Approved antibiotic could treat frontotemporal dementia

A readily available antibiotic drug therapy that happens to promote the expression of a certain neurotransmitter receptor could one day be a means of combatting frontotemporal dementia (FTD), officials from the University of Alabama Birmingham announced Dec. 3.

There currently are no viable treatments for the neurodegenerative disease. UAB researchers including Erik Roberson, MD, PhD, associate professor in the deparment of neurology, are focusing on preclinical genetic mutations associated with tau proteins, which play a major role in neurodegenerative disease.

Mouse models expressing human tau with the genetic mutation and were found to have deteriorated function of key neural networks and synapses, as well as marked symptoms of FTD, including but not limited to compulsions like over-grooming.

The researchers are targeting these symptoms by altering N-methyl-D-aspartate (NMDA) receptor regulation, which, among other things, controls synaptic plasticity and memory function

“We found that mutant tau impairs synapses — the connections between neurons — by reducing the size of the anchoring sites of an essential glutamate receptor called NMDA,” said Roberson in the press release. “Reduction of the anchoring sites left fewer NMDA receptors available at the synapse to receive excitatory signals, thus limiting synaptic firing and network activity.”

Researchers turned to an FDA-approved antibiotic drug, cycloserine, to up-regulate NMDA in mice. This led to significantly better network function and synaptic firing in the preclinical study. Behavioral symptoms were also improved. The next step would be to test whether driving up NMDA function could work similarly for humans. Cycloserine could be assessed in a later-stage clinical trial to that effect.

“This study provides mechanistic insight into how a tau mutation affects specific brain regions to impair a network,” said Roberson. “It also provides a potential therapeutic target, the NMDA receptor, which appears to correct the network and behavioral abnormalities.”