Damage to the spinal cord rarely heals because the injured nerve cells fail to regenerate. The regrowth of their long nerve fibers is hindered by scar tissue and molecular processes inside the nerves. An international team of researchers led by DZNE scientists in Bonn now reports in Science that help might be on the way from an unexpected quarter: in animal studies, the cancer drug epothilone reduced the formation of scar tissue in injuries to the spinal cord and stimulated growth in damaged nerve cells. Both promoted neuronal regeneration and improved the animals' motor skills. (suwe)
Nerve cells are wire-like conductors that transmit and receive signals in the form of electrical impulses. This function can be impaired by accidents or disease. Whether or not the affected nerves can recover largely depends on their location: for instance nerve cells in the limbs, torso and nose can regenerate to some degree and regain some or all of their function.
Cross section rat spinal cord. Immunostaining: axons (red), synapses (green), motor neurons (blue)
Source: DZNE/Jörg Ruschel
In contrast, the neurons in the brain and spinal cord do not have this ability. If they are damaged by accident or disease, the patient is likely to suffer long-term paralysis or other disabilities. But why is regeneration of these neurons and their long nerve fibers impeded? It is already known that inhibiting factors in newly formed scar tissue and other cellular processes block axon regrowth.
Seeking the ideal treatment
"The ideal treatment for promoting axon regeneration after spinal cord injury would inhibit the formation of scar tissue," says Professor Frank Bradke, who leads a working group at the DZNE's site in Bonn and who conducted the study. "However, it is also important that the growth-inhibiting factors are neutralized while reactivating the poor axons' regenerative potential." A feasible administration of a potential treatment is also essential for clinical application.
In cooperation with international researchers, Bradke and his team have now managed to take another step towards the development of a future treatment. From their previous research, it was already known that stabilizing microtubules would reduce the formation of scar tissue and promote axonal growth. Microtubules are long, tubular filaments inside the cell that can grow and shrink dynamically. They are part of the cell's supportive skeleton, which also controls cell growth and movement.
The substance epothilone can stabilize microtubules and is already licensed on the American market - as a cancer treatment. "It all depends on the dose," says Dr. Jörg Ruschel, the study's lead author. "In higher doses, epothilone inhibits the growth of cancer cells, while low doses have been shown to stimulate axonal growth in animals without the severe side-effects of cancer treatment." Epothilone is superior to other cancer drugs with a similar effect because it can penetrate the blood-brain barrier into the central nervous system, thus reaching the damaged axons directly.
One substance - many effects
Experiments have shown epothilone works on several levels. Epothilone reduces the growth of scar tissue by inhibiting the formation of microtubules in the cells that form the scar tissue. Therefore they cannot migrate to the spinal cord lesion and cause wound scarring. At the same time, epothilone promotes growth and regeneration in the nerve cells by causing microtubules to grow into the damaged axon tips.
In short: through the same effect, namely microtubule stabilization, epothilone is able to inhibit directional movement in scar-forming cells while stimulating active growth in nerve cell axons. The animals treated with epothilone after spinal cord injury walked better than those that received no treatment, due to improved balance and coordination. The next goal of Bradke and his team is to test the effect of epothilone on various types of lesion.
„Systemic administration of epothilone B promotes axon regeneration after spinal cord injury”, Jörg Ruschel, Farida Hellal, Kevin C. Flynn, Sebastian Dupraz, David A. Elliott, Andrea Tedeschi, Margaret Bates, Christopher Sliwinski, Gary Brook, Kristina Dobrint, Michael Peitz, Oliver Brüstle, Michael D. Norenberg, Armin Blesch, Norbert Weidner, Mary Bartlett Bunge, John L. Bixby and Frank Bradke, Science, 2015, doi: 10.1126/science.aaa2958
The German Center for Neurodegenerative Diseases (DZNE) investigates the causes of diseases of the nervous system and develops strategies for prevention, treatment and care. It is an institution of the Helmholtz Association of German Research Centres with sites in Berlin, Bonn, Dresden, Göttingen, Magdeburg, Munich, Rostock/Greifswald, Tübingen and Witten. The DZNE cooperates closely with universities, their clinics and other research facilities. www.dzne.de, www.twitter.com/dzne_en.
Public and Political Affairs
Tel.: ++49 228 43302 263
Further materials (pictures and videos) are available upon request.
Ulrike Koch | idw - Informationsdienst Wissenschaft
Hunting pathogens at full force
22.03.2017 | Helmholtz-Zentrum für Infektionsforschung
A 155 carat diamond with 92 mm diameter
22.03.2017 | Universität Augsburg
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
22.03.2017 | Materials Sciences
22.03.2017 | Physics and Astronomy
22.03.2017 | Materials Sciences