~Alzheimer's Disease, Part 4 - Innovative Drug Strategies

Innovative Drug Strategies
  • Hydergine
  • Piracetam
  • Memantine
  • Nefiracetam
  • Nimodipine
  • Aminoguanidine
Hydergine. Hydergine (ergoloid mesylates) is used in Europe for Alzheimer's disease and other forms of dementia. It acts as a mild vasodilator. A meta-analysis of studies using Hydergine showed modest improvement for Alzheimer's symptoms, but only in dosages of 4-9 mg a day, rather than the typical dose of 3 mg a day. Hydergine increased the number of neuronal synapses and the plasticity of synaptic junctions in a rat study. However, when the dose is translated to human equivalents, about 2000 mg a day would be required and has never been used in humans (Bertoni-Freddari et al. 1987).

In another study, Hydergine decreased hypoxia (a lack of oxygen) in the early stages of Alzheimer's disease but not in the late stages. In a PET scan analysis in multi-infarct dementia (not Alzheimer's patients) and at a dose of 2.4 mg a day, Hydergine showed an improvement on the PET scans (Nagasawa et al. 1990).

A meta-analysis of the published research on hydergine found significant treatment effects in 13 of the trials that met the selection criteria. The overall review was very positive despite the small number of trials (Olin et al. 2000).

Piracetam. Piracetam is a derivative of gamma-aminobutyric acid (GABA) that has been used in European countries for the treatment of memory loss and other cognitive defects.

Several articles have explored the mechanism of piracetam. One study found that piracetam had beneficial effects on the fluidity of membranes from the hippocampus of Alzheimer's disease patients (Eckert et al. 1999). Researchers have proposed that the mechanism of piracetam is due to its ability to alter the properties of cell membranes in the brain (Muller et al. 1999).

A Phase IV study of piracetam in Hungary was conducted on 104 patients with cognitive decline from Alzheimer's disease, cognitive decline of cerebrovascular origin, or both. Nearly all of the five factors of the modified Mini-Mental State Examination significantly increased, especially the factors of memory and concentration-psychomotor speed. Despite this, statistical analysis of the results found no relevant difference between the treatment and control groups. The degree of cognitive improvement was most pronounced in patients with depressive symptoms (Tariska et al. 2000).

Memantine. Memantine is a derivative of an old anti-influenza drug, Amantidine, that has been used for the treatment of dementia in Germany for more than twenty years. Memantine is a non-competitive NMDA (N-methyl-D-aspartate) antagonist that blocks the action of glutamate, which can over-stimulate the nervous system and become toxic to nerve cells. Memantine has yet to be approved by the FDA (Kornhuber et al. 1994; Jain 2000).

Memantine was used to treat patients with moderately severe to severe primary dementia (49% of the Alzheimer type and 51% of the vascular type): 82 patients received 10 mg a day of memantine and 84 received a placebo. A positive response in the Clinical Global Impression of Change (CGI-C) was seen in 73% of those taking memantine, versus 45% for the placebo group, independent of the etiology of dementia. The results in the Behavioral Rating Scale for Geriatric Patients (BGP) subscore "care dependence" were improved 3.1 points under memantine and 1.1 points under placebo (Winblad et al. 1999).

Nefiracetam. One of the features of the Alzheimer brain is a loss of nicotinic acetylcholine receptors. Researchers have proposed that nefiracetam may be useful in Alz-heimer's disease due to its ability to stimulate nicotinic acetylcholine receptors (Nishizaki et al. 2000).

Nimodipine. Nimodipine, a calcium channel blocker, was found to be superior to placebo and Hydergine in Organic Brain syndrome. However, Alzheimer's disease was not differentiated from the other forms of dementia in this study (Grobe-Einsler 1993).

Aminoguanidine. Aminoguanidine could be of value in reducing AGEs (age-associated glycosylation end-products) in Alzheimer's disease. This therapy has shown some promise in small, isolated studies, but requires large clinical trials if merit is to be established with certainty (Ramamurthy et al. 1999).

Innovative Surgery

Dr. Harry S. Goldsmith has developed a revolutionary surgical technique for the treatment of Alzheimer's disease. The technique involves placing a part of the body called the "omentum" directly on the brain. The omentum is a layer of fat and blood vessels that cover the intestines. The omentum has several key factors that make this technique useful. It provokes angiogenesis (new blood vessel growth) and increases choline acetyltransferase, the enzyme responsible for creating acetylcholine (Goldsmith et al. 1973; Goldsmith et al. 1984a; Goldsmith et al. 1984b; Goldsmith 1985; Goldsmith et al. 1987).

Continued . . .

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