Promising novel treatment against Alzheimer disease

September 25, 2018, McGill University
Credit: CC0 Public Domain

New research conducted at the Lady Davis Institute (LDI) at the Jewish General Hospital reveals that a novel drug reverses memory deficits and stops Alzheimer disease pathology (AD) in an animal model. Importantly, this drug has already proven to be non-toxic for humans in a clinical setting and could, therefore, be brought quickly to trials in humans against AD. These findings are published today in Nature Communications.

For years, Dr. LeBlanc, Senior Investigator at the LDI and Professor of Neurology and Neurosurgery at McGill University, has strived to identify early neurodegenerative events responsible for age-related loss. Her team discovered that the Caspase-6 enzyme is highly activated in Alzheimer disease brain lesions and associated with loss of memory. She, therefore, pursued the hypothesis that stopping Caspase-6 might provide relief from memory loss and stop progressive dementia. Since there are no specific Caspase-6 inhibitors, the LeBlanc team moved upstream, ultimately discovering that Caspase-1 was responsible for activating Caspase-6.

"This was a significant revelation because Caspase-1 inhibitors had been developed for treating inflammatory diseases," explains Dr. LeBlanc. "Thus, we decided to test the effects of a particular Caspase-1 inhibitor, called VX-765, against memory loss and brain pathologies in a mouse model of Alzheimer disease."

The work, first authored by Dr. Joseph Flores, a research associate in the LeBlanc lab, showed that VX-765 has an unprecedented beneficial effect in Alzheimer mice. The drug rapidly reverses memory loss, eliminates inflammation, and stops Alzheimer's prototypical amyloid peptide accumulation in the mice brains. In addition to being safe for humans at relatively high doses for extended periods of time, it is capable of reaching the brain, a significant challenge in the development of drugs against disorders of the brain.

While Dr. LeBlanc cautions that there is a considerable bridge to cross between the mouse and that of a human, she believes that since her work has first identified the Caspase-1/Caspase-6 neurodegenerative pathway in human neurons and in human Alzheimer brains, there is a chance that this drug will work just as well in humans as it did in mice. Nevertheless, a clinical trial is needed to determine whether the will be beneficial against Alzheimer disease in humans.

Presently, there are no efficient treatments to significantly treat Alzheimer disease, the major affliction in a group of dementias that affect 47.5 million individuals worldwide.

Explore further: Caspase-2 enzyme inhibitor shows promise for ameliorating fatty liver disease

More information: Joseph Flores et al, Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer's disease mouse model, Nature Communications (2018). DOI: 10.1038/s41467-018-06449-x

Related Stories

Caspase-2 enzyme inhibitor shows promise for ameliorating fatty liver disease

September 13, 2018
Researchers at University of California San Diego School of Medicine have discovered using mice and human clinical specimens, that caspase-2, a protein-cleaving enzyme, is a critical driver of non-alcoholic steatohepatitis ...

Untangling a cause of memory loss in neurodegenerative diseases

October 13, 2016
Tauopathies are a group of neurodegenerative disorders, including Alzheimer's disease that are characterized by the deposition of aggregates of the tau protein inside brain cells. A new study reveals that the cutting of tau ...

Study identifies protein that contributes to cognitive decline in Alzheimer's

June 25, 2013
Researchers at Columbia University Medical Center (CUMC) have demonstrated that a protein called caspase-2 is a key regulator of a signaling pathway that leads to cognitive decline in Alzheimer's disease. The findings, made ...

A new look at caspase 12 research

June 1, 2016
Inflammasomes are assemblies that are central to inflammatory responses. Dr. Lieselotte Vande Walle, Daniel Jiménez Fernández and colleagues from Prof. Mo Lamkanfi's group (VIB/UGent) shed new light on the function of caspase ...

Link between inflammatory process and progression of Alzheimer's disease

December 19, 2012
An international team of researchers from the University of Massachusetts Medical School, the University of Bonn and the Center for Advanced European Studies and Research in Germany have shown that a well-known immune and ...

Diabetes drug 'significantly reverses memory loss' in mice with Alzheimer's

January 1, 2018
A drug developed for diabetes could be used to treat Alzheimer's after scientists found it "significantly reversed memory loss" in mice through a triple method of action.

Recommended for you

Hypothesis underpinning dementia research 'flawed'

October 16, 2018
A hypothesis which has been the standard way of explaining how the body develops Alzheimer's Disease for almost 30 years is flawed, according to a University of Manchester biologist.

Study suggests biological basis for depression, anxiety, sleep disturbances in older adults

October 15, 2018
UC San Francisco researchers, in collaboration with the unique Brazilian Biobank for Aging Studies (BBAS) at the University of São Paulo, have shown that the earliest stages of the brain degeneration associated with Alzheimer's ...

Many cases of dementia may arise from non-inherited DNA 'spelling mistakes'

October 15, 2018
Only a small proportion of cases of dementia are thought to be inherited—the cause of the vast majority is unknown. Now, in a study published today in the journal Nature Communications, a team of scientists led by researchers ...

Scientists create new map of brain region linked to Alzheimer's disease

October 8, 2018
Curing some of the most vexing diseases first requires navigating the world's most complex structure—the human brain. So, USC scientists have created the most detailed atlas yet of the brain's memory bank.

Previously unknown genetic aberrations found to be associated with Alzheimer's progression

October 8, 2018
In a large-scale analysis of RNA from postmortem human brain tissue, researchers at the Icahn School of Medicine at Mount Sinai and Columbia University have identified specific RNA splicing events associated with Alzheimer's ...

Periodontal disease bacteria may kick-start Alzheimer's

October 4, 2018
Long-term exposure to periodontal disease bacteria causes inflammation and degeneration of brain neurons in mice that is similar to the effects of Alzheimer's disease in humans, according to a new study from researchers at ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.