A novel biotherapeutic approach to treating neurodegenerative diseases from the gut...

University of Nottingham iGEM 2020

What are neurodegenerative diseases?

Alzheimer's. Parkinson's. Motor neurone disease.

Some of the biggest names that we see in our ageing populations. Neurodegenerative diseases arrive slowly, but leave devastating effects. Often leading to a severely reduced quality of life and then death, the progression of diseases that affect nerve cells can be a long, drawn out road of pain and suffering.

These diseases can all be characterised by:

• - cognitive decline (loss of memory)
• - delayed or uncontrolled motor responses (tremors, reaction time)
• - mood disorders (inappropriate reactions in serious circumstances, hallucinations)

As many of us may have experienced, the effects of neurodegenerative diseases go far beyond the patient. The debilitating symptoms are very visual and emotional to see, especially when it is one of our loved ones that are suffering. Early signs are often slips in memory, as simple as forgetting to carry a key on you (which we can all relate too) but this can quickly progress to getting lost on the way back from the shops and having trouble recognising relatives. When it begins to get serious, anxiety and loss of coordination are common symptoms which can lead to dangerous situations and then require the immediate family to consider very tough decisions. 

"Do I have to put them in a care home? Or can I keep them as comfortable as possible at home where I can care for them? Will I have to take a step back from my job?" - the responsibility of making these great decisions can be overwhelming and family members can be filled with guilt at their choices. It is a horrible situation for all involved and there is no one right or wrong decision.

Is there treatment available?

Currently, there is no cure for many neurodegenerative diseases. In the UK, acetylcholinesterase inhibitors are one way of reducing the symptoms - they work by preventing the breakdown of neurotransmitter acetylcholinesterase, in effect maximising the flow of communication between neurons. Another blocks excess glutamate (another neurotransmitter) in the brain, while some cases may require the use of anti-depressants or anti-hallucinogens. To target mobility or motor reactions, certain drugs may be given that increase the levels of dopamine in the brain although more and more treatments plans are including light exercises and activities to stimulate use of the brain in creative ways such as painting or story-telling to maintain connections and stay healthy.

However, all these drugs come with side effects, side effects that stack and interact in different ways when combined with other drugs. This leads to a slippery slope from the time of diagnosis to suddenly being on a medication plan that requires you to take dozens of pills a day to counteract unwanted side effects while still balancing the clinical effects of the drugs.

What if we could prevent these symptoms before they arrive?

This summer our iGEM team, at the University of Nottingham, have been working on targeting the gut microbiome to secrete a compound called ketone bodies. Ketones have been shown to have beneficial effects on cognition in clinical trials - most recently it is being investigated by top sports research scientists for their athletic enhancing properties. 

Are ketones a wonder drug?

In our next post, we will discuss the research behind the headlines of the ketone and its resurgence into popular diet culture in the form of the 'keto diet'. What are the benefits and how does it act within the body?