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Saturday 23 February 2019
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New drug target 'can stop debilitating MS'

A potential new drug target for multiple sclerosis (MS) may prevent physical disability associated with the disease.

The research, which was led by Fabrizio Giuliani from the University of Alberta, USA, was published in the Journal of Immunology and focused upon granzyme B's ability to kill neurons in the second phase of MS.

“If we prevent granzyme B from entering neurons, we can also prevent the killing of neurons," Giuliani explained.

"It is this loss of brain cells, in the long-term, which induces disability in those with MS. This is a new drug target for MS that is specific for the neurodegenerative processes following inflammation."

Co-author Chris Bleackley made an earlier discovery about how granzyme B enters target cells through the receptor M6PR. Another faculty researcher discovered that the M6PR receptor is found mostly in neurons.

"We were just connecting the dots and said: 'OK, if this receptor is expressed in neurons specifically and not expressed in other cells, is it possible that this is the mechanism that allows this granzyme B to get into human neurons and start killing brain cells?'" explained Giuliani.

“What we found out is yes, this death receptor allows this specific molecule to get in. If you block the receptor, you also block the neurotoxic effect in neurons. This is an excellent example of collaboration with other researchers and translational research."

Many existing MS treatments primarily target brain inflammation - very effective in the first phase of the disease but not as helpful once patients reach the second phase.
Giuliani believes new medications are needed that can either repair inflamed brain cells or prevent brain degeneration in the first place.

This newly discovered drug target could open the door to new medications that do just that – prevent brain cell death in the early stages of the disease.

With this drug target, only a specific function of a cell would be blocked, not multiple functions of a cell, he said.

Many medications currently on the market block multiple functions of a specific type of cell.

"We are blocking a specific function, not multiple pathways and eventually this strategy could reduce the side effects of new drugs," concluded Giuliani.

Journal of Immunology

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