[Editors] MIT: 'Cocktail' of compounds improves brain function in rodents

[Elizabeth Thomson]

MIT News Office
Massachusetts Institute of Technology
Room 11-400
77 Massachusetts Avenue
Cambridge, MA  02139-4307
Phone: 617-253-2700
http://web.mit.edu/newsoffice/www

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MIT: 'Cocktail' of compounds improves brain function in rodents

--Treatment undergoing a clinical study in Alzheimer's patients

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For Immediate Release
MONDAY, NOV. 26, 2007
Contact: Elizabeth A. Thomson, MIT News Office -- Phone: 617-258-5402  
-- Email: thomson at mit.edu

CAMBRIDGE, Mass.--MIT researchers have shown that a cocktail  
containing three compounds normally in the blood stream promotes  
growth of new brain connections and improves cognitive function in  
rodents. The treatment is now being tested in Alzheimer's patients  
and could hold promise for other brain diseases and injuries.

The mixture, which includes a type of omega-3 fatty acid, is part of  
a new approach to attacking Alzheimer's. That approach focuses on  
correcting the loss of synapses, or connections between neurons,  
which characterizes the disease.

For the past 30 years, researchers have tried targeting the clumps of  
misfolded proteins, known as amyloid beta plaques, found in the  
brains of Alzheimer's patients. However, that approach has not  
yielded any effective treatments for the disease, which affects an  
estimated four million to five million Americans.

“It's been very frustrating,” said Richard Wurtman, the Cecil H.  
Green Distinguished Professor of Neuropharmacology and senior author  
of a paper on the new work published in the November issue of Brain  
Research. “Nobody has demonstrated that if you prevent formation of  
the amyloid, people get better.”

In December, a group of Alzheimer's researchers, including Wurtman,  
will participate in a symposium with the goal of developing a public  
policy to promote new approaches to Alzheimer's research. Organizers  
of the symposium believe that the current system of dementia research  
is “broken” and needs to be fixed.

Alzheimer's researchers agree that the cognitive decline seen in  
Alzheimer's patients is caused by loss of brain synapses. Wurtman and  
others theorize that restoring some of those synapses could provide  
an effective treatment, analogous to giving L-dopa to Parkinson's  
patients. Such treatments don't cure the disease but can restore  
significant brain function, said Wurtman.

Synapses, where information is passed between neurons, play a  
critical role in learning and memory. Messages travel from a  
presynaptic neuron to a postsynaptic cell.

In the Brain Research paper, the MIT team reported that rodents given  
a cocktail of DHA (a type of omega-3 fatty acid), uridine and choline  
showed a greatly increased concentration of dendritic spines, which  
receive messages in the postsynaptic neuron. That indicates that  
synapse regeneration has occurred, which is unusual, Wurtman said.

Synapse regrowth could also prove an effective treatment for other  
brain diseases, such as Parkinson's, or for brain injuries, he said.

The researchers found that rodents who received the treatment  
performed much better on tests of cognitive ability (specifically,  
navigating a water maze). Sarah Holguin, an MIT graduate student in  
brain and cognitive sciences, presented those results at the Society  
for Neuroscience annual meeting earlier this month.

Some of the rats in the studies received all three compounds and some  
received only one. The improvements in synapse growth and cognitive  
ability were greatest in the rats given all three.

Omega-3 fatty acids are not produced in the body but are found in a  
variety of sources, including fish, eggs, flaxseed and meat from  
grass-fed animals. Choline can be synthesized in the body and  
obtained through the diet; it is found in meats, nuts and eggs.  
Uridine cannot be obtained from food sources, but is a component of  
human breast milk and can be produced in the body.

The cocktail of compounds is now in clinical studies in Europe.

Other authors of the Brain Research paper were Toshimasa Sakamoto,  
the first author and a research affiliate in the Department of Brain  
and Cognitive Sciences (BCS), and Mehmet Cansev, a BCS postdoctoral  
associate.

The research was funded by the National Institutes of Health and the  
Center for Brain Sciences and Metabolism Charitable Trust.

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Written by Anne Trafton, MIT News Office