Jean-François Rossignol is an American scientist, a medicinal chemist and a physician, born in France on September 5, 1943. He was educated at the University of Paris, later specializing in tropical medicine. He then pursued a career in academia and in the pharmaceutical industry discovering and developing new drugs for the treatment of parasitic diseases such as halofantrine in the treatment of multidrug resistant Falciparum malaria or albendazole and nitazoxanide for the treatment of intestinal protozoan and helminthic infections. In 1993, he co-created his own pharmaceutical company, Romark Laboratories, L.C., to develop his own invention nitazoxanide, the first of the thiazolides. At Romark, he is the Chairman of the Board of Directors of the company and its Chief Science Officer. Following the discovery of the antiviral activity of the thiazolides Rossignol went to Stanford University in California to study interferon stimulated gene pathways and chronic viral hepatitis under Prof. Emmet Keeffe and Prof. Jeffery Glenn. It was in the Glenn laboratory that the mechanism of antiviral activity of nitazoxanide against the hepatitis C virus was discovered.
Education
Rossignol began to study chemistry at the University of Paris under Prof. Paul Cadiot and prepared a doctorate degree in synthetic organic chemistry in the Department of Chemistry of the Radium Institute in Paris, originally the division of Radiobiology and Cancer Research of the Pasteur Institute. Created in 1911 by the Pasteur Institute and the University of Paris, the Radium Institute was the place where two generations of Curies, first Pierre and Marie Curie, later their daughter, Irène Joliot-Curie, and Frédéric Joliot, her husband, discovered natural and artificial radioactivity winning five Nobel prizes between 1903 and 1935. Profoundly marked by the Curie's legacy, Rossignol considered pursuing a career in nuclear physics. The Radium Institute and the adjacent Curie Foundation were also home to a major cancer hospital where Marie Curie and Claudius Regaud had initiated radiotherapy with the radium that Marie had discovered and where the first primitive treatments of cancer were applied, and ultimately, it was Rossignol's exposure to medicine during these years that would kindle his interest and determine his future orientation toward medical research.
Nitazoxanide
Upon the defense of his dissertation in chemistry at the University of Paris, he returned to school to study medicine. During his last year at the Radium Institute, Rossignol had met Raymond Cavier, then Professor of Parasitology at the School of Pharmacy of the University of Paris where he was heading the parasitology laboratory searching for new drugs for the treatment of malaria and intestinal parasites. Cavier had tested some of the compounds Rossignol synthesized for his doctorate degree in chemistry, and he offered Rossignol the opportunity to join his laboratory while continuing his medical education. It would prove to be a good decision, and in 1974 Rossignol and Cavier discovered nitazoxanide, the first of thiazolides. Nitazoxanide was first tested in the Cavier's laboratory and was found effective against both intestinal protozoa and helminths in vitro or in laboratory animals and was first administered in humans in France in the treatment of Taenia saginata and Hymenolepsis nana in a small number of patients.
Work in tropical medicine
Development of Nitazoxanide and Other Thiazolides
In 1993, nitazoxanide was re-invented in collaboration with the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Maryland as the first effective treatment for the emerging apicomplexan protozoa, Cryptosporidium parvum. It was subsequently developed by Romark Laboratories, L.C. in both immunocompetent and immuno-suppressed individuals such as those with AIDS. It would be eventually approved in the United States by the Food & Drug Administration under the trade name of Alinia® for the treatment of non-immunodeficient adults and children from 12 months of age. The serendipitous discovery of the antiviral activity of nitazoxanide and the discovery of its mechanism of action opened a new chapter in Rossignol's life and led to the discovery of an entirely new class of indirect antiviral drugs, acting in stimulating the production of interferons by the host's immune cells activating several interferon stimulated gene pathways known to block viral translation. More intriguing perhaps are the effects of thiazolides on adaptive immunity and more specifically on T Lymphocytes, B Lymphocytes and Natural Killer cells. It is the subject of intense research at Oxford University in the United Kingdom and at the National Institutes of Health in the United States and could lead to a new approach in the treatment of many other diseases such as AIDS but also some cancers or auto-immune diseases. Romark Laboratories quickly initiated the synthesis of hundreds of second generation thiazolides carried out in the United Kingdom at the University of Liverpool under Andrew Stachulski, and new derivatives are now entering clinical development in the treatment of viral diseases such as viral enteritis caused by rotavirus and norovirus, influenza and influenza like illnesses and chronic viral hepatitis B and C. Nitazoxanide, the first of the thiazolides was the first treatment ever discovered for cryptosporidial diarrhea, viral gastroenteritis caused by norovirus and rotavirus and respiratory syncytial virus. It was found safe enough to be given to infants from 2 to 12 months of age.
