ALT-711: Safe and Effective Anti-AGE-ing Therapy

As we age, a non-enzymatic reaction between sugars in the blood and amino groups in our body’s proteins, fats, and DNA, produces compounds called advanced glycation end-products (appropriately called AGEs). AGEs bond to one another, creating crosslinks between proteins that disrupt normal cellular activity. By stiffening collagen and elastin (the key proteins of the extracellular matrix in all tissues), AGEs promote high blood pressure, atherosclerosis, and heart failure. In the kidneys, AGEs target nephrons, the filtering units that remove wastes from the blood. (Furber JD, http://www.LegendaryPharma.com/glycation.html, 2007 )

Not only do AGEs wreak havoc on extracellular matrix proteins, they also activate AGE receptors (called RAGEs) on cells throughout the body. RAGEs trigger the release of a wide variety of compounds involved in inflammation and the creation of stiff fibrous tissue, compromising function in the heart, blood vessels, kidneys and brain.

In addition to chronological aging, AGE formation is greatly increased by high blood sugar levels and plays a central role in all diabetes-related disease complications.

AGE accumulation is also accelerated by insulin resistance, high cholesterol, smoking, and a diet lacking in vitamin, mineral and antioxidant-rich fruits and vegetables. In fact, a diet made up of highly processed foods, especially foods processed at high heat, is loaded with AGEs, which our bodies absorb from the food. (Cooper ME. Am J Hypertens. 2004 Dec;17(12 Pt 2):31S-38S.)

Fortunately, test tube, animal and human studies demonstrate that AGE crosslinks can be effectively—and safely—broken by ALT-711 (alagebrium), preventing and reversing AGE-related pathology.(Pizzorno L, ALT711: Cross Link Breaker Delivers Effective Anti-AGE-ing Therapy, http://www.lmreview.com/#AGEs)

In diabetic animals, ALT-711 has been shown to reduce the body’s load of AGEs, promoting AGE excretion in the urine, and to improve the heart muscle’s pumping ability, decrease stiffness in the aorta (the artery through which blood flows into the body from the heart), decrease proteinuria (protein in the urine, a sign of kidney damage), reverse ED (erectile dysfunction) and extend survival. (Bakris GL, et al. Am J Hypertens. 2004 Dec;17(12 Pt 2):23S-30S; Susic D, et al. Curr Opin Cardiol. 2004 Jul;19(4):336-40; Peppa M, et al. Am J Nephrol. 2006;26(5):430-6; Usta MF, et al. J Sex Med. 2006 Mar;3(2):242-50.)

In men who still had high blood pressure (systolic blood pressure >140 mmHg, diastolic blood pressure <90 mmHg or pulse pressure >60 mmHg), even after treatment with antihypertensive drugs, ALT-711 (210 mg twice daily for 8 weeks) decreased arterial stiffness by 37% and reduced blood pressure by an average of 6.8 mmHg. The men’s blood flow (measured by flow-mediated dilation) increased from an average of 4.6 to 7.1, plus levels of a number of compounds that indicate blood vessel damage and thickening greatly decreased. (Zieman SJ, et al. J Hypertens. 2007 Mar;25(3):577-83.)

When given to elderly patients (mean age 71) with diastolic heart failure, ALT-711 (420 mg/day for a period of 16 weeks) significantly decreased left ventricular mass (the major pumping chamber on the left side of the heart). Patients’ quality of life increased almost 25% as measured by the Minnesota Living with Heart Failure assay. (Little WC, et al. J Card Fail. 2005 Apr;11(3):191-5.)

Other recent studies indicate that ALT-711’s multiple benefits are related not only to its ability to break AGE-related crosslinks, but also to its effects on cell receptors (RAGE), which result in lowered oxidative stress (free radical damage) and diminished pro-fibrotic cytokine production. (Coughlan MT, et al. Kidney Int Suppl. 2007 Aug;(106):S54-60.)

In Phase 2 clinical trials involving approximately 800 patients, ALT-711 has been found to be so safe and well-tolerated that it produced fewer side effects than placebo! (Vasan S, Foiles P, et al., Arch. Biochem. Biophys.,2003; Synvista Scientific Publications: http://www.alteon.com/scientific_publications/index.htm)

For all of us as we grow older, but especially for those with diabetes, metabolic syndrome or cardiovascular disease, ALT-711 (alagebrium) offers effective, safe therapy for the prevention, retardation, and reversal of the diseases of AGE-ing.

REFERENCES

Bakris GL, Bank AJ, Kass DA, et al. Advanced glycation end-product cross-link breakers. A novel approach to cardiovascular pathologies related to the aging process. Am J Hypertens. 2004 Dec;17(12 Pt 2):23S-30S.

Cooper ME. Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease. Am J Hypertens. 2004 Dec;17(12 Pt 2):31S-38S.

Coughlan MT, Forbes JM, Cooper ME. Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes. Kidney Int Suppl. 2007 Aug;(106):S54-60.

Furber JD, Legendary Pharmaceuticals, “Background: Glycation and Crosslinking Proteins”, (Revision 2 Oct 2007) http://www.LegendaryPharma.com/glycation.html

Jeyabal PV, Kumar R, Gangula PR, et al. Inhibitors of advanced glycation end-products prevent loss of enteric neuronal nitric oxide synthase in diabetic rats. Neurogastroenterol Motil. 2007 Oct 17 [Epub ahead of print]

Little WC, Zile MR, Kitzman DW, Hundley WG, O’Brien TX, Degroof RC. The effect of alagebrium chloride (ALT-711), a novel glucose cross-link breaker, in the treatment of elderly patients with diastolic heart failure. J Card Fail. 2005 Apr;11(3):191-5.

Peppa M, Brem H, Cai W, et al. Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711). Am J Nephrol. 2006;26(5):430-6. Epub 2006 Sep 13.

Pizzorno L, ALT-711 – Effective New Anti-Aging Therapy, Smart Publications http://www.smart-publications.com

Pizzorno L, ALT-711: Cross Link Breaker Delivers Effective Anti-AGE-ing Therapy, http://www.lmreview.com/#AGEs

Susic D, Varagic J, Ahn J, Frohlich ED. Crosslink breakers: a new approach to cardiovascular therapy. Curr Opin Cardiol. 2004 Jul;19(4):336-40.

Usta MF, Kendirci M, Gur S, et al. The breakdown of preformed advanced glycation end products reverses erectile dysfunction in streptozotocin-induced diabetic rats: preventive versus curative treatment. J Sex Med. 2006 Mar;3(2):242-50; discussion 250-2.

Vasan S, Foiles P, Founds H. Therapeutic potential of breakers of advanced glycation end product-protein crosslinks. Arch Biochem Biophys. 2003 Nov 1;419(1):89-96.

Zieman SJ, Melenovsky V, Clattenburg L, et al. Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension. : J Hypertens. 2007 Mar;25(3):577-83. 278974