Early manifestations of dementing illness: Treatment with glycosaminoglycan polysulfate

Glycosaminoglycan Polysulfate in Primary Degenerative Dementia

“…This might be explained by the small sample size and the short -30 days -duration of drug administration. The same might also explain the dif ference between the clinical findings in this study and the results of other clinical investigations [7,24].…”

“…It is a heparin-relat ed substance with 'heparinoid' activity [1] and inhibiting effect on the aortic uptake of low-density lipoproteins [2,3] and on arterial smooth muscle cell growth -as docu mented in vitro [4], In a series of systematic preclinical pharmacologic stud ies it was revealed that the heparinoid activity of G A P was below the level which could have a clinically significant effect on blood coagulation, whereas the inhibiting effect of G A P on the uptake of low-density lipoproteins was suffi ciently strong to produce regression of atherosclerotic lesions in experimental animals (rabbit) [5,6], The therapeutic effects of G A P in elderly patients with the diagnosis of multi-infarct dementia (MID) were sup ported by findings in multicenter clinical investigations [7,8]. The same studies also revealed that the therapeutic changes with G A P extended beyond M ID and included primary degenerative dementia of the Alzheimer type (PDD).…”

Glycosaminoglycan Polysulfate in Primary Degenerative Dementia

“…This might be explained by the small sample size and the short -30 days -duration of drug administration. The same might also explain the dif ference between the clinical findings in this study and the results of other clinical investigations [7,24].…”

“…It is a heparin-relat ed substance with 'heparinoid' activity [1] and inhibiting effect on the aortic uptake of low-density lipoproteins [2,3] and on arterial smooth muscle cell growth -as docu mented in vitro [4], In a series of systematic preclinical pharmacologic stud ies it was revealed that the heparinoid activity of G A P was below the level which could have a clinically significant effect on blood coagulation, whereas the inhibiting effect of G A P on the uptake of low-density lipoproteins was suffi ciently strong to produce regression of atherosclerotic lesions in experimental animals (rabbit) [5,6], The therapeutic effects of G A P in elderly patients with the diagnosis of multi-infarct dementia (MID) were sup ported by findings in multicenter clinical investigations [7,8]. The same studies also revealed that the therapeutic changes with G A P extended beyond M ID and included primary degenerative dementia of the Alzheimer type (PDD).…”

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

“…At clinical and experimental level, this increase of PAI-1 with decreased proteolytic activity is normalized with the restoration of cellular GSH synthesis [50]. It suggests possible benefits with treatments with PAI-1 inhibitors [260]- [264], such as glycosaminoglycans [265] [266], sulodexide [258] [267], GSH administration at systemic level to normalize the cell concentration [268] [269] or with their precursors to activate the GSH synthesis at cerebral level [270] [271]. It is possible that cerebral mechanisms of GSH and fibrinolysis/ ß-amyloidosis, can be fundamental pillars in the prevention of aging pathology (TED, MS, T2DM and AD).…”

Practice parameter: Management of dementia (an evidence-based review) [RETIRED]

“…74 Treatment with various formulations of gingko biloba was associated with significant improvements in some (but not all) a priori parameters including a small treatment-placebo difference on a cognitive measure (not detected on a clinical global), 75 some improvement on a clinician's global assessment and an activities of daily living scale, 76 and increased speed on a subset of timed tasks. 77 Several other agents including glycosamine 78 nimodipine, 79 pyritonol, 80 and acetyl-L-carnitine 81 all have shown small improvements in overall functioning in populations with patients with mixed dementia, but none proved a treatment benefit on all the primary outcome measures.…”

Glycosaminoglycan Polysulfate in Primary Degenerative Dementia

“…This might be explained by the small sample size and the short -30 days -duration of drug administration. The same might also explain the dif ference between the clinical findings in this study and the results of other clinical investigations [7,24].…”

