Dietmar Fischer: A far-reaching coincidence
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- Dietmar Fischer is a Junior Professor at the University Clinic, Ulm. Quelle: Universität Ulm
25.07.2007 -
In the beginning, coincidence led the way when the doctorand Dietmar Fischer discovered something quite unbelievable, i.e. that injured nerve cells can regenerate themselves if the lens in the eye has been damaged some time beforehand. This was seven years ago. Since then, Fischer, now Junior Professor at the University Clinic, Ulm, has dedicated his working life to uncovering the mechanism that forms the basis of this process. If this can be achieved, the pharmacist hopes to use the knowledge to develop treatments for various conditions. The animal model has produced many promising results, and in the process, the 35-year-old researcher even managed to discover a new gene.
The enthusiasm for Fischer's area of research came in large part from his doctoral advisor, as did the idea of working in areas where therapies have yet to be developed, such as spinal cord injuries or other injuries of the central nervous system (CNS). "My greatest motivation was, and still is, to contribute at some point to the development of therapies that can help patients", says Fischer. At the outset, he wanted to know why neurotrophic factors weaken the decay process of damaged nerve cells in the retina (retinal ganglion cells) if they are applied to the vitreous body of the eye. Today, Fischer knows that this approach wouldn't have taken him very far.
A coincidental find and secret experiments
At that time, a stroke of luck in the laboratory came to the aid of the then postgraduate student: "I inadvertently damaged the lens with the injection. It was perhaps lucky that I had relative little experience in the field and was fairly happy-go-lucky. I had recognised in various assays (in those used for measuring regeneration) that I had thereby induced a strong regeneration. At first I did not know why this was, but I did some more experiments in order to find out. When I showed my doctoral advisor the data, he was very excited."
Fischer had found his area of research. Since that time, he has not abandoned the question of what exactly caused this regeneration. His publication from the year 2000 made a sizeable impact. Previously, no other treatment had succeeded so strongly in protecting nerve cells and returning them to a state of active regeneration, so that the fibre-like axons were able to form again.
From Boston to Ulm for patriotic reasons
As coincidence would have it, a group from the Harvard Medical School published a paper with the same results at the same time as Fischer, who then joined the group before working for them from 2001 to 2004, which was followed by his Junior Professorship at Ulm University in 2004 in the Neurology department.
Fischer does not regret returning to Germany, despite the outstanding research conditions at Harvard Medical School. Indeed, this scientist, lavished with German taxpayer-provided public funding, regards it as his patriotic duty to repay his mother country with the support that his research provides.
With the help of an elaborate microarray study, Fischer hoped to clarify exactly which genes were switched on and off in the regenerated cells in the process of his coincidental discovery. With this, the researcher became a discoverer of genes. Fischer filtered 94 genes out of the total of 16,000 surveyed genes. Among them were also some that had never before been characterised.
Daughter provides naming inspiration
Identifying and characterising these genes is one of the major goals for Fischer's laboratory. One of these genes has been called LINA, the name of his daughter, because it was discovered and cloned on her first birthday. LINA stands for "Lens Injury Induced Factor with Neurite Outgrowth Promoting Activity" and seems to be particularly important for the regeneration of damaged nerve fibres. This has been proven by gene-therapeutic attempts using rats, accomplished in Fischer's own laboratory. Humans also carry the LINA gene, which is very similar to the rat version.
In the meantime, Fischer has discovered secondary processes that take place after the lens injury. These are possibly suitable as a therapy approach to imitate the regeneration effects of the lens injury. The technique has already succeeded with rats.
Despite “promising” results in the animal model (rat), the question is put to Fischer as to whether these can be transferred to humans. The scientist answers first with a careful "perhaps", which eventually becomes a "probably", before he finally ends all speculation with the words: "We don’t know. All researchers should say that, before studies on humans have been accomplished."
Fischer knows that his realisations could well have extensive (therapeutic) consequences. This is because, according to Fischer’s statements, the eye can be understood as a model. The mechanisms that take place in the eye can in principle also be transferred to other injuries of the CNS: Parkinson’s, brain injuries or strokes. However, the exact mechanism of the effect must be better understood. Fischer is confident: "We are on a good path".
One therapy alone doesn’t lead to a result
Nerve cells are normally unable to regenerate because of the inhibiting factors in the myelin and because of the scar that develops after the injury has healed. Receptors are necessary for recognising these inhibitors. In their ability to interfere in the process, Fischer has succeeded in developing a gene-therapeutic approach: In such a way, the nerve cells grew into the myelin and overcame the scar.
According to Fischer, however, it is not enough to switch off these signal pathways. Beforehand, the nerve cells have to be stimulated into axonal growth. Only this combination can lead to "therapeutically relevant regeneration". Now, this realisation is becoming more widely accepted and Fischer feels that his techniques have been confirmed.
A number of strategies to lead to therapies
Together with his seven-strong team, Fischer is pursuing a number of strategies that could lead to possible therapies. The effect mechanism of a lens injury must be characterised for further analysis, LINA biochemically tested and before being tested on the spinal cord with other groups of researchers. It is very possible that Fischer will discover yet more genes that play an important role in the regeneration of nerve cells.
Even if Fischer is not classical basic researcher and, as a pharmacist, is always looking for an application from the animal model - the regeneration of nerve cells project is still not close to reaching its goals. Progress could possibly be accelerated if the researchers go further backwards in the eye, beyond the chiasm, where the optic nerves meet the base of the brain. In the meantime, and from his own experience, Fischer knows very well that "much is a result of coincidence - good discoveries are usually coincidental discoveries."
Source: Text first published in German at www.bio-pro.de
