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Research at the Carl Gustav Carus Institute                                                    

Combining scientific research and therapy on an anthroposophical basis, the need to take up research on the mistletoe plant together with the production of a mistletoe preparation in a new way led in 1967 to the foundation of the Gesellschaft zur Förderung der Krebstherapie e.V. (Society for the Promotion of Cancer Therapy), from which the Carl Gustav Carus Institute (1968), Abnoba GmbH (1971), the Öschelbronn Clinic (1975) and the medical practice (AnthroMed Öschelbronn) (1984) were successively founded. The founding of the institute was accompanied by the development of a new mistletoe preparation, which was later given the name abnobaVISCUM®. Approval, distribution and further development have since been carried out by Abnoba GmbH.

The starting point of all anthroposophical mistletoe preparations are Rudolf Steiner's impulses for an extension of pharmacy [1]. Of particular importance are:

- the harvesting of mistletoe at different times of the year, i.e. the production of two extracts, a summer extract and a winter extract,

- and the mixing of both extracts in order to achieve a new, "more life-like" state of the substance and thus improved efficacy [2].

Thus, when the Institute was founded, 3 fields of work were taken up around mistletoe, one of which related to botany/biology. The second concerned the pharmaceutical-pharmacological research of the total extracts obtained, and the third field of work was the development of a so-called flow process for mixing summer and winter extracts in order to further increase the effectiveness of mistletoe extracts through this process. Exemplary for the studies at the Carl Gustav Carus Institute on the mistletoe plant, its constituents and the cancer disease (see "Publications": current bibliography) are publications by Thomas Göbel on botany/biology and Reinhard Koehler on the flow method.

The white-berried mistletoe is a woody plant and thus related to trees. Therefore, the basis of Thomas Göbel's research on understanding mistletoe was the archetype of the flowering plant and its metamorphosis through the various growth forms up to the trees [3] in its habitat. Such a Goetheanistic approach - to look at and understand the individual from the inherent natural principle of the whole - is still present at the Institute today. The spectrum of research topics was supplemented by Heinrich Brettschneider with the anthroposophical study of man [4] and Rolf Dorka with chronobiological research [5].

Fig. 1: Mistletoe shoot development over 3 years.

Exemplary for this Goethean research are rows of leaves from the buttercup family, which can be made available to interested experts for research purposes. More details can be found here. For the study of leaf metamorphoses, the buttercups are particularly well suited due to their great diversity. In comparison, it clearly shows how reduced Viscum album L., the white-berried mistletoe, is in the formation of its leaves. Mainly the European genera of the buttercups were one of the fields of research in the biological department of the Carus Institute for many years.

Reinhard Koehler used experimental and natural flow processer (as they occur in rivers, in the oceans, in the weather, in humans) to develop the extent to which these flow processes serve to build up and break down in the living. His concept envisaged mistletoe extraction "close to the living" and a flow machine that keeps the extracts open to changes caused by flow processes. Together with Michael Feles and Armin Scheffler, he succeeded in producing a green, colloidal (liposomal) mistletoe extract (fig. 2) "close to the living" using a novel method (at the time) [6 - 8].

Fig. 2: The result is not a clearly transparent extract, but an opalescent one, which shows the so-called Tyndall effect, made visible by a beam of light incident from the side, which causes a luminous cylinder to appear in the liquid. This effect is based on scattered light, caused by colloidally dissolved vesicles, also called liposomes, contained in the extract, which form spontaneously through self-organisation from the cell and organelle membranes released during extraction.

From the very beginning, the colloid as a symbol of the "living" was the focus of research at the Carl Gustav Carus Institute and the development of the flow machine. Through flow processes, a membrane synthesis of these colloid particles (liposomes) should be brought about in the sense of Steiner's impulse mentioned above. Their proof was provided in 2011 by the work of Vrânceanu [9]. You can find a summary report on "Anthroposophical drug developments in Öschelbronn" in the "Akzente" 2016/17 on pages 20-27 (in German).

On the basis of these founding impulses, research is currently taking place at the Carl Gustav Carus Institute under the leadership of Gero Leneweit with the aim of developing a new, targeted mistletoe preparation, in which tumour-effective substances/extracts of mistletoe are encapsulated in biological lipid membranes, the liposomes (Fig. 3), and brought to the tumour [10-13].

Fig. 3: Liposomal formulations are the subject of our research. Liposomes are spherical membrane vesicles that protect the mistletoe ingredients from the degrading effects of the immune system. By embedding the mistletoe extract in natural biological membranes, liposomes are created in the injection preparation.

Fortunately, we have made great progress in this development through a previous EU cooperation [11] by developing a water-in-oil nanoemulsion centrifugation process. This process enables the encapsulation of mistletoe substance. Together with researchers from the University of Angers in western France and the company GlioCure SAS, which emerged from it, we will be working on novel therapies for brain tumours in the next few years. This is funded by the European Union as well as by national funding from Germany, France, the Netherlands and Sweden within the framework of the "Eurostars" funding programme.

