Alzheimer's and Parkinson's could be halted by a protein that helps hedgehogs hibernate

Neurological conditions such as Alzheimer’s and Parkinson’s disease can be devastating to both the patient and their loved ones. Due to the progressive nature of the diseases they tend to get worse over time, leading to an ongoing decline in some bodily functions. While there is no cure for either, there are various treatments available.

Dementia

However, new research has found that there is potential to halt both conditions – by using a protein that helps bears and hedgehogs hibernate.

As reported in the EMBO Molecular Medicine journal, the gene therapy also offers hope of treating stroke and accident victims with acute brain injury.

It is based on “cold-shock chemicals” that enable animals to go to sleep for the winter.

They increase levels of a molecule known as RBM3 that protects neurons from damage.

Dementia

In experiments, mice prone to neurodegenerative disease were injected with antisense oligonucleotides (ASOs) – compounds that can target any gene.

This was despite them having been infected with rogue proteins called prions that can lead to dementia, Parkinson’s and CJD (Creutzfeldt-Jakob Disease).

Lead author Professor Giovanna Mallucci, from the University of Cambridge, said: “Essentially, the cold shock protein enables the brain to protect itself – in this case, against the damage to nerve cells in the brain during prion disease.

“Remarkably, we showed that just a single injection with the ASO was sufficient to provide long-lasting protection for these mice, preventing the inevitable progression of neurodegeneration.”

In the early stages of Alzheimer’s, and other neurodegenerative disorders, synapses are lost. This inevitably progresses to whole brain cells dying.

But during hibernation, up to a third of these connections in the brain are culled as the body preserves precious resources over winter, and those connections are reformed in the spring, with no loss of memory.

The international team took a step towards harnessing this power by identifying a key element in the cold shock protein gene which prevents expression under normal conditions. Removing it with an ASO resulted in more RBM3.

Twelve weeks after being administered with disease causing prions, control mice succumbed and showed extensive loss of neurons in the hippocampus which controls memory.

Senior woman confusion

However, the ASO-treated mice had levels of RBM3 twice as high – with extensive preservation of the same brain cells.

Co-author of the study Professor Florian Heyd, from Freie University in Berlin, said: “This approach offers the prospect of being able to protect against diseases such as Alzheimer’s and Parkinson’s, for which we have no reliable preventative treatments.

“We are still a long way off this stage as our work was in mice, but if we can safely use ASOs to boost production of the cold shock protein in humans, it might be possible to prevent dementia.”

He added: “We are already seeing ASOs being used to successfully treat spinal muscular atrophy and they have recently been licensed to treat motor neurone disease.”

Parkinson’s

The number of dementia cases worldwide are expected to triple to more than 150 million by 2050 because of ageing populations.

It is thought that if these findings are replicated in humans, it has potentially major implications for the treatment of patients beyond neurodegeneration.

Common early symptoms of dementia include:

• Memory loss
• Difficulty concentrating
• Finding it hard to carry out familiar daily tasks
• Struggling to follow a conversation or find the right word
• Being confused about time and place
• Mood changes.

The main signs of Parkinson’s disease are:

• Tremors
• Slowness of movement
• Muscle stiffness.