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Serge Bischoff - Research description

Serge Bischoff - Research description

Dr.Serge Bischoff has accumulated 38 years of experience in the field of neuroscience research, including 28 years in the research departments of major pharmaceutical groups. He began his professional career as a senior technician in 1969 in the Research Unit of Neurobiology of INSERM U.109 Professor Jean-Charles Schwartz, in Paris. At the same time continuing her education in evening classes at the Faculty of Sciences, Paris VI University, Dr. Bischoff received his Ph.D. in 1975 under the direction of Prof.. J.-C. Schwartz, B. Droz (Chairman) and P. Ascher. In 1976, he obtained his first research position in the pharmaceutical industry Synthélabo, in Bagneux (now Sanofi Aventis and Sanofi recently). Under the direction of Prof. J. Korf, and in collaboration with Dr. B. Scatton (Vice-Chairman of the group), he explores the biochemistry of the neurotransmitter dopamine and discovers a new path neurons: dopaminergic innervation of the mesencephalon in the hippocampus. Recent studies by the Nobel Laureates Dr. E. Kandel and P. Greengard input indicate that the hippocampus modulates the formation of memory, and could be directly linked to cognitive deficits in schizophrenic patients.

With this discovery, S. Bischoff was hired in 1979 by the major group Basle CIBA-GEIGY (Switzerland) with the mission to develop a new research program of antipsychotic drugs selectively acting on the dopaminergic system meso - hippocampal. In two years, he obtained his first responsible position: he became head of research programs in schizophrenia and depression. It contributes to R & D effort of the company and led several molecules in the clinical development phase, two antipsychotics, selective antagonists of dopamine receptors in the hippocampus (Savoxepine and CGP 27722) and a positive modulator of these receptors, developed as antidepressants (CGP 25454).

The concept of positive modulator of dopamine receptors by dual action on the receptors pre-and postsynaptic initiated by S. Bischoff later became known by another Nobel laureate, Prof.. Arvid Carlsson, who developed under the name of stabilizing dopaminegique.
To refine and expand its areas of expertise, Dr. Bischoff gets a post of visiting scientist at the prestigious Salk Institute in La Jolla, California (1993-94). He deepened his knowledge of the glutamate system in the brain and forms in the field of neuroanatomy. Back at CIBA-GEIGY, he is called to launch a new program to search for drugs in the field of AMPA receptors and kainate glutamate for application in stroke (cerebral embolism) and epilepsy. This collaborative project brought together some thirty researchers and technicians, continued after the merger of Ciba-Geigy and Sandoz in NOVARTIS, led to the discovery of the first antiepileptic drug benefit to patients previously resistant to treatment. This candidate drug (AMP397) is still developing and has generated an intensive search for successors.

After this success, S. Bischoff is to create a program in the field of estrogen with the mission to discover antagonists to beta receptors as new antipsychotics. In parallel, it is responsible for setting up and directing a broad collaborative program with the MPRC, Maryland Psychiatric Research Center, Baltimore ($ 12 million over 6 years, 1997-2003). The aim is to translate basic knowledge of neuroscience research and clinical drug discovery programs. One approach has major consistée in search of new therapeutic targets in schizophrenia by conducting comparative studies of genome and proteome of the brains of schizophrenic with brain controls. Finally, during the same period, Dr. Bischoff was a major part in the cloning of GABA B receptors and the discovery of subtypes GABA BR1 and GABA BR2. In 2001, Dr. Bischoff took responsibility for a period of year of the partnership between the prestigious Institute of La Jolla, the Scripps Research Institute (TSRI) and Novartis, which is the main funder. The mission was to identify and support the work of the TSRI research may offer new therapeutic targets (and pathways) and to generate new research programs in all areas of therapeutic NOVARTIS.

At the end of this year, and after a brief return to Basel, S. Bischoff decides to end his career with Novartis to being available for new adventures science (August 2003) and managerial.

