GDNF and other growth factors

What are growth factors and what trials are underway to explore their potential to stop, slow or reverse Parkinson’s?

Growth factors are proteins that our bodies produce naturally to support the development, growth and survival of our bodies and our brains. They play a critical role in how cells develop and grow throughout our lives. In our brains, they ensure that cells are wired up properly by guiding them to grow in the right directions and connect correctly with other cells. They also help to keep cells healthy and to protect them from damage.

In Parkinson’s, brain cells that produce a vital brain chemical called dopamine become damaged, stop working properly and eventually die. As these precious cells are lost, the brain struggles to make enough dopamine to carry out specific functions properly. This results in symptoms such as difficulty starting and controlling movement, as well as non-movement issues like sleep problems and low mood.

But could boosting the levels of growth factors that nurture and support dopamine producing brain cells help to protect or even repair the damage caused in Parkinson’s?

Growth factors are often described as fertilisers for the brain because of their abilities to nourish and revive brain cells, and to stimulate new growth. These properties have made them a target for the development of new treatments for Parkinson’s. If we can boost the levels of some of these key molecules in the brain areas that are affected in the condition, perhaps they could prevent further damage or loss of cells, or even help struggling cells to regrow.

Turning growth factors into treatments

Through decades of research scientists have discovered a number of different growth factors that may have potential for supporting the brain cells lost in Parkinson’s. Several are now being tested in clinical trials, so let’s take a look at these promising new treatments in more detail.

GDNF (glial cell line derived neurotrophic factor) 

GDNF was first discovered in 1993 and is the most studied growth factor in Parkinson’s.

Early lab studies showed that GDNF has powerful effects on dopamine-producing cells grown in a dish. It can help dopamine cells survive and regenerate, and further experiments suggested GDNF can rescue the brain cells lost in Parkinson’s in animals.

These promising findings quickly led to clinical trials.

Unfortunately, because GDNF (like all growth factors) is a large protein, it cannot simply be put in a pill as it would never reach the brain. So initial trials involved surgery to implant tubes into the brain to allow GDNF to be pumped directly to the brain cells affected.

There have now been several studies using this approach. The most recent trial, funded by Parkinson’s UK, published results in 2019. There were promising signs in brain scans that GDNF was reawakening dying brain cells, but the effect on symptoms was not clear cut.

And while the surgery and device that was used to deliver GDNF was shown to be safe, the surgery coupled with frequent visits to have the drug pumped into the brain, make this a complex and difficult approach. 

Find out more about the most recent study of surgically delivered infusions of GDNF, published in 2019

More recently, a new approach to delivering GDNF has been developed called gene therapy.

In this approach, the idea is to use genetic instructions to help brain cells to start making more of the growth factors themselves.

Scientists have done this by engineering harmless viruses that act as a delivery package to carry the key genetic instructions required for producing these growth factors. The virus can then sneak into targeted brain cells and insert the instructions to increase the production of the specific growth factor in the location where it might have a significant impact.

The main advantage of this approach is its potential to produce a longer lasting effect. Individuals would have a single operation to have the gene therapy carefully injected into the right brain areas, but then their brain cells should start producing growth factors naturally without the need for repeat doses.

Early stage clinical trials using gene therapy to deliver GDNF are now underway. Initial results in small studies involving people with Parkinson’s suggest that this pioneering approach is safe and that it successfully helps brain cells to start making more of their own GDNF.

Read more about AB-1005 one gene therapy that has reported initial results on the AskBio website.

Further international studies are now on the way to look at this gene therapy in a larger group of people with Parkinson’s and to explore whether it can actually slow, stop or reverse the condition.

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CDNF (cerebral dopamine neurotrophic factor)

CDNF is one of the newest growth factors on the block and was only discovered in 2007.

In lab experiments, CDNF can restore dopamine-producing brain cells. And studies in animals suggest that CDNF has the potential to improve both movement symptoms, and other symptoms like anxiety that affect many people with the condition.

A first trial of CDNF has been carried out in people with Parkinson’s using surgically implanted tubes to deliver the protein to the brain, similar to previous GDNF trials. This initial study suggests that CDNF therapy is safe and potentially encouraging but there is a move to find a less invasive way to take this research forwards.

Read the full scientific paper of the CDNF in the journal of Movement Disorders.

Herantis Pharma, the company developing CDNF as a therapy for Parkinson’s, is now exploring alternative (and less invasive) ways to achieve its effects inside the brain.  

They have developed a drug called HER-096 based on a small but important fragment of the CDNF protein. Lab experiments show that HER-096 has similar effects to CDNF, but, unlike the large CDNF protein, it can pass from the bloodstream into the brain. This means it can be given by a simple injection.

In October 2023, Herantis announced positive results from a first clinical trial in healthy volunteers. The company is now partnering with the us, through the Parkinson's Virtual Biotech, and The Michael J. Fox Foundation for Parkinson’s Research (MJFF) planning a first clinical trial in people living with Parkinson’s to see whether this new CDNF-inspired drug is safe and potentially effective for those with the condition.

Read more about the announcemnt to fund the CDNF trial on our news pages

BDNF (brain derived neurotrophic factor)

BDNF was discovered in the early 1980s and alongside supporting the growth and survival of brain cells it also plays an important role in neuroplasticity.

The term neuroplasticity describes the brain's remarkable ability to form and strengthen new connections throughout our lives. These changes in how brain cells connect and speak to each other enable us to learn new things and form memories. They also enable our brains to adapt to changes, for instance rewiring itself in response to injury or damage.

So BDNF is a really important growth factor in neurodegenerative conditions like Parkinson’s and Alzheimer’s where brain cells are dying, not only in helping to protect these precious cells, but also in helping remaining cells to adapt and compensate for those that have been lost.

Studies suggest that people with Parkinson’s have lower levels of BDNF than people without. And that lower levels of BDNF may be linked to depression, and memory and thinking problems in those with the condition.

So, low BDNF levels may be contributing to the development of Parkinson’s, and finding ways to boost BDNF could help to protect vulnerable brain cells and improve mood, memory and thinking.

One possible way might be a little unexpected – exercise. Studies have shown that physical exercise triggers an increase in the natural production of BDNF in the brain.

Lab studies have shown that exercise can stimulate protective and restorative effects in animals treated to develop similar changes in the brain to Parkinson’s. These studies also suggest that these beneficial effects may be, in part, due to increased levels of BDNF.

Meanwhile, researchers have found that regularly participating in aerobic activity (something that gets your heart rate up, like brisk walking or swimming) caused changes in brain structure and function in people with Parkinson’s when they looked at scans of their brains.

Read more about the research results that looked at brain changes in response to physical activity in Parkinson’s.

We’re still learning about the benefits of exercise, and its potential for protecting our brains. But it’s likely that we can all do something to boost our growth factors to give our brains a helping hand. 

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