Parkinson’s patients stop shaking: the important contribution of animal research

Prof. dr. Linden and prof. dr. Temel of the School for Mental Health and Neuroscience

Although they cannot stress the importance of fundamental research enough, that’s not what scientists at the School for Mental Health and Neuroscience (MHeNs) do. “Our non-human research is always aimed at understanding disease models and improving treatment—from Alzheimer’s disease to Parkinson’s, sensory deficits or mental disorders”, says Prof. David Linden, director of MHeNs. One of the most convincing examples of when animal research has led to clinical applications is Deep Brain Stimulation (DBS). Neurosurgeon Prof. Yasin Temel not only applies this technique in patients, but has also performed extensive research on it, and still does. “Without animal research, there would have been no DBS.”

So far, more than two hundred thousand people suffering from Parkinson’s disease have received an implant that helps them stop shaking. The impact on their quality of life is enormous, Prof. Temel knows from real experience. “And it would not have been possible without first testing the effect of DBS on motor, cognitive and emotional behaviour in animals. Testing cognitive skills in rats is not easy, but many aspects of their emotional behaviour are not that different from how humans react.” His own PhD research showed that DBS also affects feelings of depression in rats.

How can you tell if a rat is depressed?
Temel: “Normally, a rat likes drinking sugary water or eating sweets, for example. If it’s depressed, it doesn’t. Or, normally, a rat would swim if you put it in water. A depressed rat doesn’t swim, but drifts. And if you give them Prozac, they will improve.”

Why do you choose to use rats for this type of research?
Temel: “Because it’s the smallest animal species in which we can monitor this type of behaviour. It’s impossible to tell if a fruit fly is depressed. For research on DBS, we need to observe the intact brain and behaviour—a paradigm that also exists in patients—to make the validity of our findings solid. And there’s already so much data from similar animal research to compare results with. If you would stop animal research and leave that all behind, it would take another ten to twenty years to generate this amount of data again.”

Linden: “The alternative models for our field of research are still very limited. There are some cellular models, but they haven’t reached the level of maturity that you would need to draw meaningful conclusions. But the number of animals is being reduced and the number of people benefitting is increasing.”

So how is MHeNs addressing the three Rs of Replacement, Reduction and Refinement?
Linden: “We generally cannot model new treatments entirely in silico or in cellular models, so complete replacement is not possible yet, unfortunately.” Temel: “If a true scientist uses animals, I’m sure he or she has no alternatives. I see them as my patients and I treat them as well as I can. If I see the difference in the number of animals used in an experiment nowadays, compared with fifteen years ago, we have substantially reduced. This is simply because we take a closer look at control groups that are absolutely necessary for a study and because we check if previous results in a similar study can be reused.”

So completely stopping animal research, or outsourcing it to China, is not an option?
Linden: “At the moment, we are legally required to test new drugs in animals, and we need it for the further development of existing treatments and for a better understanding of the early stages of brain development. There won’t be any medical progress or innovation in care in these areas without animal models.”

Temel: “We once considered doing this kind of research in China, but we found out that the ethical standards are quite different there. The number of animals used in a study was enormous, for example. Animal research is ‘a necessary evil’. I’m convinced that good regulation is far better than a complete stop.”

What if the Dutch government indeed bans animal research in the country?
Linden: “The big question then is: will they allow new drugs in the Netherlands if their development has been based on animal models? If they do, one could question the sincerity of the whole approach. If they don’t, they will deny the population access to new important drugs. I don’t see alternative models replacing animal research completely for the next couple of decades. We think it is justified by its medical aims. It also takes place within a very tightly regulated framework (and rightly so) and we have full confidence in our colleagues who do the hands-on work and share our researcher’s agenda: to do the minimum amount of animal research for the maximum effect for patients.”

What is DBS, or neuromodulation?
A deficit in electric currents in our body can lead to brain or nerve cells communicating with each other poorly or not at all. By placing an electrode in a given area of the brain or spinal cord, where our movements are controlled, you can administer additional current and improve the communication between the cells. The result: Parkinson's patients stop shaking and incontinent patients can be rid of their disabling problem. The electrodes are connected via subcutaneous wires connected to a subcutaneous pacemaker with a battery that delivers continuous power. The properties of the current (quantity, frequency, etc.) can be set from outside. That is, quite simply explained, the principle of ‘neuromodulation’.

Fundamental or translational research?
Fundamental research generates new ideas, principles, and theories, which may not be immediately applicable, but form the basis of progress and development in different fields. This type of research rarely helps practitioners directly with their everyday concerns; nevertheless, it stimulates new ways of thinking that have the potential to dramatically improve how they deal with a problem in the future. Translational research builds on fundamental scientific research, for example, to create new therapies and medical treatments.