Dr Eddie Ma Chi-him, Assistant Professor, and his team have developed an innovative form of gene therapy that accelerates the regeneration of injured peripheral nerves, helping patients to recover motor functions during the “critical period”.
Peripheral nerves transmit sensory information collected from around our body to the brain, which in turn issues instructions via the peripheral nerves to our muscles. If a peripheral nerve is damaged, the muscle that it controls weakens, losing mass and motor functions.
The peripheral nerves can regenerate but they grow at only 1mm each day. Thus, if we damage, for instance, the brachial plexus, a network of nerves in our shoulders that conducts signals from the spinal cord to the arm and hand, we might regain only partial arm movement even after a year spent recovering.
Dr Ma and his research team, though, have identified a growth-associated gene, namely “heat shock protein 27” (Hsp27), which enhances the regeneration of peripheral nerves. Their experiments reveal that the Hsp27 expression in mice is normally very low. When they cut the peripheral nerves of the mice and then joined them again through surgery, the mice experienced only a partial recovery of their paws after eight weeks. In addition, muscle atrophy was evident.
In addition, the team found that accelerated axons in mice must reach the muscles within a critical 35-day period; otherwise, it will not be possible to recover motor function, even if the nerves regenerate and reach the contact point of the foot muscle.
This major finding has initiated new research efforts into understanding how to extend, and possibly overcome, the critical period in order to regain 100% motor function.
To further understand the critical period, Dr Ma and his research team observed over 100 patients with Carpal Tunnel Syndrome (commonly known as Mouse Hand, which causes the hands to become numb and lose motor function) and 20 patients with Cubital Tunnel Syndrome (muscle atrophy and numbness) who had received surgery.
They discovered that the nerves of the humans and mice are similar in terms of a specific period of time needed for the best recovery. Patients with Cubital Tunnel Syndrome under observation and receiving surgery had a much higher degree of restored motor function within 10 months of having the symptoms than those having surgery 10 months later.
Dr Ma, who has received $1million in funding from the Early Career Scheme of the Research Grant Council, is currently trying to determine the key molecules that support the growth of regenerating axons during the critical period and also the inhibitory molecules that prevent the joining of peripheral nerves and muscle after the critical period.
Through genetic engineering or small molecular screening, Dr Ma plans to use animal models to test how these molecules affect the regeneration of peripheral nerves during the critical period, how they enhance growth and how they prevent a full recovery of motor function. He hopes that his research can lead to the development of medicine that accelerates the regeneration of nerves.