Trials to treatments: growth factors

Growth factors are molecules that support the development, growth and survival of our bodies and our brains. Their extraordinary properties make them an exciting prospect for developing new treatments that could help repair the damage caused in Parkinson’s. We take a look at the story so far.

Claire Bale
Jul 10, 2017 · 7 min read

Growth factors are a family of remarkable molecules that play range of important roles in our bodies. These multi-talented molecules play critical roles both in the development of our brains during childhood and in the ability of our brains to change and adapt during adulthood. They ensure that our nervous systems are wired up properly by guiding cells to grow in the right directions and connect correctly with other cells.

The first growth factor

The first growth factor was identified over 60 years ago when an Italian scientist, Rita Levi Montalcini, experimented with transferring pieces of cancerous tumours into chick embryos. She found that it caused nerve cells to start growing like a halo around the tumour cells — it was unlike anything she had ever seen before.

The way the nerve cells were growing suggested to Montalcini that the tumour was releasing a substance that was somehow stimulating the growth of nerves. She then worked with Stanley Cohen to isolate this substance, which they later named Nerve Growth Factor (NGF).

Thirty years later, this work was recognised when Montalcini and Cohen were awarded the 1986 Nobel Prize for physiology and medicine. NGF is now known to be involved in a huge range of vital biological processes, including the regulation of the immune system, the survival of pancreatic cells and even in the biological basis of romance.

Since this discovery, an expanding family of growth factors has been identified. And research has shown that a whole range of these factors seem to be crucial for the growth, development and survival of the brain cells that are affected by Parkinson’s, including:

  • GDNF (glial cell line derived neurotrophic factor) and its close cousin neurturin
  • BDNF (brain derived neurotrophic factor)
  • CDNF (cerebral dopamine neurotrophic factor)
  • MANF (mesencephalic astrocyte derived neurotrophic factor)

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.

The challenges of delivery

Unfortunately it’s not quite as simple as popping these molecules into a pill. They are usually large and complex proteins, which means that getting them to where they need to be, deep inside the brain, is a major challenge.

Different approaches have been tried to overcome this hurdle with varying levels of success:


The first and most direct approach is to insert tubes into the brain and then pump the growth factor straight to the cells that need it. This approach has been tried several times with GDNF in people with Parkinson’s but has produced mixed results. Researchers believe the variation in these results may have been, at least partially, due to differences in the way it was delivered.

The most recent clinical trial of GDNF in Parkinson’s, which finished in early 2017, used a specially designed device involving four separate tubes. These tubes were carefully placed into participants brains using robot-assisted surgery.

Once in place, participants then visited the hospital every four weeks to have GDNF pumped directly through the tubes and into their brains.

Results are coming soon, but encouragingly this approach appears to be safe and acceptable to people with Parkinson’s despite the huge commitment it involves.

Gene therapy

Other studies have tried another route called gene therapy. In this approach, rather than pumping the growth factor directly into the brain through tubes, the idea is to use genetic instructions to encourage brain cells to start making the growth factors themselves.

Scientists have done this by engineering viruses to carry the key genetic instructions required for manufacturing these growth factors. The virus can then sneak into target brain cells and insert the instructions.

The main advantage of this approach is its potential to produce a longer lasting effect. Individuals would have an 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.

This innovative approach has already used by a company called Ceregene. They developed a gene therapy called CERE-120 to insert the genes required for cells to produce neurturin (the close cousin of GDNF). CERE-120 initially showed promise in early stage clinical trials but sadly failed to deliver the hoped for benefit in later studies.

Is there another way?

Both of the above approaches involve complex brain surgery to get growth factors to where they are needed, but could there be another, less invasive, way to boost the levels of growth factors in the brain?

One possible way might be a little unexpected — exercise. Studies have shown that physical exercise triggers an increase in the natural production of BDNF. A recent review suggests that every time we exercise it simulates our bodies to produce a “dose” of BDNF, and that regular exercise helps to increase this “dose” over time. As a result, there are now studies underway exploring whether exercise regimes can help to improve memory and thinking, and how it could be harnessed as a tool to prevent dementia.

Researchers are also investigating if drugs can stimulate the brain to produce more growth factors. One recent attempt was a pill called Cogane that was designed to promote the release of both GDNF and BDNF. Despite showing exciting promise in lab studies, Cogane ultimately failed to deliver the same beneficial effects when it was tested in people with Parkinson’s. Despite this disappointment, there are ongoing efforts to develop these types of therapies.

Current trials

Despite the challenges of delivering them to the right parts of the brain and some setbacks in clinical trials in recent years, growth factors still hold genuinely exciting promise for Parkinson’s — and there are several studies underway currently to keep an eye on.

A gene therapy approach to GDNF

This study is testing a newly developed form of gene therapy that aims to reprogramme brain cells to produce their own GDNF.

The study is taking place in the US and will include 24 patients divided into four groups who will receive different doses of the therapy. The participants will then be followed closely for five years to assess the long-term safety and effectiveness of this experimental treatment. Find out more

The first trial of CDNF for Parkinson’s

In December 2016, the Finnish company Herantis Pharma announced that they had successfully secured funding to carry out the first clinical trial using CDNF in people with Parkinson’s.

The new trial will use the same delivery method that was developed for the recent GDNF trial in the UK. Find out more

A combined therapy to stimulate BDNF

Finally, a research team in New York interested in combining exercise with non-invasive brain stimulation called transcranial magnetic stimulation. Transcranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate particular brain areas.

The American team are carrying out a small trial in people with Parkinson’s to find out whether this combined therapy can boost the natural production of the growth factor BDNF. Find out more

Get connected to the latest research

We’ll be keeping a close eye on these studies and report on any major developments. You can keep up to date with all the latest news on treatments in development by joining our Research Support Network.

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