New leads on treating dementia and Alzheimer's

A new research study by scientists in Australia and the US provides an explanation for why clinical trials of drugs reducing proteins in the brain that were thought to cause dementia and Alzheimer's have failed. The study has opened the way for potential new treatments with existing drugs. Published online in the journal Human Molecular Genetics, the researchers assembled evidence from a wide range of human studies and animal models of dementia-related diseases to show that inflammation is a major cause, not just a consequence.

They show that many genes linked with dementia regulate our susceptibility and response to inflammatory damage.

"For decades, scientists have thought that dementia and Alzheimer's Disease are caused by protein aggregates forming in the brain. But recent clinical trials of drugs that reduce the aggregates have failed," says project leader Professor Robert Richards, from the University of Adelaide's School of Biological Sciences. He is working in collaboration with the University's Adelaide Medical School and the National Institutes of Health, in the US.

Inflammation has long been known to increase as dementia-related diseases progress, but only now is it identified as the cause. Previously it was thought to act simply to clean up tissue damage caused by the protein aggregates.

"We know that inflammation has different phases - early on it can be protective against a threat by actively degrading it, but if the threat is not removed, then persistent inflammation actually causes cell death," says Professor Richards.

The new work turns previous thinking around. The genetic linkages imply that the inflammation comes first - and the tissue damage second.

"Many genes linked with dementia operate at the level of controlling cellular inflammation. Both internal and external triggers interact with these genes to play a part. Inflammation is the point through which many triggers converge," says Professor Richards.

He likens the brain inflammation to a virus infection. "Inflammation is a very effective defence against foreign agents like viruses. But as we get older and accumulate mutations, our cells can make proteins and DNA products that mimic viruses, and these build up in the system," he says.

"Normally, our cells bar-code their own products to tell them apart from foreign agents. When these bar-codes aren't in place, our cells can't properly distinguish 'self' and 'non-self' trigger molecules. The result is inflammation that escalates and spreads - hence the term autoinflammatory disease."

Certain types of gene mutation cause these systems to fail earlier or more often, and can increase as we age - possibly accounting for age-related increased risk of developing dementia.

The good news is that by reducing some elements of inflammation, it may be possible to reduce dementia symptoms.

"With this new understanding of the disease, we now need to test existing anti-inflammatory drugs for their effectiveness in treating dementia," he says.

Robert I Richards, Sarah A Robertson, Daniel L Kastner.
Neurodegenerative diseases have genetic hallmarks of autoinflammatory disease.
Human Molecular Genetics, ddy139. doi: 10.1093/hmg/ddy139.

Most Popular Now

Top 20 breaking World Pharma News of 2018

World Pharma News proudly presents the top 20 most popular breaking news from 2018. Have a wonderful 2019 New(s) Year filled with health, happiness, and spectacular succe...

FDA approves first treatment for rare blood diseas…

The U.S. Food and Drug Administration today approved Elzonris (tagraxofusp-erzs) infusion for the treatment of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adu...

Bristol-Myers Squibb to acquire Celgene to create …

Bristol-Myers Squibb Company (NYSE:BMY) and Celgene Corporation (NASDAQ:CELG) today announced that they have entered into a definitive merger agreement under which Bristo...

Lynparza meets primary endpoint in Phase III SOLO-…

AstraZeneca and Merck & Co., Inc., Kenilworth, N.J., US (Merck: known as MSD outside the US and Canada) announced positive results from the randomised, open-label, contro...

Pediatric leukemia 'super drug' could be developed…

Northwestern Medicine scientists have discovered two successful therapies that slowed the progression of pediatric leukemia in mice, according to three studies published ...

Researchers uncover new mechanism of gene regulati…

Genes contain all the information needed for the functioning of cells, tissues, and organs in our body. Gene expression, meaning when and how are the genes being read and...

AstraZeneca announces organisational changes

AstraZeneca is today announcing organisational changes to support continued scientific innovation and commercial success in the main therapy areas as the Company enters a...

Tumors backfire on chemotherapy

Some patients with breast cancer receive chemotherapy before the tumor is removed with surgery. This approach, called 'neoadjuvant' therapy, helps to reduce the size of t...

Sandoz and Pear Therapeutics announce US launch of…

Sandoz Inc., a Novartis division, and Pear Therapeutics, Inc., announced today the US commercial launch of reSET-O(TM) for patients with Opioid Use Disorder (OUD). reSET-...

Stopping cancer from recruiting immune system doub…

Cancerous tumors trick myeloid cells, an important part of the immune system, into perceiving them as a damaged part of the body; the tumors actually put myeloid cells to...

Boehringer Ingelheim initiates a collaborative par…

Science 37, an industry leader in virtual clinical trials, and Boehringer Ingelheim announced a technology enterprise collaboration agreement that will support Boehringer...

Pfizer initiates phase 2b/3 clinical trial for PF-…

Pfizer Inc. (NYSE: PFE) announced the initiation of a Phase 2b/3 clinical trial for its oral JAK3 inhibitor, PF-06651600, for the treatment of patients with moderate to s...