To summarize this phase of life, S. Bischoff conducted simultaneously a research career in the field of neuroscience that led to several discoveries compiled in 77 articles published in major international scientific journals, and research applied to drug discovery. He acquired both the international scientific recognition awarded the Young Scientist Award of the Swiss Society of Biological Psychiatry (in 1988) and Novartis in a solid expertise in R & D and especially in Drug Discovery. With a vision at all times to patients, S. Bischoff played a key role at the interface of basic science, research pharmaceutical preclinical and clinical studies. He held numerous management positions in the highly competitive search for new drugs as head of research programs in a giant global pharmaceutical companies, covering a broad spectrum of therapeutic applications (schizophrenia, depression, stroke , epilepsy). With its ability to carry out these projects and activities very different and its presence in the pharmaceutical world, he was awarded the distinction of Leading Scientist by the Executive Committee of Novartis (1999). Since 2002, S. Bischoff began a new adventure, that of entrepreneurship. It lays the foundation for a biotech start up with the prof. M. Baudry and G. Chauvet. Initially, its role, as a pharmaceutical team is evaluating the possibility to apply to pharmaceutical research the theory of integrative physiology built by G. Chauvet since the 80s. This idea is in S. Bischoff echoed quite favorable because it provides an answer to a question for decades led by many researchers in the pharmaceutical industry: how can we find drugs on the basis of their action on physiological functions in a whole? If the idea is not new, what has been missing are both the technological tool for taking into account the complexity and kinetic data for 'set' the dynamic biological processes. After a construction phase of an embryonic technology platform simulation of memory, the team joins Dr. Y. Al Kazzaz to create the company in March 2004 Lifelike Biomatic, registered in Delaware, USA. S. Bischoff led the Drug Discovery Program and enjoy the company of his experience of group dynamics and project management pharma. But its network of knowledge and its implementation are in France, especially in Alsace, where he lived most of his life. From December 2004, alongside the work of building a platform and its first experimental validation, S. Bischoff began to seriously consider the possibility of establishing a subsidiary of LLB in Alsace. He began to build its network of knowledge, supported by a growing number of economic development agencies in Alsace, Basel and the Pays de Bade (ADIRA, ADA, Regional Council, CCI Mulhouse Sud Alsace and CEEI, and BioValley Pôle d'Innovation Thérapeutique, Technopole de Mulhouse, CAHR, CAMS, Rhenaphotonics training), established first contacts with biotechs and start up of the region (Faust, Forenap, NOVALYST, Alix, System Vip's), with major groups the pharmaceutical (Novartis, Roche) and with researchers and / or representatives of universities ULP, UHA, Freiburg, Basel and Bern. Contacts are also made with groups of investors, but with them is quite quickly a major obstacle: the inability to grow as a subsidiary of a U.S. company. In June 2006, and after more than a year of stagnant U.S. LLB, S. Bischoff and M. Baudry decide to create a research bio - pharmaceutical independent LLB Europe renamed Rhenovia Pharma. Quickly joined by Michel Faupel, former co-founder of BioValley, and deeply rooted in the economic fabric sorting - the national team is in place the infrastructure, strategies for development of business. S. Bischoff is first co-opted by the CEEI Alsace, received the Entrepreneur of the passport CCI Mulhouse Sud Alsace is accepted to the incubator Technopole de Mulhouse Rhenovia or its headquarters in September and receive approval Commitment Committee that recognizes its innovative enterprise to enter the semi Incubator.
Rhenovia Pharma SAS is formally established on 3 May 2007. S. Bischoff took the duties of CEO. That year Rhenovia win or finalist in several regional, national and international, in particular, Rhenovia has won the 2007 national competition for the creation of innovative technology company to the Ministry of Higher Education and Research.
In August 2008, Rhenovia has a team of 20 persons including 6 employees covering all the skills required to successfully complete the project and is preparing its first partnership project / service with a giant in the pharmaceutical industry. Rhenovia has passed a first fund of 1 million.

A full list of 80 publications in international journals is available on request. Below is the 33 most significant publications.

1. Schwartz JC, Lampart C, Rose C, Rehault MC, Bischoff S, Pollard H. Histamine formation in rat brain during development. J. Neurochem. 1971; 18:1787-1789.

2. Pollard H, Bischoff S, Schwartz JC. Turnover of histamine in the rat brain and its decrease under barbiturate naesthesia. J. Pharmacol. Exp. Ther. 1974; 190:88-99.

