Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Study Leads to Alzheimer's Breakthrough

Published: Thursday, October 10, 2013
Last Updated: Thursday, October 10, 2013
Bookmark and Share
Researchers at the Medical Research Council Toxicology Unit have used an orally-administered compound to block a major pathway leading to brain cell death in mice, preventing neurodegeneration.

The team had found previously that the build up of misfolded proteins in the brains of mice with prion disease over-activates a natural defence mechanism in cells, which switches off the production of new proteins. This mechanism would normally switch back ‘on’ again, but in these mice the continued build-up of misshapen protein keeps the switch turned ‘off’. This is the trigger point leading to brain cell death, as the key proteins essential for nerve cell survival stop being made. 

Originally, the team injected a protein that blocked the ‘off’ switch of the pathway into a small region of the brain, and by doing this were able to restore protein production, and halt the neurodegeneration. The brain cells were protected, and protein levels and synaptic transmission (the way in which brain cells signal to each other) were restored allowing the mice to live longer. This led the scientists to predict that compounds able to block this pathway would also protect brain cells.

In the new study, published in Science Translational Medicine, the researchers gave by mouth a drug-like compound against the pathway to prion infected mice, hoping to block the off-switch in the same way.  The compound, which had originally been developed by GlaxoSmithKline for a different purpose, was able to enter the brain from the bloodstream and halt the disease, throughout the whole brain. However, this compound, despite protecting the brain, also produced weight loss in the mice and mild diabetes, due to damage to the pancreas.*

The researchers studied mice with prion disease because these mouse models currently provide the best animal representation of human neurodegenerative disorders in which the build up of misshapen proteins is linked with brain cell death.  These include Alzheimer’s and Parkinson’s as well as prion diseases.  Another paper in Nature Neuroscience last month highlighted this pathway as a potential therapeutic target in treating Alzheimer’s.

Professor Giovanna Mallucci, who led the team, said, “Our previous study predicted that this pathway could be a target for treatment to protect brain cells in neurodegenerative disease.  So we administered a compound that blocks it to mice with prion disease. We were extremely excited when we saw the treatment stop the disease in its tracks and protect brain cells, restoring some normal behaviours and preventing memory loss in the mice.

“We’re still a long way from a usable drug for humans – this compound had serious side effects. But the fact that we have established that this pathway can be manipulated to protect against brain cell loss first with genetic tools and now with a compound, means that developing drug treatments targeting this pathway for prion and other neurodegenerative diseases is now a real possibility.”

Professor Hugh Perry, chair of the Medical Research Council's Neuroscience and Mental Health Board, said, “Misshapen proteins in prion diseases and other human neurodegenerative disorders, such as Alzheimer’s and Parkinson’s, also over-activate this fundamental pathway controlling protein synthesis in the brains of patients. Despite the toxicity of the compound used, this study indicates that, in mice at least, we now have proof-of-principle of a therapeutic pathway that can be targeted. This might eventually aid the development of drugs to treat people suffering from dementias and other devastating neurodegenerative diseases.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

A Fundamental Protection Mechanism Against Formalin In Mammals is Revealed
Formaldehyde, or formalin, is well known to all of us as a common chemical used in many industrial processes and also as a preservative, remarkably we also produce formaldehyde in our bodies.
Wednesday, September 30, 2015
AstraZeneca, MRC Collaboration to Create New Centre for Early Drug Discovery
The Companies today announced the groundbreaking collaboration aimed at better understanding the mechanisms of human disease. The collaboration will see the creation of a joint research facility at AstraZeneca’s new R&D centre in Cambridge in the UK.
Monday, March 31, 2014
A Declaration of Openness in Using Animals in Research
The MRC and other members of the research sector have signed a declaration on transparency in animal research.
Monday, October 22, 2012
Brain Chemical Finding could Open Door to new Schizophrenia Drugs
New research has linked psychosis with an abnormal relationship between two signalling chemicals in the brain.
Friday, October 01, 2010
Medical Research Council Technology and Pharmidex Announce Drug Discovery Collaboration
Pharmidex to provide all in vivo ADME/PK drug discovery support to the MRCT in 2010.
Thursday, April 15, 2010
Health Protection Agency Launches new Research Centre for Studying Nanotoxicology
The Agency is collaborating with universities and the MRC Toxicology Unit to study the possible health effects of human exposure to nanoparticles.
Friday, July 25, 2008
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Gut Microbes Signal to the Brain When They're Full
Don't have room for dessert? The bacteria in your gut may be telling you something.
Personalized Drug Screening for Multiple Myeloma Patients
A personalized method for testing the effectiveness of drugs that treat multiple myeloma may predict quickly and more accurately the best treatments for individual patients with the bone marrow cancer.
Nanocarriers May Carry New Hope for Brain Cancer Therapy
Berkeley lab researchers develop nanoparticles that can carry therapeutics across the brain blood barrier.
Cancer-Fighting Tomato Component Traced
The metabolic pathway associated with lycopene, the bioactive red pigment found in tomatoes, has been traced by researchers at the University of Illinois.
Batten Disease may Benefit from Gene Therapy
NIH-funded animal study suggests one-shot approach to injecting genes.
Shedding Light on “Dark” Cellular Receptors
UNC and UCSF labs create a new research tool to find homes for two orphan cell-surface receptors, a crucial step toward finding better therapeutics and causes of drug side effects.
Molecule Proves Key to Brain Repair After Stroke
Scientists found that a molecule known as growth and differentiation factor 10 (GDF10) plays a key role in repair mechanisms following stroke.

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos