Synthetische (plakkende) peptiden tegen infectie
Avondlezing door dr. Remko van Leeuwen (Amsterdam, Madam Therapeutics) georganiseerd door de Bossche Chemische Kring.
Samenvatting
The need for new strategies in the treatment of infections is growing as antibiotic resistance (antimicrobial resistance, AMR) is emerging. The incidence of resistance will increase over the years and decades to come, because of the excessive use of traditional antibiotics in both humans and animals. Currently 700,000 annual deaths are contributed to antimicrobial resistance. Estimations tell us that by 2050 AMR will be responsible for about 10 million deaths annually, surpassing cancer and diabetes in annual fatalities. Globally AMR is viewed more and more as a significant public health threat.
Madam Therapeutics, is a near clinical stage biotech company that is developing a new generation of antimicrobial peptides specifically to combat resistant bacterial infections and to prevent and treat infections that are currently left untreated due to the risk of resistance development with current antibiotics.
We call our products Synthetic Antimicrobial and Antibiofilm Peptides (SAAPs). SAAPs are based on technology from Leiden University Medical Centre (LUMC) with whom we have been working closely over the recent years to develop the most optimal peptides, which we are now converting into powerful antibacterial products. SAAPs are highly active against a wide spectrum of bacteria including (multi-) resistant bacteria, are robust against resistance development and have a very favorable tolerance profile.
Our SAAPs are inspired by naturally occurring antimicrobial proteins and peptides, that are produced by all living organisms and can combat bacterial infections, including resistant infections. SAAPS are small, cationic peptides that exhibit a broad range of antimicrobial activities, and often also possess immunomodulatory properties. Moreover, intrinsically, they are also more robust towards resistance development than traditional antibiotics. In the recent O’Niell report on solutions to fight AMR, peptides and their derivatives are ranked amongst the most promising alternatives to traditional antibiotics
DIFFERENT MECHANISM OF ACTION MAKES SAAP’S MORE ROBUST AGAINST RESISTANCE THAN TRADITIONAL ANTIBIOTICS
The development of conventional antibiotics heavily relies on the concept of each antibiotic having a single primary target and a single “biochemical” mode of action like blocking the functionality of a particular enzyme to inhibit bacterial growth. This makes them very vulnerable for the development of resistance against them by the bacteria they are targeting. In contrast, nature has chosen a very different concept for its innate host-defense by means of multi-functional, broad spectrum, anti-microbial peptides. This activity includes disturbing bacterial activity but also inducing mammalian immune responses with a modest potency and a high specificity towards bacteria but a low specificity across bacterial species. Additionally, other activities have been ascribed to such peptides, like wound healing, immunomodulatory and anti-inflammatory characteristics. As a result, antimicrobial peptides have been effective, and remained unchanged throughout the evolution, for billions of years. Therefore, new therapeutic approaches using SAAPs are anticipated to have a longer span of use, beyond the 1–2 decades enjoyed by most conventional antibiotics. SAAPs therefore are excellent candidate agents that subvert a number of Anti-Microbial Resistance mechanisms, and thus are attractive agents to prevent and overcome this problem.
Madam Therapeutics is convinced that the company can address the fast growing and unmet medical need for new (early stage) treatment options for patients suffering from difficult to treat infections due to antimicrobial resistance. Our SAAPs are unique peptides with very specific and highly effective anti-microbial and anti-biofilm activity.
Curriculum Vitae dr. Remko van Leeuwen
Remko van Leeuwen has more than 25 years of research experience under his belt, both in the industry as well as in the academic arena. He has a medical background, and been trained as a clinical epidemiologist and has extensive experienced in clinical infectious disease management. He has obtained a PhD in clinical HIV studies. After completing his PhD, he decided on a career switch and he terminated his hospital based clinical activities. Over the last 2 decades, he has various positions in drug development and clinical trial conduct. He has designed and executed numerous clinical trials and pre-clinical development programs. He has been team leader of large multi-national successful research projects. He carries in depth knowledge of product development, including regulatory requirements, medical affairs, biostatistics and data analysis. He has followed the NIABA Masterclass of Biobusiness 2009/2010. In 2011 he founded Madam Therapeutics.
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