“Hartwig Piepenbrock-DZNE Prize”: EUR 100,000 for brain researchers

Charles Weissmann and Adriano Aguzzi receive award

Joint Press Release: Piepenbrock Group & DZNE

Osnabrück/Bonn, September, 11^th, 2013. Prof. Adriano Aguzzi of the University of Zurich and Prof. Charles Weissmann of the Scripps Research Instit ute Florida (USA) will be awarded the 2013 “Hartwig Piepenbrock-DZNE Prize” for outstanding research in the field of neurodegenerative diseases. Aguzzi’s and Weissmann’s groundbreaking discoveries on the mechanisms underlying prion diseases have major implications for the understanding of other neurodegenerative conditions, including Alzheimer’s and Parkinson’s disease. The prize is awarded by the Piepenbrock Group and the DZNE. The award ceremony will be held in Berlin on September 24^th, 2013.

This year the Hartwig Piepenbrock-DZNE prize has a special significance. It marks the company's 100th anniversary and therefore honors the two winners with 100,000 Euro. But 2013 is also the year where special remembrance is given to Hartwig Piepenbrock who forged this company into one of the largest German family firms. He was diagnosed with dementia several years ago and died on July 3^rd. For many years, he was a great benefactor of the arts, science and society. The prize, sponsored by the Piepenbrock Group, recognizes the outstanding research achievements of Profs. Weissmann and Aguzzi. The winners have been selected by an international panel including highly recognized scientists and representatives from the DZNE and the Piepenbrock family.

Prof. Charles Weissmann (born in 1931) is a Professor Emeritus at the Scripps Research Institute in Florida (USA). The Swiss molecular biologist studied medicine in Zurich and obtained his doctorate in organic chemistry. He completed a postdoctoral fellowship at the School of Medicine of the New York University and subsequently joined the faculty there. In 1967, he returned to the University of Zurich where he assumed the position of Director of the Institute for Molecular Biology. In 1999 he accepted a position with the MRC Prion Unit at the University College London. Five years later he was appointed to the new Scripps Research Institute Florida, where he established and directed the Institute for Infectiology for eight years.

Prof. Adriano Aguzzi (born in 1960) was appointed Director of the Swiss National Reference Center for Prion Diseases at the end of 1995 and has been the Director and a member of the faculty of the Institute for Neuropathology at the University of Zurich since 1997. He obtained his medical degrees in Fribourg and Basel. Following periods at Columbia University, the University of Zurich and the Research Institute for Molecular Pathology in Vienna, he has held the position of Medical Director and Private Lecturer in the fields of pathology and neuropathology at the University of Zurich since 1993. Aguzzi is a citizen of both, Italy and Switzerland.

Pioneers in prion research – Background information
In the 1980s, the public was greatly concerned about human spreading of BSE (bovine spongiform encephalopathy), colloquially called “mad cow disease”. Its rapidly progressive and devastating effects on the brain made the search for the cause of BSE a public health priority. Early work by Tikvah Alper und John Stanley Griffith had postulated that the transmissible agent(s) causing spongiform encephalopathies (scrapie, BSE or Creutzfeld-Jakob disease) could be constituted solely by proteins. In the early 80’s, Stanley B. Prusiner isolated a protein that he predicted would be responsible for neurodegeneration in transmissible encephalopathies. Prusiner named it PRION (from PRotein Infectious ONly) or PrP (prion protein). He formulated the initial hypothesis to explain its toxicity: the interaction between the infective PrP (named PrPSc; Sc=scrapie) and an endogenous protein analogue PrP would convert the latter into a toxic form. Charles Weissmann succeeded in identifying the gene that encodes for PrP in humans and other mammals; this gene and its protein product occur naturally. Weissmann generated transgenic mice lacking the PrP protein, and together with Aguzzi demonstrated that these mice would not develop prion diseases if inoculated with infective material containing PrPSc. In addition, they showed that normal brain grafts implanted in the brain of transgenic mice lacking PrP developed prion pathology whereas the surrounding tissue remained unscathed. This was the strongest evidence that the endogenous protein was required to enable infectivity and neurodegeneration, and provided the most convincing in vivo evidence for Prusiner’s prion hypothesis.

Following these key findings, Weissmann and Aguzzi pursued different research directions. Weissmann directed efforts towards a better understanding of prion infectivity and demonstrated that infectivity can persist on metal (such as that used for surgical tools) after disinfection with formaldehyde – an important discovery for hospital hygiene and safety in laboratories. Moreover, Weissmann and his colleagues pursued investigations of new diagnostic tools and therapeutic avenues.

Aguzzi’s research focused on two key areas: 1. How mutations and/or misfolding of PrP would cause degeneration of nerve cells; 2. How infectious proteins such as PrPSc can reach the brain after ingestion. The first research line, which is still progressing, has identified new mechanisms of prion toxicity. The second has led to major fundamental breakthroughs that are becoming paradigmatic for many neurodegenerative diseases. These include, among others, the discovery of the process of prion neuroinvasion from the gut to lymphoid organs and the peripheral and central nervous system. Perhaps even more important has been the understanding that misfolded proteins can travel from one cell to another and reach multiple sites within the body. These findings are now mirrored in several exciting studies that have discovered spreading and propagation of other misfolded proteins such as amyloid beta and synuclein, which are involved in Alzheimer’s and Parkinson’s disease, respectively. Last but not least, Aguzzi’s research on prion neurodegeneration has led to fundamental discoveries in other research areas such as the origin and function of the follicular dendritic cells in the immune system.

Through their research on prions, Adriano Aguzzi and Charles Weissmann have shown fundamental mechanisms highly relevant to neurodegenerative diseases. Their work provides a solid basis to design new strategies for early diagnosis as well as effective prevention and therapy.

"The outstanding scientific contributions of Charles Weissmann and Adriano Aguzzi are of extraordinary importance for the entire research field of neurodegenerative diseases," comments Prof. Johannes Dichgans, chairman of the selection committee. "With their prion research they have unveiled previously unknown mechanisms that are crucial for many of these diseases, including Alzheimer’s disease and Parkinson’s disease”. A fundamental aspect of these mechanisms is the accumulation of endogenous, misfolded proteins. The work of Aguzzi and Weissmann provides a solid basis to design new strategies for early diagnosis as well as effective prevention and therapy.

The initial work from Weissmann and Aguzzi provided the most convincing evidence that in prion diseases like BSE or Creutzfeld-Jakob disease an endogenous protein is of central importance. They showed that infective material causes nerve cell death only if this particular protein is present. In subsequent work, the research teams led by Aguzzi and Weissmann clarified fundamental mechanisms by which misfolded proteins, such as prions, could cause toxicity. Work from the Weissmann lab has led to the development of new assays for prion replication and toxicity, as well as characterizing sources of infectivity in humans. Aguzzi and his team went on to reveal how prions propagate from cell to cell and finally invade the brain.

Accumulation of endogenous, misfolded proteins is also at the core of other neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Although the cause of misfolded protein accumulation is not an infection as in some prion diseases, the spread of these proteins from cell to cell and within the nervous system seem to follow similar patterns. There is no evidence that other neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease are contagious. The similarity in the underlying mechanisms of disease progression raises common fundamental research questions and suggests future approaches for prevention, diagnosis and therapy.

The Honorees

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