Drug restores cells and memories in Alzheimer's mouse models
Yale School of Medicine News Jul 15, 2017
A new drug can restore memories and connections between brain cells in mice with a model of AlzheimerÂs disease, a new Yale–led study suggests.
ÂThe drug completely erased evidence of AlzheimerÂs synapse damage and memory loss in mouse models of the disease, said Stephen Strittmatter, the Vincent Coates Professor of Neurology and senior author of the study appearing July 5 in the journal Cell Reports.
Researchers such as Strittmatter have made significant inroads into understanding the biology of AlzheimerÂs disease, but identifying effective and safe treatments has been difficult. It is known that amyloid–beta peptides, the hallmark of AlzheimerÂs, couple with prion protein at the surface of brain cells and transmit damaging instructions to the interior of the cell. Yale researchers had previously identified a protein on the cell membrane  metabotropic glutamate receptor 5 or mGluR5  as the gateway that helps transmit damage from the coupling.
Previous attempts had been made to target mGluR5, but most drugs also disrupt signaling of glutamate, the most common neurotransmitter in the human brain. The new compound, Silent Allosteric Modulation or SAM (BMS 984923), was created by Bristol Myers Squibb as part of its effort to treat schizophrenia. The drug does not restrict neurotransmitter signaling in culture tissue or living mice, the study found. After four weeks of treatment, memory and synapses linking brain cells had been restored in mice with a model of AlzheimerÂs.
ÂThe drug does not destroy plaques associated with AlzheimerÂs, but allows them to co–exist with neurons, Strittmatter said.
Yale researchers say the next step is to prepare for preliminary trials of the drugÂs effects on humans. YaleÂs Laura T. Haas is lead author of the study. Researchers from Bristol–Myers Squibb Research and Development also contributed to the paper.
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ÂThe drug completely erased evidence of AlzheimerÂs synapse damage and memory loss in mouse models of the disease, said Stephen Strittmatter, the Vincent Coates Professor of Neurology and senior author of the study appearing July 5 in the journal Cell Reports.
Researchers such as Strittmatter have made significant inroads into understanding the biology of AlzheimerÂs disease, but identifying effective and safe treatments has been difficult. It is known that amyloid–beta peptides, the hallmark of AlzheimerÂs, couple with prion protein at the surface of brain cells and transmit damaging instructions to the interior of the cell. Yale researchers had previously identified a protein on the cell membrane  metabotropic glutamate receptor 5 or mGluR5  as the gateway that helps transmit damage from the coupling.
Previous attempts had been made to target mGluR5, but most drugs also disrupt signaling of glutamate, the most common neurotransmitter in the human brain. The new compound, Silent Allosteric Modulation or SAM (BMS 984923), was created by Bristol Myers Squibb as part of its effort to treat schizophrenia. The drug does not restrict neurotransmitter signaling in culture tissue or living mice, the study found. After four weeks of treatment, memory and synapses linking brain cells had been restored in mice with a model of AlzheimerÂs.
ÂThe drug does not destroy plaques associated with AlzheimerÂs, but allows them to co–exist with neurons, Strittmatter said.
Yale researchers say the next step is to prepare for preliminary trials of the drugÂs effects on humans. YaleÂs Laura T. Haas is lead author of the study. Researchers from Bristol–Myers Squibb Research and Development also contributed to the paper.
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