Memantine for Huntington's disease ?

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA glutamate receptors. Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest, Ebixa and Abixa by Lundbeck and Memox by Unipharm.

Now researchers from Burnham & University of California have found that, Memantine, which is approved to treat Alzheimer's disease, successfully treated Huntington's disease in a mouse model by preserving normal synaptic electrical activity and suppressing excessive extrasynaptic electrical activity.

Huntington's disease is a hereditary condition caused by a mutated huntingtin gene that creates a misfolded, and therefore dysfunctional, protein. The new research shows that normal synaptic receptor activity makes nerve cells more resistant to the mutant proteins. However, excessive extrasynaptic activity contributed to increased nerve cell death. The research team found that low doses of Memantine reduce extrasynaptic activity without impairing protective synaptic activity.

This finding is of great importance because of the fact that chronic neurodegenerative diseases like Huntington's, Alzheimer's and Parkinson's are all related to protein misfolding and the researchers have shown for the first time that that electrical activity controls protein folding, and if one has a drug that can adjust the electrical activity to the correct levels, one can protect against misfolding and also the research verifies that appropriate electrical activity is protective. They also found that normal synaptic activity was protective. Subsequently, they treated Huntington's disease model mice with both high and low doses of Memantine and found that the low doses were protective by blocking pathological extrasynaptic activity, while high-dose Memantine encouraged disease progression because it also blocked the protective synaptic NMDA receptor activity. Its really good achievement congratulations. After having small clinical trials, larger, international clinical trials are now being planned....


Source : http://www.eurekalert.org/pub_releases/2009-11/bi-rfp111309.php.

Rethinking of Alzheimer's Disease ?

So for the explanation for the Alzheimer's disease is "amyloid hypothesis", i.e., the disease results from of an accumulation of the peptide amyloid beta, the toxic protein fragments that deposit in the brain and become the sticky plaques that have defined Alzheimer's, this hypothesis has been accepted for 100 years. Something new explanation has been provided by George Bartzokis of UCLA professor of psychiatry and he says that a better working hypothesis is the "myelin model". He explains the model in the following lines :

Like insulation around wires, myelin is a fatty sheath that coats our nerve axons, allowing for efficient conduction of nerve impulses. It is key to the fast processing speeds that underlie our higher cognitive functions and encoding of memories. But the lifelong, extensive myelination of the human brain also makes it uniquely vulnerable to damage. The myelin model's central premise is that it is the normal, routine maintenance and repair of myelin throughout life that ultimately initiates the mechanisms that produce degenerative diseases like Alzheimer's. That is, the amyloid-beta peptide and the tau peptide, which is also implicated in Alzheimer's, as well as the signature clinical signs of the disease, such as memory loss and, ultimately, dementia, are all byproducts of the myelin breakdown and repair processes. The pervasive myelination of our brain is the single most unique aspect in which the human brain differs from other species.

Myelin is produced by oligodendrocytes, specialized glial cells that themselves become more vulnerable with age. Myelination of the brain follows an inverted U-shaped trajectory, growing strongly until our 50s, when it very slowly begins to unravel as we age. The myelin that is deposited in adulthood ensheaths increasing numbers of axons with smaller axon diameters and so spreads itself thinner and thinner. As a result, it becomes more susceptible to the ravages of age in the form of environmental and genetic insults and slowly begins to break down faster than it can be repaired.

The exclusive targeting of the amyloid-beta peptide for many years is understandable because the same genes and enzymes involved in controlling myelination and myelin repair are, ironically, also involved in the production of amyloid-beta proteins. Bartzokis' point is that the amyloid beta may actually develop as a result of the natural process of the repair and maintenance of myelin. So the breakdown that leads to Alzheimer's and other age-related brain diseases, such as Parkinson's, may begin much earlier, before the formation of the protein deposits that are used to define these diseases," Bartzokis said. Hope this explanation will lead to new innovative ideas for drug discoverers like rather than targeting amyloid-beta peptide !. Hoping for the better results....

Ref : http://newsroom.ucla.edu/portal/ucla/new-target-for-alzheimer-s-102065.aspx

Gene Therapy Trial To Treat Alzheimer's Disease !

The first study of its kind for the treatment of patients : the phase II study examines the safety and possible benefits of CERE-110. CERE-110 contains a gene and is injected during surgery into a part of the brain affected by Alzheimer's disease.

The gene will instruct brain cells to produce more of a protein, called Nerve Growth Factor or NGF, which helps nerve cells survive and function properly. The transfer of this gene into the brain is a medical technique called gene therapy. Though the goal is to to stop the progression of Alzheimer's disease, its a good move because still there are drugs to be innovated for the complete cure. Congrats Dr. Chris Kalhorn.

Ref : http://explore.georgetown.edu/news/?ID=44677&PageTemplateID=295

New Marker For Alzheimer's Discovered

New Marker For Alzheimer's Discovered

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