Time to turn science into new treatments
How a new Parkinson’s Virtual Biotech project aims to develop drugs that slow Parkinson’s by combating oxidative stress, which is damaging brain cells.
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The majority of new treatments today come from basic scientific discoveries, which often happen in university laboratories. These discoveries improve our understanding of human conditions like Parkinson’s. However, when a researcher makes a discovery, this is just the start of the journey to developing a new treatment.
But, in Parkinson’s, we may be losing out on opportunities to develop better treatments.
“There are promising scientific discoveries for Parkinson’s that are not being picked up and developed by commercial companies. We believe we can step in here to bring new treatments forward faster.
— Dr Arthur Roach, Director of Research
So earlier this year, we launched a new initiative to fast-track the most promising scientific discoveries to rapidly develop and test treatments with the potential to transform life for people with Parkinson’s.
We’re calling this major new programme of work the Parkinson’s Virtual Biotech because we’ll be acting in the same way as a small biotech company. But unlike commercial biotechs, we will be dedicated to developing new treatments for one condition — Parkinson’s. And now we can announce a brand new research project…
Developing drugs to combat oxidative stress
The first project to be funded through the virtual biotech comes from scientists at the University of Sheffield. And we’ve launched a new £1million virtual biotech company — Keapstone Therapeutics— to develop it.
The Sheffield team, led by Dr Richard Mead, have identified a possible defence system that helps protect brain cells in models of Parkinson’s and other neurodegenerative conditions. They believe activating this defence system may be the key to saving the brain cells affected by Parkinson’s.
The defence system they’ve identified helps protect cells from something called oxidative stress.
What is oxidative stress?
Our bodies constantly produce naturally occurring molecules called free radicals. They are produced simply by our bodies using oxygen in order to live but, left unchecked, these molecules can cause damage to our cells and tissues.
Most of the time our bodies detoxify the free radicals that are produced to protect us from damage. Oxidative stress happens when there are too many free radicals, and is believed to play a key role in the death of brain cells in Parkinson’s.
Protecting cells from oxidative stress
Antioxidants are known to help to protect cells from oxidative stress. And there have been studies to test antioxidants in Parkinson’s, but so far the results have been disappointing.
A different approach to defending the cells from oxidative stress may be more effective. The damage that oxidative stress causes inside cells is similar to that caused in a house by a fire. Fires usually begin quite slowly but once they are blazing are difficult to put out.
The research team want to install ‘sprinklers’ that stop the fire early, rather than calling the antioxidant ‘fire services’ after the fire has already taken hold.
Targeting Nrf2 to stop Parkinson’s
The approach the researchers have been working on involves a protein called Nrf2 that is part of the cells’ own defence against oxidative stress.
If a treatment could be developed to activate Nrf2 it would have the potential to slow or stop the progression of Parkinson’s. But there is a problem — small drug-like molecules that have been shown to activate Nrf2 could be damaging to cells and cannot enter the brain.
Dr Richard Mead has overcome these issues by developing a technique to find small molecules that promote the activity of Nrf2 in a different way. Instead of activating the protein directly, they are looking for molecules that block another protein called KEAP1, which usually sticks to Nrf2 and interferes with it doing its job.
With KEAP1 out of the way, Nrf2 can trigger the cells’ defence against oxidative stress.
The next steps
This project has hit the ground running as the Sheffield scientists have already identified some promising molecules. The next step is to do further testing to identify the molecules with the most promise.
To do this we are working in partnership with Dr Richard Mead, Sheffield University and a company called Sygnature Discovery, who have the chemical expertise needed to carry out this work.
Chemical specialists at Sygnature will tweak the potential molecules to makes hundreds of different molecules with very similar structures. They can then compare these molecules to understand more about how they work and which will most effectively activate the defence system in cells.
At the end of the project, we hope to have generated drug-like molecules that target oxidative stress by activating the Nrf2 pathway, have the correct properties to go forward to intensive safety and effectiveness testing, and later to clinical trials.
Keeping up the momentum — Martin’s story
Martin was diagnosed with Parkinson’s in December 2014 after noticing a twitch in his right ring finger.
Doctors initially carried out tests, but when the results came back negative he put the twitch down to pre-wedding jitters. After his marriage, his finger was still bothering him. And after seeking a second opinion, he was diagnosed with Parkinson’s.
“Having just got married, I was full of optimism and hope for the future — but my diagnosis shattered that. It was a huge shock and was totally devastating at the time.
“What made it harder is that I know the condition will only get worse and current medication can’t stop it. Fortunately, my condition is progressing slowly. But, I’m still concerned that, without better treatment or a cure, I could one day become a burden to my family.
“The current treatments for Parkinson’s are just not good enough. Medication helps with my symptoms, but I’m still not how I used to be. Also, as my symptoms progress, I will have to take increasing doses to cope — which can cause terrible side effects. Some of the drugs for Parkinson’s can even change your behaviour. It can change you as a person. At least at the moment, although I can’t move as easily as I used to, I know I’m still the person I was inside.”
After he was diagnosed, Martin joined Parkinson’s UK’s Research Support Network, which brings together people who are driven to help find a cure and better treatments for the condition.
“Hearing about exciting new research and innovation in treatments is a big help to me. It helps me feel much more optimistic about the future. Parkinson’s UK’s Virtual Biotech programme is particularly encouraging. It’s all about keeping up the momentum of drug development for people with Parkinson’s — making sure that promising research isn’t forgotten and that it’s invested in and taken forward.
“We desperately need more innovative approaches like this to get more drugs into clinical trials and find a cure –or more treatment options — not just for future generations, but for this one.”
During Parkinson’s Awareness Week 2017, we launched the We Won’t Wait campaign — our first public fundraising campaign. It aimed to raise money towards vital research like the Parkinson’s Virtual Biotech, so we can find better treatments and a cure, in years not decades.
Now we need your help to continue the momentum towards developing new treatments faster. It’s not too late to help us stop Parkinson’s in its tracks. Donate £30 today.
Your generous donation will help us deliver new and better treatments, faster. You can discover more about the research we’re funding by visiting parkinsons.org.uk/research.
