About Hydroxypropyl Beta Cyclodextrin
Hydroxypropyl beta cyclodextrin (HPβCD) is comprised of seven sugar molecules bound together in a ring (cyclic oligosaccharide).
The ring-shaped, three-dimensional structure has a hydrophobic cavity in its center, which is capable of trapping cholesterol and lipids. It has been used extensively as an excipient in the food, deodorant, and drug industry for the past century, and it is generally recognized as safe (GRAS).
As an active ingredient, HPβCD entraps and removes intracellular cholesterol and lipids that can cause injury to the kidneys and other organs, including the brain and liver.
Source: Lopez CA, de Vries AH, Marrink SJ (2011) Molecular Mechanism of Cyclodextrin Mediated Cholesterol Extraction. PLoS Comput Biol 7(3): e1002020. doi:10.1371/journal.pcbi.1002020.
HPβCD has shown promising pre-clinical results in kidney disease. Progression of kidney disease was prevented in mouse models of focal segmental glomerulosclerosis (FSGS)1 and Alport Syndrome (AS)2, and diabetic kidney disease was prevented or partially prevented in two pre-clinical studies3.
Promising pre-clinical results have also been demonstrated in non-renal indications, including Alzheimer’s disease4, atherosclerosis5, non-alcoholic fatty liver disease6, and Stargardt’s disease7. A successful Phase 1 trial has been completed with HPβCD in patients with Niemann Pick, Type C1, an orphan condition associated with lipid accumulation in the brain and liver, and a Phase 2b/3 trial is now underway8.
- Mitrofanova A, Wahl P, Morales X, Correa M, Pedigo C, Ducasa GM, Bruke GW, Merscher S, Kretzler M,Martini S, Fornoni A. Cyclodextrin Protects Podocytes in Focal Segmental Glomerulosclerosis (FSGS). Poster presentation at the Kern Lipid Conference August 3 – 5, 2015, Vail Colorado.
- Morales XA, Mitrofanova AV, David JM, Correa M, Pedigo C, Leclercq F, Varona Santos JT, Mercher S, Fornoni A. Cyclodextrin improves renal function in experimental alport syndrome. Poster presentation at the American Society of Nephrology Kidney Week, November 3-8, 2015, San Diego, CA.
- Merscher-Gomez S, Guzman J, Pedigo CE, Lehto M, Aguillon-Prada R, Mendez A, Lassenius MI, Forsblom C, Yoo T, Villarreal R, Maiguel D, Johnson K, Goldberg R, Nair V, Randolph A, Kretzler M, Nelson RG, Burke GW 3rd, Groop PH, Fornoni A; FinnDiane Study Group. Cyclodextrin protects podocytes in diabetic kidney disease.Diabetes2013 Nov;62(11):3817-27. doi: 10.2337/db13-0399. Epub 2013 Jul 8.
- Yao J, Ho D, Calingasan NY, Pipalia NH, Lin MT, Beal MF. Neuroprotection by cyclodextrin in cell and mouse models of Alzheimer disease.>J Exp Med. 2012 Vol. 209 No. 13 2501-2513.
- Zimmer S, Grebe A, Bakke SS, Bode N, Halvorsen B, Ulas T, Skjelland M, De Nardo D, Labzin LI, Kerksiek A, Hempel C, Heneka MT, Hawxhurst V, Fitzgerald ML, Trebicka J, Björkhem I, Gustafsson JÅ, Westerterp M, Tall AR, Wright SD, Espevik T, Schultze JL, Nickenig G, Lütjohann D, Latz E. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming.Sci Transl Med. 2016 Apr 6;8(333):333ra50. doi: 10.1126/scitranslmed.aad6100.
- Walenbergh SM, Houben T, Hendrikx T, Jeurissen ML, van Gorp PJ, Vaes N, Olde Damink SW, Verheyen F, Koek GH, Lütjohann D, Grebe A, Latz E, Shiri-Sverdlov R. Weekly Treatment of 2-Hydroxypropyl-β-cyclodextrin Improves Intracellular Cholesterol Levels in LDL Receptor Knockout Mice.Int J Mol Sci. 2015 Sep 2;16(9):21056-69. doi: 10.3390/ijms160921056.
- Nociari MM, Lehmann GL, Perez Bay AE, Radu RA, Jiang Z, Goicochea S, Schreiner R, Warren JD, Shan J, Adam de Beaumais S, Ménand M, Sollogoub M, Maxfield FR, Rodriguez-Boulan E. Beta cyclodextrins bind, stabilize, and remove lipofuscin bisretinoids from retinal pigment epithelium. Proc Natl Acad SciU S A. 2014 Apr 8;111(14):E1402-8. doi: 10.1073/pnas.1400530111. Epub 2014 Mar 24.
- Vtesse Inc. Press Release, May 23, 2016.