Patent Application: US-201313987913-A

Abstract:
new treatments for alzheimer &# 39 ; s disease utilizing gangliosides , glycoproteins , and replacement of non - mutant enzymes and chaperones , as well as enzyme up - regulation accomplished by a number of gene - therapy methodologies .

Description:
the treatment of ad requires the administration of natural glycoproteins and gangliosides or their semi - synthetic derivatives , such as liga20 ( 5 ). liga20 is prepared commercially by fidia research laboratories , abano terme , italy . studies by several investigators indicate that gm1 and liga20 are neuroprotective both in cultured cells [ 6 - 8 ] and in animal models [ 5 , 9 ]. these studies also indicate that liga20 exerts more potent protective effects than gm1 , probably due to its higher membrane permeability . also , radiolabeled gm1 , injected systemically into animals , has been shown to reach neuronal synapses and neuromuscular junctions [ 10 ]. gm1 has been used in human for the treatment of spinal injury [ 11 ], parkinson disease [ 12 ] and ad [ 13 ], and is well tolerated . svennerholm [ 13 ] used of gm1 by intracerebroventricular injection in a limited number of ad patients and claimed some degree of improvement . the treatment utilizes selective gangliosides , administered intra - muscularly or intravenously , to restore neuronal cell dysfunction , prevent cell death and reduces the levels of aggregated amyloid proteins ( plaques ) and phosphorylated tau ( tangles ) in the ad brains . these effects prevent disease progress and restore the functions of the surviving neurons . the gangliosides to be used are either natural or synthetic . natural therapeutic gangliosides that are effective to treat ad include gm1 , gd1 , gt1 and related structures . these products are presently isolated and purified from the sacrificed cattle brains . purified gm1 is dissolved in isotonic salt solution and is used by intravenous or intramuscular routes at total daily concentrations from 10 mg / kg to 50 mg / kg body wait . this treatment for ad is given on daily basis for one week and then repeated every other week . this treatment for ad include molecules that contain silalylated sugars attached to a carrier long chain lipid . as an example , liga20 is used as a solution , intravenously or intramuscularly , at concentrations from 2 to 30 mg / kg . the treatment schedule is similar to that of gm1 . in this example ad is treated by intramuscular or intravenous administration of glycoproteins that carry sialic acid . synthetic sialylated glycoproteins are used to treat ad . these molecules are synthesized by o - linking of sialylated n - acetylgalactosamine ( gainac ) to serine or threonine , components in synthetic peptides . to assure deposition on neuronal cell membranes , the peptide backbones are linked to a long chain fatty acid . an example of this molecule is what has been synthesized in denmark and called flg [ 14 , 15 ]. this 15 amino acid peptide is a derivative of ncam , and has been shown to be protective of brain memory cells . in this discovery , we attach sialylated gainac to serine ( amino acid number 13 in flg ). this modification will increase the beneficial activity of flg five to ten fold . another modification of flg is the attachment of a long chain fatty acid at the end of the molecule ( for example ceramide ). this molecule is considered a glycolipid - glycoprotein hybrid and has therapeutic effects of both molecule families . ad can be treated by up - regulation of the enzymes responsible for ganglioside and glycoprotein synthesis . alzheimer &# 39 ; s disease is caused by decreased synthesis of particular glycoproteins and gangliosides . agents that can increase levels and activity of enzymes involved in synthesis of these molecules would improve neuronal function . in addition to the enzymes themselves , there are molecular chaperones that facilitate enzyme activities . 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