Following the path to a new drug, together

Research looking to find a way to slow or stop Parkinson’s is high on the agenda for people with Parkinson’s, their friends and loved ones. We often hear how frustratingly slow people find research, but there’s a glimmer of hope. Global initiatives to form collaborations to ensure promising treatments are delivered in years and not decades are becoming part of the research landscape.

One such initiative is the Parkinson’s Virtual Biotech, set up by us at Parkinson’s UK, and now a global initiative to make sure projects with the greatest potential to transform life for people with Parkinson’s are invested in and accelerated through the research pipeline. The projects range from those developing drugs to those already testing promising new treatments in clinical trials.

In this blog, we’ll focus on the journey of a particular project that holds great potential to find a way to slow the loss of brain cells in Parkinson’s. Something that no current treatment can do. The journey took off in 2019 when we announced a partnership through the Parkinson’s Virtual Biotech with the Stevenage-based drug discovery company NRG Therapeutics Ltd. We invested nearly £1m, to work towards identifying new molecules that could enter the brain and protect the energy producing part of the cells, known as the mitochondria. 

Now, this project has attracted further global investors, including further contributions from the Parkinson’s Virtual Biotech, attracting a total of £16 million to complete the necessary steps to prepare for clinical trials. This shows the power of the Parkinson’s Virtual Biotech and the value that charity investment can bring when looking to accelerate drug discovery.

What’s the drug hoping to do?

Help with faulty power supplies

Researchers believe one contributing factor to the loss of dopamine producing cells in Parkinson’s is faulty or dysfunctional mitochondria. Mitochondria are present in almost all types of cells in the body. They act like batteries, providing energy to the cell so it can carry out its job. They do this by converting nutrients from food and oxygen into a universal energy source known as adenosine triphosphate, or ATP.

Dopamine producing cells, which are lost throughout the progression of Parkinson’s, are particularly active and require a high amount of energy. This is because the vital brain chemical dopamine is responsible for communicating messages about movement, among other things. So, what might be going wrong?

Most of us will be familiar with calcium, especially when thinking about diet and its benefits to bone health. But interestingly, calcium has a role completely separate from this. In the brain, calcium can help brain cells communicate and pass on messages.

During high periods of brain cell activity, calcium can start to accumulate. And this build-up of calcium can be harmful to the cell, so one way the cell tries to protect itself is by temporarily storing some of the excess calcium in the mitochondria.

But this can lead to the mitochondria becoming overworked or overloaded with calcium, and when this is the case, an escape valve is forced open. Once this has been opened, mitochondria are unable to function normally and stop producing energy which can lead to cell death. This is thought to be what’s happening in dopamine producing brain cells in Parkinson’s. So, what if we could stop this from happening?

Closing the hole

Knowing that the opening of a valve or hole in the mitochondria is involved in cell death in Parkinson’s makes it an attractive target for the development of potential new drugs to slow, or even stop the progression of the condition. By preventing the opening, or even patching up this hole, it might be possible to preserve the health of these cells. And in turn, ensure a continued supply of dopamine. And that is exactly what NRG Therapeutics Ltd. has set out to do.

What progress has been made so far?

The initial investment into this project allowed Parkinson’s UK and NRG Therapeutics Ltd. to screen a large number of potential drug-like molecules, to see how well they can protect the mitochondria.

The team started with several hundred thousand drug-like molecules and tested their potential by measuring how well they could prevent the mitochondria from malfunctioning. This extensive testing narrowed down and identified some molecules that looked interesting for further study.

Crucially, all these molecules are also able to cross from the bloodstream and into the brain. This means that, further down the line, they could all be made into a drug that could be swallowed as a pill and still be effective, rather than needing surgery to deliver the drug directly to the brain.

Funding for the future

The success of the project led to the Parkinson’s Virtual Biotech investing a further £1.5m funding in this project across 2020 and 2021. The Michael J. Fox Foundation also contributed $500,000 in 2021. These investments have helped to narrow down the most promising molecules that can protect brain cells and get closer to a drug that can be further developed and tested.

Gathering momentum

The growth of the project has made it attractive to other funders too. In May 2022, NRG Therapeutics Ltd. was granted a highly competitive Biomedical Catalyst award of £2.68m, part-funded by the UK government-backed agency Innovate UK. And now in November 2022, it has attracted a further £16m in equity investment, led by American life sciences investment firm Omega Funds and joined by the Australian life sciences venture capital firm Brandon Capital and with further investment from the Parkinson’s Virtual Biotech. This funding will help accelerate the next stage of the project, and hopefully bring the research closer to a place where it would be possible to start conducting clinical trials.

Milestone for the Parkinson’s Virtual Biotech

The extra funding marks a significant milestone for the Parkinson’s Virtual Biotech. Showing how it works. It will invest in research where others won’t, providing the seed funding for the most promising Parkinson’s research. This is now showing results, getting projects to the stage where they are attractive to other investors. We think it’s a bold approach, and one that works.