From a sleep disorder to movement disorder, a new approach to stopping Parkinson’s

When it comes to treating Parkinson’s no treatments have been proven to stop the progressive loss of brain cells that cause the condition. And by the time a person has been diagnosed, there are already signs of damage in the brain. Right now, we have no way of repairing this damage. But researchers believe, if we could spot the condition sooner, it may be possible to start treatments that prevent this damage and slow or even stop the onset of Parkinson’s.

Preventing versus repairing

The idea to find people in the earliest stages of Parkinson’s sounds simple, but has been one of the key challenges for research. This is because the condition affects everyone differently and there is no simple test to either diagnose the condition or accurately monitor its progression. What’s more, some of the earliest symptoms of the condition may not be movement symptoms like tremor, slowness and stiffness.

The movement symptoms of Parkinson’s appear when damage is caused to a part of the brain called the substantia nigra. This brain area, that sits at the top of the spinal cord, contains brain cells that produce the chemical messenger dopamine.

Parkinson’s causes the loss of these cells, in turn reducing the amount of dopamine in the brain. The impact of this is that the brain is missing the key chemical it uses to control movement. Medications like levodopa, aim to replace the dopamine that is no longer being made, but they cannot stop more cells from being lost, so over time more medication is needed to manage movement symptoms.

By the time the movement symptoms of Parkinson’s appear, which often leads to someone being diagnosed, up to half of these dopamine making cells have already been irreversibly lost. Changes in the brain, which for many may have started years earlier, are set in and the opportunity to act early, before the damage has been caused, has passed.

There is research into how to repair this damage, and clinical trials are ongoing that aim to replace the brain cells that have been lost. But what if there were other signs of Parkinson’s that would give us the opportunity to prevent damage rather than repair it?

The earliest symptoms of Parkinson’s

Over the last decade, researchers have been searching for the earliest symptoms of Parkinson’s. Studies like Predict-PD, Tracking Parkinson’s, and those happening at the Oxford Parkinson’s Disease Centre have given vital clues about how Parkinson’s starts.

We now know that, for some, the condition may start in other parts of the brain or even outside the brain and migrate through the body, causing various symptoms that aren’t related to movement. It is only when these changes eventually reach the substantia nigra that the movement symptoms of Parkinson’s appear.

Research has suggested that changes in our sense of smell, sleep or gut may signal the very earliest symptoms of the condition, but it can be hard to know if such symptoms are related to Parkinson’s or some other condition. What we need to know is how many people who experience these symptoms go on to develop Parkinson’s.

Sleep problems and the risk of Parkinson’s

One particular sleep problem has been found to be associated with a particularly high risk of developing Parkinson’s. Recent research suggests more than 70% of adults who experience a type of sleep disorder called Rapid Eye Movement Sleep Behaviour Disorder (RBD), will go on to develop symptoms of Parkinson’s. This sleep condition can cause people to vocalise or act out their often unpleasant dreams, disrupting their and their partner’s sleep.

Understanding sleep problems to prevent Parkinson’s

Brain scans of people who experience RBD show increased inflammation: the body’s natural response to injury, coming from immune cells in the brain called microglia. Research suggests that excessive levels of inflammation in the brain may cause damage to brain cells and play a role in the progression of Parkinson’s.

The involvement of immune cells in Parkinson’s has piqued researchers’ interest in the possibility of dialling down inflammation in the brain. And there is ongoing work through the Parkinson’s Virtual Biotech to find and develop potential anti-inflammatory drugs.

Project Galaxy is focusing on developing molecules that can get into the brain and target a specific protein on the surface of microglia that has been shown to be present at much higher levels in the brains of people with Parkinson’s than in people without the condition. This could pave the way for a future treatment to slow or stop the progression of the condition.

You can read more about Project Galaxy in a recent blog.

Targeting inflammation at the earliest stages of Parkinson’s may also be important when aiming to slow the loss of cells and delay the onset and progression of symptoms. While identifying Parkinson’s early is challenging, doing so opens the door to treating the condition before symptoms become problematic and potentially even preventing people from developing Parkinson’s.

Investing in a Parkinson’s free future

Pharmaxis Ltd, an Australian biotech company, has developed a drug to try and reduce inflammation in RBD. The drug, called PXS-4728, combines an MAO-B inhibitor with an anti-inflammatory agent in a single molecule. This means the drug may have 2 beneficial effects: dampening inflammation and improving Parkinson’s symptoms.

MAO-B inhibitors are already available in Parkinson’s. They boost dopamine levels in the brain by preventing usable dopamine being broken down to improve Parkinson’s symptoms.

The MAO-B inhibitor in PXS-4728 aims to do the same. But more important in this trial is the effect that PXS-4728 has on damaging inflammation in the brain. This anti-inflammatory component aims to slow the loss of brain cells, something no current treatment for Parkinson’s can do.

Now, in a phase 2 clinical trial, which has received £2.9m investment from the Parkinson’s Virtual Biotech, PXS-4728 will be given to people with RBD who are at high risk of developing Parkinson’s.

The trial will take place across 2 research sites, 1 in Australia and 1 in the UK and is due to start in 2023. The trial will aim to recruit 40 participants who will be randomly split into 2 groups: 30 will receive PXS-4728 and 10 will receive a placebo for 12 weeks.

The clinical trial aims to demonstrate that this new treatment is safe and that it has the potential to reduce inflammation in the brain to help slow the progression of Parkinson’s. If so, the next step would be to progress to large-scale trials to further investigate the safety and benefits of this therapy.