November 2010 - 12:53 AM

I began topical treatment with ALT-711 (alagebrium chloride) and aminoguanidine yesterday. I started by preparing a smaller sample batch which should last around 5 days +/-. I used Dermalastyl as the base to which I added ALT-711 to 5.0% concentration and aminoguanidine to 1.0% concentration. Concentrations are based on mass and were measured by a milligram scale. The final emulsion mixed well but ended up being a much thinner consistency than the base product had. I found this helpful as it allowed less product application to achieve coverage.

Results will be subjective. I am applying the mixture to my right hand while not applying it to my left in an attempt to establish a control. I am applying it to my face as well but decided against using a control with one side remaining untreated.

My protocol will be once a day morning application. Evenings will remain existing my tretinoin protocol. Nutrition has been and will remain solid with a healthy balance of all essentials as well as Biosil, astaxanthin/lutein/zeaxanthin, MSM, EPA/DHA/DPA, and centrophenoxine to name a few.

I will update when I can make a meaningful assessment.


Interesting, looking forward to see some before and after pictures appearing here. :)

#10 niner

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Posted 06 November 2010 - 02:14 AM

I began topical treatment with ALT-711 (alagebrium chloride) and aminoguanidine yesterday. I started by preparing a smaller sample batch which should last around 5 days +/-. I used Dermalastyl as the base to which I added ALT-711 to 5.0% concentration and aminoguanidine to 1.0% concentration. Concentrations are based on mass and were measured by a milligram scale. The final emulsion mixed well but ended up being a much thinner consistency than the base product had. I found this helpful as it allowed less product application to achieve coverage.

Results will be subjective. I am applying the mixture to my right hand while not applying it to my left in an attempt to establish a control. I am applying it to my face as well but decided against using a control with one side remaining untreated.

My protocol will be once a day morning application. Evenings will remain existing my tretinoin protocol. Nutrition has been and will remain solid with a healthy balance of all essentials as well as Biosil, astaxanthin/lutein/zeaxanthin, MSM, EPA/DHA/DPA, and centrophenoxine to name a few.

I will update when I can make a meaningful assessment.

Sapentia, this is a brilliant skin experiment. I'm sure that a lot of people will be interested in your results. I'd like to put in a plug for a split-face control. I've run a couple of these, and it is a very good way to sort out effects. I'm glad you're doing split hands, but hope you will reconsider with the face. Where did you manage to find ALT-711?

#11 curious_sle

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Posted 21 November 2010 - 07:13 PM

Sapentia, this is a brilliant skin experiment. I'm sure that a lot of people will be interested in your results. I'd like to put in a plug for a split-face control. I've run a couple of these, and it is a very good way to sort out effects. I'm glad you're doing split hands, but hope you will reconsider with the face. Where did you manage to find ALT-711?


try stenlabs.com

#12 niner

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Posted 22 November 2010 - 01:16 AM


Where did you manage to find ALT-711?

try stenlabs.com

OK, I checked it out, and it's disturbing. They have something that they call "ALT-711 (thiazolium chloride)". The problem is, first of all, ALT-711 isn't thiazolium chloride. It is an oxo-phenethyl dimethyl thiazolium chloride, which is a completely different molecule. If that were the only problem, I might give them the benefit of the doubt and say that they "abbreviated" the name. (Real chemists don't do this.) HOWEVER, they show a structure, which should remove all ambiguity. The structure they show is not even a thiazole, much less the correct one!

Sorry, this is a massive fail. I wouldn't do business with these clowns. How in the world would you know what you were getting?

#13 rooter

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Posted 03 December 2010 - 06:09 PM

Yikes. So where to get alagebrium?

#14 sapentia

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Posted 13 December 2010 - 04:45 PM

Update:

After roughly 6 weeks of treatment with ALT-111 at a 5% concentration in a standard moisturizing carrier I cannot discern any difference in visible skin quality. In addition to full face application I did a split hand treatment. Again, I can discern no appreciable difference between my two hands. It is possible that there may be some level of differentiation which isn't apparent through visual assessment. My skin regimen is fairly thorough in both nutrition and supplementation as well as external product application which may not have left a significant amount of room for improvement in areas such as hydration and elasticity. I will not be continuing the external application of ALT-111.

