Source: Revalidatie Magazine – Januari 2016
Translation from Dutch to English by our volunteer Beverley Saunders.
“We’re trying to shake the nerve cells awake”
By John Ekkelboom
In addition to the development of technological aids for people with spinal cord injuries, scientists worldwide are involved in researching a possible cure for this condition. Joost Verhaagen, Professor in the Molecular Biology of Nerve Tissue Regeneration at the Vrije Universiteit Amsterdam (The Netherlands) is amongst these tenacious researchers. He emphasizes that his research is fundamental and that the road to the clinic will take many years. If proven successful, his Gene Therapeutic approach will likely include a combination of two angles.
“The spinal cord regenerates poorly after a spinal cord injury,” Verhaagen explains. “This is because all the scar tissue inhibits growth of new nerve fibers. Moreover, nerve cells in the central nervous system do not have the capacity to activate the gene program to stimulate nerve re-growth. On both fronts, we want to encourage the body to start the regeneration process. To this means, we receive financial support from ZonMw and we work closely with endParalysis – an enthusiastic international patient organization led by Corinne Jeanmaire, who is totally committed to accelerating research for a cure for spinal cord injury.
One of the weapons used by the Professor is ENZYM CHONDROITINASE. This breaks down the scar tissue. His research is carried out in collaboration with King’s College in London (UK). “In rats with spinal cord injuries a virus, (Cripple virus) constructed with the DNA of this enzyme, was injected into the injured area where it entered the affected cells. In this way the Chondroitinase Enzyme is expressed and scar tissue is partially eliminated. But we must also be able to stop this expression when the job is done. After all, the skeleton of the scar tissue that remains is required for the outgrowth of nerve cells. Furthermore, Chondroitinase is a foreign protein body and possible immune reactions in the future must be avoided. We are now examining the possibility of regulating the expression of the enzyme with the antibiotic Doxycycline.”
Removal of the scar tissue is not enough: it only paves the way for the desired growth of nerve cells. The next step is the awakening of these nerve cells. Verhaagen has studied the genes which react when the peripheral nervous system is damaged. Certainly, sensory and motor neurons are well able to recover spontaneously. The professor traced 1500 genes that are possibly involved and selected nine key genes. “Using different combinations, these genes will be expressed via a viral vector into the damaged nerve cells of the spinal cord. The hope is that they eventually grow and make new connections with neighboring neurons. ”
The research into removal of scar tissue is the most advanced. Verhaagen anticipates, that in a few years, there will be more clarity as to whether this approach may be applied to patients. Gene Therapy for dormant nerve cells is still at an early stage. The neuro-scientist does definitely not want to raise false hopes and he is particularly disturbed by the scientific hypes that are presented to spinal cord injury patients from time to time. Should his combined therapy finally work then rehabilitation will, according to him, once again play an important role in the recovery process. “At present, as well as the other benefits, the rehabilitation of patients suffering from spinal cord injury ensures beter functioning of undamaged nerve cells. Ultimate success of our plan will require supplement rehabilitation to create a beneficial effect on the regenerating nerve cells. The biological approach then receives an extra boost to achieve success. ”
(Text with photo)
Joost Verhaagen (Delft, 1956) studied biology at Utrecht University. As a postdoc he worked at an American subsidiary of the pharmaceutical company Hoffmann-La Roche. He then served as a research neuro-scientist at the Rudolf Magnus Institute in Utrecht. Presently, he works at the Dutch Institute for Brain Research and is endowed Professor in the Molecular Biology of Nerve Tissue Regeneration at the Vrije Universiteit in Amsterdam. In addition to his work, walking is one of his hobbies.
spinal cord injury research