The journey to clinical trials
Biotech company United Neuroscience have ambitious plans to stop neurological conditions through vaccination. Here, they give us an insight into the process of developing such treatments.
The causes of neurological conditions remain largely unknown. But what we do know is that in conditions such as Parkinson’s, brain cells can become clogged up with old or damaged proteins, stopping them from doing their job properly.
In Parkinson’s, the main culprit seems to be a protein called alpha-synuclein which misfolds and forms sticky clumps called Lewy bodies. We don’t completely understand why alpha-synuclein becomes misfolded in Parkinson’s and how this causes problems inside cells. But research has shown that the build-up of alpha-synuclein is thought to spread between cells, increasing its toxic effect.
This has led researchers to target alpha-synuclein to find ways to decrease its toxic effects and potentially slow the progression of Parkinson’s. There are various ways researchers are targeting this protein, including vaccination. The current vaccines in clinical trials for Parkinson’s are featured in a previous blog.
Trials to treatments: vaccines for Parkinson’s
How can vaccines be developed for Parkinson’s? What vaccines are currently in clinical trials?
There’s also another exciting and unique vaccine in development for Parkinson’s. Let’s find out more about how this vaccine works and who is developing it.
Who are they?
United Neuroscience is a pioneering company working on the development of vaccines against neurological conditions. It is a global company with headquarters in Dublin, Ireland and research centres in Taiwan and the United States. They are committed and ambitious in their aims to prevent neurological conditions, including Parkinson’s, from having the chance to develop.
United Neuroscience is interested in targeting alpha-synuclein to find a way to treat and even prevent the condition from developing. They hope to deliver this through the development of an affordable vaccine.
How do their vaccines work?
United Neuroscience wants to train the body to have its own defence against the troublesome proteins that are building up in neurological conditions, including alpha-synuclein in Parkinson’s.
Normally, vaccines are used to attack foreign invaders such as bacteria or viruses in infectious diseases. These vaccines are made up of tiny fragments of the virus or bacteria that cause the illness, but are not enough to make us ill. They allow our bodies to generate an immune response, a defence against the foreign invader. Specialised proteins called antibodies make up part of this defence. Antibodies help identify and mark foreign invaders for destruction, before triggering other cells to come and destroy them.
Antibodies are very clever proteins. As well as being part of the body’s defence system, they also act as the system’s memory. So, if the body is infected with the same foreign invader, it already has the weapons to defend itself.
However, it is more complex and riskier to attack something that isn’t foreign, such as alpha-synuclein building up in the brains of people with Parkinson’s. This is because when we target something that the body recognises as part of itself, it could lead to autoimmunity. This is a misdirected attack from the immune system that can result in the shutdown of ‘healthy’ cells and tissue, having serious consequences.
Scientists have currently taken two different approaches to try and target alpha-synuclein. The first, and most widely used method, involves designing antibodies in the lab that are then injected into the body to help the immune system to identify, and remove the toxic alpha-synuclein protein. This method, in theory, ensures that only the toxic protein is targeted and not the healthy version, avoiding autoimmune reactions. But this method does not trigger the memory function of the immune system, as the antibodies are provided artificially, and the body has not generated them internally. The lack of memory is a drawback of this method because it means that repeated vaccination would be needed to continually target alpha-synuclein.
The second method is similar to a flu vaccination. A small fragment of the virus, or in this case protein, is injected into the body to raise an immune response. The body produces antibodies against the injected fragment and creates a memory of this response. This potentially allows the targeting of alpha-synuclein over a longer period of time. This second method is currently being used by United Neuroscience.
They have created entirely artificial vaccines in the lab able to generate an immune response to target proteins such as alpha-synuclein. Their technology has been developed over the past two decades and is the first of its kind. This approach seems to be a way to overcome the risks associated with the body attacking itself. It also provides a way for the body to develop its own immune defence and memory against these toxic proteins that are building up inside cells.
Vaccine for Parkinson’s
United Neuroscience is developing a vaccine for Parkinson’s called UB-312. This vaccine has been through pre-clinical development and planning and preparation is underway for a phase I trial. They have been working with Parkinson’s UK and people affected by Parkinson’s to help plan the study.
“Targeting alpha-synuclein in Parkinson’s offers a way to complement existing therapies but also holds potential for a way to prevent Parkinson’s.” Hui-Jing Yu
Medical Director at United Neuroscience, Hui-Jing Yu, tells us more about the progress of the Parkinson’s vaccine.
“We are in the process of planning a phase I trial to test UB-312 in healthy volunteers. The aim of this trial will be to find an optimal dose and assess the safety of the vaccine. If successful, we will move into clinical trials in people with Parkinson’s.
“UB-312 is based on the same technology as the Alzheimer’s vaccine and this alongside pre-clinical work makes us confident that phase I trials have a good chance of success.
“Phase I trials are planned in the Netherlands as this was logistically the best location with the best capacity for the trial. We do hope, moving forward, future trials will have research sites in the UK. We have existing collaborations in the UK that should make this possible.”
Why do treatments take so long to develop?
“Producing long-term measurements take time and can be complex. To understand and measure how a potential treatment is changing the progression of a condition takes a lot of time.
“It is really important to invest time in planning a study and working out the logistics. The success of a trial can hinge on these decisions so it is important to get these things right.
“Contracts with research sites can take a lot of time and it is essential that clinical trials meet the regulatory and ethical standards. Finding people to take part can also be time-consuming. It is essential that the study has been well designed to ensure people taking part have been considered and have received quality information and communication. This ensures that the study is efficient and safe and people don’t drop out.
“The success of small initial studies are often hard to measure. This is not helped by the fact that Parkinson’s is a complex condition with multiple factors at play. It is essential to spend time considering how the success of the trial will be measured.
“We believe that the development of our vaccines will speed up the more our company grows in experience. We have learned a lot from developing the Alzheimer’s vaccine, which will speed up the development of the Parkinson’s vaccination UB-312, as it is using the same platform and technology.”
Reflections from some of the Team
Sharon Tamir (Head of Strategic Alliances — United Neuroscience)
“Our platform has potential to target multiple proteins in many conditions. We have the knowledge to make an impact and this is exciting.”
Hui-Jing Yu (Medical Director — United Neuroscience)
“Targeting alpha-synuclein in Parkinson’s offers a way to complement existing therapies but also holds potential for a way to prevent Parkinson’s.
We have a platform where vaccines are economical and efficient and we have lots of experience delivering these studies. We have a clear development plan and are armed with the tools to push forward.”
Huge thanks to Sharon Tamir and Hui-Jing Yu at United Neuroscience.