Schwartz JC, Barbin G, Baudry M, Bischoff S, Costentin J, Garbarg M, Martres MP, Pollard H, Rose C, Verdiere M. L'histamine comme médiateur dans le système nerveux central. Actualités Pharmacol. 1976; 28:29-61.

4. Pollard H, Bischoff S, Llorens-Cortes C, Schwartz JC. Histidine decarboxylase and histamine in discrete nuclei of rat hypothalamus and the evidence for mast-cells and median eminence. Brain Res. 1976; 118:509-513

5. Bischoff S, Korf J. Different localization of histidine decarboxylase and histamine-N-methyltransferase in the rat brain. Brain Res. 1978; 141:375-379.

6. Bischoff S, Scatton B, Korf J. Biochemical evidence for a transmitter role of dopamine in the rat hippocampus. Brain Res. 1979; 165:161-165.

7. Scatton B, Simon H, Le Moal M, Bischoff S. Origin of dopaminergic innervation in the rat hippocampal formation. Neurosci. Lett. 1980; 18:125-131.

8. Bischoff S, Bittiger H, Krauss J. In vivo (3H)spiperone binding to the rat brain hippocampal formation: involvement of dopamine receptors. European J. Pharmacol. 1980; 68:305-315.

9. Bischoff S, Bittiger H, Delini-Stula A, Ortmann R. Septo-hippocampal system: target for substituted benzamide? European J. Pharmacol. 1982; 79:225-232.

10. Ortmann R, Bischoff S, Radeke E, Buech O, Delini-Stula A. Correlations between different measures of antiserotonin activity of drugs: study with neuroleptics and serotonin receptor blockers. Naunyn Schmiedeberg's Arch. Pharmacol. 1982; 321:265-270.

11. Delini-Stula A, Bischoff S, Radeke E. Antiserotonergic properties of maprotiline and a new antidepressant, oxaprotiline: selective NA uptake inhibitors. Drug Dev. Res. 1982; 2:543-550.

12. Bischoff S, Bittiger H, Krauss J, Vassout A, Waldmeier P. Affinity changes of rat striatal dopamine receptors in vivo after acute bupropion treatment. European J. Pharmacol. 1984; 104:173-176

13. Bischoff S, Bruinink A, Krauss J, Schaub M, Vassout A. In vivo and in vitro characterization of dopamine receptors in hippocampus and their pharmacological relevance. Pharmacopsychiat. 1986; 9:304-305.

14. Bruinink A, Bischoff S. Detection of dopamine receptors in homogenates of rat hippocampus and other brain areas. Brain Res. 1986; 386:78-83.

15. Waldmeier P, Maître L, Baumann P, Hauser K, Bischoff S, Bittiger H, Paioni R. Ifoxetine, a compound with atypical effects on serotonin uptake. European J. Pharmacol. 1986; 130:1-10.

16. Bischoff S, Krauss J, Grunenwald C, Gunst F, Heinrich M, Schaub M, Stocklin K, Vassout A, Waldmeier P, Maître L. Endogenous dopamine (DA) modulates [3H]spiperone binding in vivo in rat brain. J. Receptor Res. 1992; 11:163-175.

17. Bischoff S, Baumann P, Krauss J, Maître L, Vassout A, Storni A, Chouinard G. CGP25454A, a novel and selective presynaptic dopamine autoreceptor antagonist. Naunyn Schmiedeberg's Arch Pharmacol. 1994; 350:230-238.

18. Bischoff S, Barhanin J, Bettler B, Mulle C, Heinemann S. Spatial distribution of kainate receptor subunit mRNA in the mouse basal ganglia and ventral mesencephalon. J. Comp. Neurol. 1997; 379:541-562.

19. Kaupmann K, Huggel K, Heid J, Flor P, Bischoff S, Mickel SJ, McMaster G, Angst C, Bittiger H, Froestl W, Bettler B. Expression cloning of GABAB receptors uncovers similarity to metabotropic glutamate receptors. Nature 1997; 386:239-246 (Plus cover page and News and Views).

