Enzyme supply may improve Alzheimer’s condition….

A pioneering drug treatment has revealed that memory function can be restored in mice afflicted with Alzheimer’s disease.

Dr. Michael Shelanski, director of the Alzheimer's Research Center at Columbia University and his colleagues carried out this study. They treated mice whose brains were already clogged with the amyloid plaques. These plaques are responsible for the irreversible brain damage characteristic of the disease. The same drug may, sometime in future, treat humans with late-stage Alzheimer’s.

Destruction of the plaques and prevention of new ones from forming, are the areas where already existing treatments and vaccines work. This recent treatment aims at a different part of the brain and is effective irrespective of the presence or absence of the plaques. The idea is to help brain cells remove unwanted or over-abundant proteins.

There's no way to know if the approach will work in humans, but researchers are hopeful. In essence, "we were able to restart -- or make more efficient -- the garbage disposal function of the cell," said Dr. Shelanski.

The amyloid beta plaque protein, which is abundant in people with Alzheimer’s, when comes in contact with healthy brain cells results in a decrease of the enzyme responsible for protein disposal called ubiquitin C-terminal hydrolase L1 (Uch-L1).

This results in disruption of protein disposal and hence, they got accumulated in the brain cells of the Alzheimer’s patient.

The team provided extra supplies of the missing enzyme to both brain tissues grown in the lab and to mice with the equivalent of Alzheimer’s disease and studied its effect.

Exposure of healthy brain cells to amyloid beta protein results in disruption of neurotransmission. This condition was reversed by the extra supply of the enzyme Uch-L1. This was tested on mice with the rodent equivalent of Alzheimer’s disease. When the enzyme was supplied to the mice through an injection into the abdomen, their memory improved markedly in spite of the presence of plaques.

“We’re hoping that this treatment can help people who have a lot of plaques in their brain already, or perhaps in combination with other compounds that reduce amyloid-beta,” says Shelanski.

But he says that the route of supplying the enzyme is “not ideal”. They are screening several molecules that would enhance the enzyme level and could be given as a pill.

“The approach might work best in people whose brains still contain soluble rather than solid deposits of amyloid beta protein, as disruption of memory formation by the soluble form is reversible”, comments Brian Austen, who studies amyloid protein at St George’s University of London, UK.

“But brain cells damaged by the solid plaque might not be recoverable”, Austen says. “The approach would not help patients get back their missing neurones, but it would prevent any further memory loss.”

The possibility of a potential new drug and new target for Alzheimer’s treatment was acknowledged by the UK Alzheimer’s Society. “Currently, there’s only one type of drug available, and this only stabilises symptoms for a limited period,” said a spokeswoman. “But research on the new approach is still in the early stages [...] so further trials and research are urgently needed.”