Immune cells against Alzheimer's?

Scientists at the German Center for Neurodegenerative Diseases (DZNE), the Ludwig-Maximilians-Universitaet (LMU) Munich and Denali Therapeutics (South San Francisco, CA, USA) have developed an approach to stimulate immune cells of the brain in such a way that they might possibly provide better protection against Alzheimer's disease. Their report has been published in the journal EMBO Molecular Medicine. These findings could ultimately enable development of novel therapies to treat Alzheimer's disease.

The researchers identified a specific antibody that binds to the brain's immune cells, termed "microglia". This stimulates their activity in such a way that they live longer, divide more quickly and detect aberrant substances more easily. In mice with disease symptoms resembling those of Alzheimer's, studies revealed that deposits of proteins (called "plaques") were recognized and degraded more quickly. The notorious plaques are among the hallmarks of Alzheimer's disease, and are suspected to cause neuronal damage.

"We found that the plaques were not removed in their entirety, but rather this happened to their periphery. It is assumed that it is precisely this border area that repeatedly releases proteins which cause damage to neurons. So we may have found a way to specifically remove particularly harmful forms of amyloid, which is the protein contained in the plaques," said Prof. Christian Haass, speaker of the DZNE's Munich site and a department head of the LMU's Biomedical Center Munich.

Immune cells of the brain

Haass and colleagues have been focusing on the immune cells of the brain for quite some time. Their research focuses on TREM2, a so-called receptor on the cell surface to which other molecules can attach. TREM2 can occur in different versions from person to person - some of these altered versions drastically increase the risk of developing Alzheimer's in old age. In previous studies, the Munich researchers found that these special variants put the microglia into an irreversible dormant state, which prevents the immune cells from functioning properly to recognize, absorb and break down plaques and dead cells. "Conversely, we suspect that activation of the microglia could help to eliminate plaques and thus combat Alzheimer's. TREM2 seems to play an important role in this process. The receptor apparently helps to switch the microglia from dormant to active mode," the Munich scientist said.

This is precisely the approach the Munich team and Denali are pursuing. The antibody identified, which is now generated using biotechnological methods, binds to TREM2, thereby triggering processes that enhance microglia activity.

However, the Munich-based biochemist cautioned that further studies are required prior to progressing this approach to clinical trials: "We have shown that immune cells can be stimulated to break down amyloid deposits more effectively. This demonstrates that our approach can work in principle. However, there is still a long way to go before it can be tested in humans and additional data is necessary to validate this approach."

Search for new therapeutic approaches

Current therapies can alleviate the symptoms of Alzheimer's to some extent, but they cannot stop the disease from progressing. "So far, all attempts to treat Alzheimer's effectively have been unsuccessful. Just recently, a clinical trial with two drugs failed. Although there is another experimental agent that seems to have a positive effect on memory, it remains to be seen whether this drug will be approved by regulatory authorities. In view of this situation, innovative therapeutic approaches are urgently needed. This is precisely the aim of our research", said Haass.

Kai Schlepckow, Kathryn M Monroe,Gernot Kleinberger, Ludovico Cantuti‐Castelvetri, Samira Parhizkar, Dan Xia, Michael Willem, Georg Werner, Nadine Pettkus, Bettina Brunner, Alice Sülzen, Brigitte Nuscher, Heike Hampel, Xianyuan Xiang, Regina Feederle, Sabina Tahirovic, Joshua I Park, Rachel Prorok, Cathal Mahon, Chun‐Chi Liang, Ju Shi, Do Jin Kim, Hanna Sabelström, Fen Huang, Gilbert Di Paolo, Mikael Simons, Joseph W Lewcock, Christian Haass.
Enhancing protective microglial activities with a dual function TREM2 antibody to the stalk region.
EMBO Mol Med, 2020. doi: 10.15252/emmm.201911227.

Most Popular Now

AstraZeneca to donate 9 million face masks to supp…

AstraZeneca is donating nine million face masks to support healthcare workers around the world as they respond to the COVID-19 (novel coronavirus) global pandemic. AstraZ...

Singapore modelling study estimates impact of phys…

A new modelling study conducted in a simulated Singapore setting has estimated that a combined approach of physical distancing [2] interventions, comprising quarantine (f...

Roche response to COVID-19 pandemic

Roche Group (SIX: RO, ROG; OTCQX: RHHBY), provided an update on the various actions the company is taking to address the COVID-19 pandemic. On March 19, 2020, Roche co...

Amgen and the Amgen Foundation commit up to $12.5 …

Amgen (NASDAQ:AMGN) and the Amgen Foundation announced an initial commitment of up to $12.5 million to support U.S. and global relief efforts to address critical needs in...

CAR macrophages go beyond T cells to fight solid t…

Chimeric antigen receptor (CAR) T cell therapy has been a game-changer for blood cancers but has faced challenges in targeting solid tumors. Now researchers from the Pere...

Novartis and life sciences companies commit expert…

Novartis and a consortium of life sciences companies announced an important collaboration to accelerate the development, manufacture and delivery of vaccines, diagnostics...

Vivli to launch a portal for sharing data from COV…

In a visible sign of data sharing leadership, Vivli, the Center for Clinical Research Data has committed to serving the open science community through the launch of a COV...

Roche initiates Phase III clinical trial of Actemr…

Roche (SIX: RO, ROG; OTCQX: RHHBY) is working with the Food & Drug Administration (FDA) to initiate a randomised, double-blind, placebo-controlled Phase III clinical tria...

Novartis commits to donate up to 130 million doses…

Novartis announced its commitment to donate up to 130 million doses of generic hydroxychloroquine to support the global COVID-19 pandemic response. Hydroxychloroquine and...

Understanding how COVID-19 affects children vital …

Though COVID-19 so far appears to be largely sparing children, researchers are cautioning that it is critical to understand how the virus affects kids to model the pandem...

Favipiravir flu drug 'clearly effective' in treati…

According to the multiple news articles the drug favipiravir (sold under the brand name Avigan), developed by Fujifilm Toyama Chemical, had produced encouraging outcomes ...

Free EDC software for non-profit COVID-19 related …

Italy-based EDC provider, Nubilaria srl, offers its ACTide EDC pro-bono for European non-profit COVID-19 Coronavirus related studies. The platform is made available for t...