Israeli scientists gave an artificial molecule they invented to 30 mice suffering from Alzheimer’s — and found that all of them recovered, regaining full cognitive abilities.
They stress that this was a small sample of mice and that human testing is far off, but believe the result indicates that within a decade, their synthetic molecule could be developed into a drug for treating the degenerative disease.
The peer-reviewed research, led by neuroscientists from Ben-Gurion University, was recently published in the journal Translational Neurodegeneration.
“We are taking a very different approach than efforts at Alzheimer’s medicines that we have seen so far,” Prof. Varda Shoshan-Barmatz, the lead author, told The Times of Israel. “Most are trying to address plaque that forms in the brain, but we are addressing dysfunction elsewhere. And we’re optimistic. Mice who had Alzheimer’s and received our molecule and then underwent tests had the same cognitive abilities as mice who’d never had Alzheimer’s.”
Interestingly, the molecule appears to have been effective without significantly reducing the amount of plaque, which she thinks indicates that scientists may have been overly fixated on the plaque.
There is scientific literature on the dysfunction of mitochondria among people with Alzheimer’s. Mitochondria are organelles — tiny miniature organs within cells — that provide the cell with power. Scientists believe that when they malfunction and fail to produce the normal quantities of energy, it can lead to cell death, inflammation and reduced immune response.
Despite Alzheimer’s being linked to mitochondrial dysfunction, no drug candidates are currently focused on mitochondria. Drug research is mostly concerned with combatting the buildup of protein fragments between nerve cells in the brain, which are thought to be linked to Alzheimer’s.
The Ben-Gurion University team set out to normalize mitochondrial activity by countering the harmful effects that occur when a protein called VDAC1 is over-produced.
The protein plays a crucial role in regulating the metabolic and energetic functions of mitochondria when produced in normal quantities. But the scientists found that it is produced in huge levels in the brains of mice with Alzheimer’s, and interferes with mitochondrial activity.
“In our research, we have shifted the focus of Alzheimer’s treatments from the plaque to this protein, which is produced in the nerve cells around the plaque instead,” said Shoshan-Barmatz. “We prevent this protein from causing cell death, as the molecule interferes with its harmful effect.”
Her team, which included Prof. Shira Knafo, Prof. Alon Monsonego, Prof. Noga Vardi, Dr. Anna Kuzmin-Steinfer and Dr. Ankit Verma, developed a molecule that binds to the VDAC1 protein.
“By binding to the VDAC1, it prevents it from causing neuronal cell death and other changes associated with Alzheimer’s, including neuro-inflammation and neuro-metabolic dysfunctions,” Shoshan-Barmatz said.
To make the molecule, her team searched scientific libraries for compounds that had qualities suggesting that it would interact with VDAC1 and inhibit its harmful effects. They developed one of the compounds into the molecule, which is designed to prevent the changes in the mitochondria.
The molecule was given to 30 mice with Alzheimer’s for a period of five months, dosed via their drinking water. Meanwhile, a similar number of mice with Alzheimer’s didn’t receive the molecule.
“The mice underwent various tests. At the start, they had loss of memory and impaired cognitive ability. But by the end of the experiment, the mice who received the molecule had the same memory and cognitive ability as mice without Alzheimer’s,” said Shoshan-Barmatz.
“Almost no cell death exists in healthy mice. In the mice with Alzheimer’s, there was a massive neuronal cell death. The molecule prevented neuronal cell death and thus other changes associated with Alzheimer’s, including neuroinflammation and neuro-metabolic dysfunctions. The effects were reflected in the prevention of the decline of cognitive skills such as learning and memory in the sick mice,” she said.
When the mice were killed at the end of the experiment, the scientists took the brains and analyzed them. “The brains of mice who went without treatment had suffered from neuron death and therefore there was a reduced court of neurons,” said Shoshan-Barmatz.
“They had poorly functioning metabolism. By contrast, in the brains of mice who had received the treatment, the neurons were present in normal quantities, indicating cell death had been slowed, and the metabolism performed normally.
“We have established a startup company called Tamarix. I hope that this could be developed and used for clinical treatment, but it’s likely to take time — seven to ten years.”