20. Auberson Y, Bischoff S, Moretti R, Schmutz M, Veenstra S. 5-Aminomethyl-quinoxaline-2,3-diones. Part I: A novel class of AMPA antagonists. Bioorg. and Med. Chem. Letters 1998; 8:65-70.

21. Acklin P, Allgeier H, Auberson Y, Bischoff S, Ofner S, Schmutz M. 5-Aminomethyl-quinoxaline-2,3-diones. Part III: Highly potent and selective glycine antagonists of the arylamide series. Bioorg. and Med. Chem. Letters 1998; 8:493-498.

22. Kaupmann K, Malitschek B, Schuler V, Heid J, Froestl W, Beck P, Mosbacher J, Bischoff S, Kulik A, Shigemoto R, Karschin A, Bettler B, GABAB-receptor subtypes assemble into functional heteromeric complexes. Nature 1998; 396:683-687.

23. Bureau I, Bischoff S, Heinemann S, Mulle C. Kainate receptor-mediated responses in the CA1 field of wildtype and GluR6-deficient mice. J. Neurosci. 1999; 19:653-663.

24. Bischoff S, Leonhard S, Reymann N, Schuler V, Shigemoto R, Kaupmann K, Bettler B. Spatial distribution of GABABR1 receptor mRNA and binding sites in rat brain. J. Comp. Neurol. 1999; 412:1-16 (plus cover page).

25. Schuler V, Luscher C, Blanchet C, Klix N, Sansig G, Klebs K, Schmutz M, Heid J, Gentry C, Urban L, Fox A, Spooren W, Jaton AL, Vigouret JM, Pozza M, Kelly PH, Mosbacher J, Froestl W, Kaslin E, Korn R, Bischoff S, Kaupmann K, van der Putten H, Bettler B. Epilepsy, hyperalgesia and loss of pre- and postsynaptic GABAB responses in mice lacking GABAB(1). Neuron 2001; 31:47-58.

26. Auberson YP, Allgeier H, Bischoff S, Lingenhoehl K, Moretti R, Schmutz M. 5-Phosphonomethylquinoxalinediones as competitive NMDA receptor antagonists with a preference for the human 1A/2A, rather than 1A/2B receptor composition. Bioorg Med Chem Lett. 2002; 12:1099-102.

27. Volz HP, Moller HJ, Gerebtzoff A, Bischoff S. Savoxepine versus haloperidol. Reasons for a failed controlled clinical trial in patients with an acute episode of schizophrenia. Eur Arch Psychiatry Clin Neurosci. 2002 ; 252:76- 80.

28. Schopfer U, Schoeffter P, Bischoff SF, Nozulak J, Feuerbach D, Floersheim P. Toward selective ERbeta agonists for central nervous system disorders: synthesis and characterization of aryl benzthiophenes. J Med Chem. 2002; 28:1399-401.

29. Renaud J, Bischoff SF, Buhl T, Floersheim P, Fournier B, Halleux C, Kallen J, Keller H, Schlaeppi JM, Stark W. Estrogen receptor modulators: identification and structure-activity relationships of potent ERalpha-selective tetrahydroisoquinoline ligands. J Med Chem. 2003; 46:2945-57.

30. Renaud J, Bischoff SF, Buhl T, Floersheim P, Fournier B, Geiser M, Halleux C, Kallen J, Keller H, Ramage P. Selective estrogen receptor modulators with conformationally restricted side chains. Synthesis and structure-activity relationship of ERalpha-selective tetrahydroisoquinoline ligands. J Med Chem. 2005; 48:364-79.

31. Bischoff, S. Multi-target CNS drug discovery using bio-simulation. Drug Plus International, April-May 2006.

32. Allam, S.L., Bouteiller, J.-M. C., Greget, R., Bischoff, S., Baudry, M., Berger, T.W. EONS synaptic modeling platform : exploration of the mechanisms regulating information processing in the CNS and application to drug discovery. Biomed08, 2008 (in press).

33. Bouteiller, J.M., Baudry, M., Allam, S.L., Greget, R. J., Bischoff, S., Berger, T.W., Modeling glutamatergic synapses: insights into mechanisms regulating synaptic efficacy. J. Integrative Neuroscience 2008; 7(2):185-197.