You can also read the interview on "Current research results at the Carl Gustav Carus Institute" conducted by Britta Bischoff-Krappel (freelancer Pforzheimer Zeitung) with Dr Gero Leneweit (Institute Director) on 18 May 2019. You can access the interview here.

Literature

1. Steiner R. Physiologisch-Therapeutisches auf Grundlage der Geisteswissenschaft. Zur Therapie und Hygiene. GA 314. 3. Vortrag vom 27.10.1922. 4. Aufl. Dornach: Rudolf Steiner Verlag; 2011.

2. von Laue HB. Die Entwicklungen des pharmazeutischen Impulses bei Rudolf Steiner. Menschenkundliche Voraussetzungen einer anthroposophischen Pharmakokinetik. Der Merkurstab 2008;61(1):4–47. DOI: https://doi.org/10.14271/DMS-19199-DE.

3. Göbel T. Zur Raum- und Zeitgestalt der Weißbeerigen Mistel, Viscum album L. In: Scheer R, Becker H, Berg PA (Hg). Grundlagen der Misteltherapie. Aktueller Stand der Forschung und klinische Anwendung. Stuttgart: Hippokrates Verlag; 1996: 3–27. Das pdf dieser Arbeit kann hier heruntergeladen werden. The pdf of this (German) article can be downloaded here.

4. Brettschneider, H. Anthroposophische Medizin - Heilmittelerkenntnis und Menschenbild. Komplementäre und integrative Medizin (KIM), Ärztezeitschrift für Naturheilverfahren 2009; 01-02: 37-45 (Teil 1), 03: 15-18 (Teil 2), 04: 56-59 (Teil 3). Elsevier Verlag, Amsterdam.

5. Dorka R, Engelmann W., Hellrung W. Chronobiologische Untersuchungen an Viscum album L und ihre pharmazeutische Relevanz. In: Scheer R, Bauer R, Becker H, Fintelmann V, Kemper FH, Schilcher H (Hg). Fortschritte in der Misteltherapie, aktueller Stand der Forschung und klinische Anwendung. KVC-Verlag, Essen; 2005: 23-34.

6. Feles M, Koehler R, Scheffler A. Abnoba GmbH, assignee: Verfahren und Vorrichtung zur Herstellung von Presssaft aus Pflanzen. Europäisches Patent Nr. 0288603; 1991.

7. Scheffler A. Heilpflanzenerkenntnis aus Sicht der anthroposophischen Medizin am Bespiel der Mistel Viscum album L. In Scheer R., Bauer R., Becker H., Berg PA., Fintelmann V. (Hg.): Die Mistel in der Tumortherapie – Grundlagenforschung und Klinik, KVC Verlag, Essen; 2001: 519-558.

8. Scheffler A. Neue Aspekte zur Herstellung von Mistelpräparaten. Therapeutikon 1990; 4: 16 – 22.

9. Vrânceanu M, Terinte N, Nirschl H, Leneweit G. Asymmetric or symmetric bilayer formation during oblique drop impact depends on rheological properties of saturated and unsaturated lipid monolayers. Journal of Colloid and Interface Science. 2012; 354: 45-54.

10. Beztsinna, N, de Matos MBC, Walther J, et al. Quantitative analysis of receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 by high content imaging. Nature Scientific Reports. 2018; 8, 2768, 1-10. pdf kann hier heruntergeladen; pdf can be downloaded here.

11. De Matos MBC, Beztsinna N, Heyder C, et al. Thermosensitive liposomes for triggered release of cytotoxic proteins. European Journal of Pharmaceutics and Biopharmaceutics. 2018; 132: 211-221. Link zu diesem Artikel; link to this article: https://www.sciencedirect.com/science/article/pii/S0939641118305915

12. De Matos MBC, Miranda BS, Nuari RY, et al. Liposomes with asymmetric bilayers produced from inverse emulsions for nucleic acid delivery. Journal of Drug Targeting. 2019; 27: 681-698. Link zu diesem Artikel; link to this article:https://doi.org/10.1080/1061186X.2019.1579819 

13. Ullmann K., Meier M., Benner C., Leneweit G., Nirschl H.  Water-in-Fluorocarbon Nanoemulsions Stabilized by Phospholipids and Characterized for Pharmaceutical Applications. Adv. Mater. Interfaces. 2020; 2001376. DOI: 10.1002/admi.202001376. Die Veröffentlichung steht hier zum Download zur Verfügung; pdf can be downloaded here.


Carl Gustav Carus-Institut der Gesellschaft zur Förderung der Krebstherapie e. V. | Allmendstr. 55 - 75223 Niefern-Öschelbronn | Tel.: 07233 7043-100 | www.carus-institut.de