© Andreas Schaad

The Axon Whisperer

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Fine, we may be exaggerating a little. However, neurologist Zhigang He is one of the first people to succeed in regrowing nerve fibres – i.e. axons – with the help of a specific molecule. We sat down for a chat with the highly respected top scientist

Professor He, anyone interested in neurology and spinal cord research inevitably stumbles upon your name. Was this your childhood dream?
(laughs) No, not really. I studied medicine in China. I first encountered many kinds of patients during an internship and realised that there were no treatments for them. Back then nobody even understood what was behind these clinical problems such as spinal cord injury. It soon became clear to me that I wanted to effect change. That’s why I went into basic research.

What was so exciting about that field?
When you conduct basic research, you soon realise how many questions are still unanswered. Finding new answers is always exciting.

Could you elaborate on your greatest discoveries?
A spinal cord injury disrupts the connection between the brain and the rest of the body. This constitutes a highly complex situation. From the very beginning, the most important question was how to restore the aforementioned connection. One has to realise that evolution took several million years for the body to function so perfectly. We published a paper on PTEN ten years ago. If this protein is eliminated, axons can regenerate.

What exactly is this PTEN?
Cells grow. It’s in their nature. The enzyme PTEN suppresses the constant growth of cells. Eliminating this “growth inhibitor” makes nerve growth possible. But what can be so enormously important for parts of the spinal cord also harbours risks. Eliminating PTEN in glial cells can result in an uncontrolled activation of the cell cycle and thus the forming of tumours. Now we need to work on a safe strategy that has similar effects on nerves as PTEN, but without causing any side effects.

What are you currently working on?
For example, we recently discovered that the molecule osteopontin can render nerve cells more susceptible to the effects of certain growth factors. A combined therapy of molecules and factors has already revealed a successfulregeneration of axons in a cross-sectional model, thus mimicking the effect of PTEN.

What are your next steps in the laboratory?
The laboratory is where we make new discoveries in controlled circumstances. Translating everything we have discovered in the laboratory into clinical applications for patients remains a challenge. We published a paper revealing that we managed to reawaken dormant axons in a mouse last year. These findings have not been widely appreciated yet, but I believe that this approach has a great possibility of helping patients. We are working actively in this direction. 

It seems every answer leads to another question…
Researchers are inquisitive by nature. That is our job.

Zhigang He at the annual Wings for Life Scientific Meeting (Martin Lugger)
Zhigang He at the annual Wings for Life Scientific Meeting  © Martin Lugger

How will spinal cord research change over the next few years?
Spinal cord research has made enormous progress in the last 10 to 15 years. There have been huge leaps in technology and clinical understanding. This development will continue in the coming years. I don’t necessarily believe that complete functional recovery after a spinal cord injury will be possible, but the procedures could resemble those we have for cancer. There will be treatments and not every injury will result in chronic suffering.

Does this mean research will become more clinical in its approach?
Every little piece, every discovery, contributes to the big picture. Based on the data we already have, I am cautiously optimistic. I hope that we will be able to translate many findings into clinical applications.

Do you ever switch off and relax?
I used to ski a lot. Boston is a perfect location for that. I took up snowboarding about seven years ago. It helps me clear my head. I also enjoy playing squash with my daughters. It is great to see they are getting better and better.

What is your vision for the future?
I hope that our research will help patients before I retire. That is my dream.

How much time do we still have?
It won’t take too long, hopefully. The sooner the better…

Zhigang He, who was born in China, is a professor of neurology and Ophthalmology at Harvard Medical School. He directs a research laboratory focusing on neural repair in Boston Children’s Hospital. Zhigang He is married and has two daughters.


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