“…It is a heparin-relat ed substance with 'heparinoid' activity [1] and inhibiting effect on the aortic uptake of low-density lipoproteins [2,3] and on arterial smooth muscle cell growth -as docu mented in vitro [4], In a series of systematic preclinical pharmacologic stud ies it was revealed that the heparinoid activity of G A P was below the level which could have a clinically significant effect on blood coagulation, whereas the inhibiting effect of G A P on the uptake of low-density lipoproteins was suffi ciently strong to produce regression of atherosclerotic lesions in experimental animals (rabbit) [5,6], The therapeutic effects of G A P in elderly patients with the diagnosis of multi-infarct dementia (MID) were sup ported by findings in multicenter clinical investigations [7,8]. The same studies also revealed that the therapeutic changes with G A P extended beyond M ID and included primary degenerative dementia of the Alzheimer type (PDD).…”

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

“…At clinical and experimental level, this increase of PAI-1 with decreased proteolytic activity is normalized with the restoration of cellular GSH synthesis [50]. It suggests possible benefits with treatments with PAI-1 inhibitors [260]- [264], such as glycosaminoglycans [265] [266], sulodexide [258] [267], GSH administration at systemic level to normalize the cell concentration [268] [269] or with their precursors to activate the GSH synthesis at cerebral level [270] [271]. It is possible that cerebral mechanisms of GSH and fibrinolysis/ ß-amyloidosis, can be fundamental pillars in the prevention of aging pathology (TED, MS, T2DM and AD).…”

Practice parameter: Management of dementia (an evidence-based review) [RETIRED]

“…74 Treatment with various formulations of gingko biloba was associated with significant improvements in some (but not all) a priori parameters including a small treatment-placebo difference on a cognitive measure (not detected on a clinical global), 75 some improvement on a clinician's global assessment and an activities of daily living scale, 76 and increased speed on a subset of timed tasks. 77 Several other agents including glycosamine 78 nimodipine, 79 pyritonol, 80 and acetyl-L-carnitine 81 all have shown small improvements in overall functioning in populations with patients with mixed dementia, but none proved a treatment benefit on all the primary outcome measures.…”

Glycosaminoglycan Polysulfate in Primary Degenerative Dementia

“…This might be explained by the small sample size and the short -30 days -duration of drug administration. The same might also explain the dif ference between the clinical findings in this study and the results of other clinical investigations [7,24].…”

“…It is a heparin-relat ed substance with 'heparinoid' activity [1] and inhibiting effect on the aortic uptake of low-density lipoproteins [2,3] and on arterial smooth muscle cell growth -as docu mented in vitro [4], In a series of systematic preclinical pharmacologic stud ies it was revealed that the heparinoid activity of G A P was below the level which could have a clinically significant effect on blood coagulation, whereas the inhibiting effect of G A P on the uptake of low-density lipoproteins was suffi ciently strong to produce regression of atherosclerotic lesions in experimental animals (rabbit) [5,6], The therapeutic effects of G A P in elderly patients with the diagnosis of multi-infarct dementia (MID) were sup ported by findings in multicenter clinical investigations [7,8]. The same studies also revealed that the therapeutic changes with G A P extended beyond M ID and included primary degenerative dementia of the Alzheimer type (PDD).…”

Aging: Thromboembolic Disease, Metabolic Syndrome, Type 2 Diabetes Mellitus, and Alzheimer’s Disease

“…At clinical and experimental level, this increase of PAI-1 with decreased proteolytic activity is normalized with the restoration of cellular GSH synthesis [50]. It suggests possible benefits with treatments with PAI-1 inhibitors [260]- [264], such as glycosaminoglycans [265] [266], sulodexide [258] [267], GSH administration at systemic level to normalize the cell concentration [268] [269] or with their precursors to activate the GSH synthesis at cerebral level [270] [271]. It is possible that cerebral mechanisms of GSH and fibrinolysis/ ß-amyloidosis, can be fundamental pillars in the prevention of aging pathology (TED, MS, T2DM and AD).…”

Practice parameter: Management of dementia (an evidence-based review) [RETIRED]

“…74 Treatment with various formulations of gingko biloba was associated with significant improvements in some (but not all) a priori parameters including a small treatment-placebo difference on a cognitive measure (not detected on a clinical global), 75 some improvement on a clinician's global assessment and an activities of daily living scale, 76 and increased speed on a subset of timed tasks. 77 Several other agents including glycosamine 78 nimodipine, 79 pyritonol, 80 and acetyl-L-carnitine 81 all have shown small improvements in overall functioning in populations with patients with mixed dementia, but none proved a treatment benefit on all the primary outcome measures.…”