Israeli Researchers Stop The Brain From Aging To Prevent Alzheimer’s

Forever young? Neurodegenerative disease, such as Alzheimer’s and Parkinson’s, are most likely to occur in older people. Researchers at the Hebrew University of Jerusalem, alongside an Israeli startup called TyrNovo, have made a major step towards halting these diseases – by essentially stopping the brain from aging.

The researchers, led by Doctor Ehud Cohen, found that TyrNovo’s novel and unique compound, named NT219, selectively inhibits the process of aging in order to protect the brain from neurodegenerative diseases, without affecting lifespan. This is a first and important step towards the development of future drugs for the treatment of various neurodegenerative maladies.

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Human neurodegenerative diseases such as Alzheimer’s, Parkinson’s and Huntington’s diseases share two key features: they stem from toxic protein aggregation and emerge late in life. As humans age, the mechanism regulating protective mechanisms that prevent the manifestation of the toxic proteins start to fail, making the elderly exposed to disease.

From worms, to mice, to men

Cohen’s first breakthrough in this area occurred when he discovered, working with worms, that reducing the activity of the signaling mechanism conveyed through insulin and a hormone called IGF1, constituted a defense against the aggregation of a protein which is mechanistically-linked with Alzheimer’s disease. Later, he found that the inhibition of this signaling route also protected Alzheimer’s-model mice from behavioral impairments and pathological phenomena typical to the disease. In these studies, the path was reduced through genetic manipulation, a method not applicable in humans.

Dr. Hadas Reuveni, the CEO of TyrNovo, a startup company formed for the clinical development of NT219, and Profesor Alexander Levitzki from the Department of Biological Chemistry at the Hebrew University, with their research teams, discovered a new set of compounds that inhibit the activity of the IGF1 signaling cascade in a unique and efficient mechanism, primarily for cancer treatment, and defined NT219 as the leading compound for further development.

Now, in a fruitful collaboration Cohen and Reuveni, together with Cohen’s associates Tayir El-Ami and Lorna Moll, have demonstrated that NT219 efficiently inhibits IGF1 signaling, in both worms and human cells. The inhibition of this signaling pathway by NT219 protected worms from toxic protein aggregation that in humans is associated with the development of Alzheimer’s or Huntington’s disease.

Treating the untreatable

Recently, Cohen’s laboratory obtained an ethical approval to test the therapeutic efficiency of NT219 as a treatment in Alzheimer’s-model mice, hoping to develop a future treatment for neurodegenerative disorders that currently cannot be treated.

Cohen is a member of the Department of Biochemistry and Molecular Biology, at the Institute for Medical Research Israel-Canada in the Hebrew University of Jerusalem’s Faculty of Medicine. The project was funded by the Rosetrees Trust of Britain. The findings were published this week in the journal Aging Cell.

Photo: Brain Aging by Bigstock