As Maxwatt posted earlier a compound which breaks pentosidineglycation bonds would likely be much more effective though that is yet to be seen. Supposedly, trans 3,5,7,4'-tetrahydro-stilbene breaks these bonds, but it is not available in pure form. I believe it is a component of the herb Fo-Ti which is available as a 12:1 extract potency. Whether this product externally applied would contain a strong enough stilbene concentration to have any effect is uncertain. Topically, unprocessed Fo-Ti is used to treat skin conditions such as acne, athlete's foot, dermatitis, razor burn, and scrapes.

#15 curious_sle

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Posted 29 December 2010 - 10:13 AM

um, anyone familiar with htis? http://www.freepaten...09/0047224.html

"
Various products capable of inhibiting this glycation reaction are known, including aminoguanidine, which is the inhibitor that is the most widely known (U.S. Pat. No. 5,130,324), taurine (Devamanoharan P. S., 1997, Molecular and Cellular Biochemistry, 177, 245-250), carnosine (Hipkiss A. R., 1995, Febs Letters, 371, 81-85), certain vitamins (B1, B6), bilberry extracts (FR-2 802 425), hydroxystilbenes such as resveratrol (FR-2 796 278) and 3,3′,5,5′-tetrahydroxystilbene (FR-2 802 420) and ergothioneine (FR-2 810 548).

In addition to compounds that inhibit the glycation of proteins, it is known that certain compounds (including the product ALT711 manufactured by Alteon Corporation) are capable of breaking the crosslinking bonds between two proteins, formed as a result of the Maillard reaction (Melton L., Age breakers—Rupturing the body's sugar - protein bond might turn back the clock, Sci. Am., 2000, 283(1): 16; Asif M. et al., An advanced glycation end - product crosslink breaker reverses age - related increases in myocardial stiffness, Proc. Natl. Acad. Sci., 2000, 97(6), 2808-2813).

However, to the Applicant's knowledge, it has never yet been suggested that compounds capable of breaking the crosslinking bonds between two proteins might be useful as anti-glycation agents for topical application to the skin, for the purpose especially of treating the signs of ageing of the skin. It has not been suggested either that N-hydroxy imides were useful for this purpose.

The Applicant has now discovered, surprisingly and unexpectedly, that certain N-hydroxy imides have the property of reducing or even inhibiting the glycation of proteins and thus of acting firstly on the age-related loss of tonicity of the skin, and secondly on the “orange-peel” appearance.

It has moreover been demonstrated that these N-hydroxy imides also have antioxidant properties that allow them to act on the causes of photo-ageing, in addition to their effect on the previously described signs of chronological ageing. They therefore constitute compounds of choice for efficiently combating all the effects of age on the skin, whether of chronological or actinic origin.
"

Edited by curious_sle, 29 December 2010 - 10:16 AM.


#16 poolboy

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Posted 07 March 2012 - 05:12 PM

Renoprotective antioxidant effect of alagebrium in experimental diabetes

http://ndt.oxfordjou...1/3474.abstract

"ALA [alagebrium] significantly reduced not only urinary albumin excretion and renal pathological changes but also accumulation of pentosidine and nitrotyrosine and expression of NADPH oxidase subunits in db/db mice regardless of treatment protocol.

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#17 poolboy

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Posted 07 March 2012 - 05:26 PM

For those interested, Alagebrium appears to be blunting Methylglyoxal. It's not just for alpha-diketones any more.


Methylglyoxal-induced mitochondrial dysfunction in vascular smooth muscle cells
http://www.sciencedi...006295209001518



" The levels of mitochondrial reactive oxygen species (mtROS) and ONOO were significantly increased by MG treatment. Application of ONOO specific scavenger uric acid lowered the level of mtROS. MG significantly enhanced the production of mitochondrial superoxide (O2http://cdn.els-cdn.com/sd/entities/rad) and nitric oxide (NO), which were inhibited by SOD mimic 4-hydroxy-tempo and mitochondrial nitric oxide synthase (mtNOS) specific inhibitor 7-nitroindazole, respectively. The activity of MnSOD was decreased by MG treatment. Furthermore, MG decreased respiratory complex III activity and ATP synthesis in mitochondria, indicating an impaired mitochondrial respiratory chain. AGEs cross-link breaker alagebrium reversed all aforementioned mitochondrial effects of MG.


Alagebrium attenuates acute methylglyoxal-induced glucose intolerance in Sprague-Dawley rats
http://www.ncbi.nlm....les/PMC2823362/
Alagebrium acutely attenuated MG-induced glucose intolerance, suggesting a possible preventive role for alagebrium against the harmful effects of MG.




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