Introduction for the Fifth International Symposium on Thymosins in Health and Disease

KEYWORDS:

• Thymosins
• symposium
• Health and Disease
• translational advances

The Fifth International Symposium on Thymosins in Health and Disease brought together many of the leading scientists, clinicians, and thought-leaders from the United States, Europe, China, Japan, Israel, and South America to discuss the latest advances and clinical applications of the thymosins in both basic and clinical areas. The symposium, held in Washington, DC, on 15–17 November 2017, was jointly sponsored by the George Washington University and the University of Rome ‘San Raffaele.’

The six plenary sessions were devoted to advances in basic research and translational advances in the areas of immune deficiency diseases, AIDS, infectious diseases, cancer, wound healing, and in the treatment of cancer, cystic fibrosis, dry eye, severe sepsis, cardiovascular diseases, hepatitis B, and neurological pathways, including trauma, stroke, and peripheral neuropathy.

Enrico Garaci [1], MD, the Rector of the University of Rome ‘San Raffaele’ and Gabriel Sosne [2], MD, Associate Professor at the Wayne State University School of Medicine and the Kresge Eye Institute gave keynote lectures and were corecipients of the 2017 Abraham White Distinguished Science Award. Peter J. Hotez [3], MD, PhD, Dean of the National School of Tropical Medicine at Baylor University College of Medicine was the recipient of the 2017 Abraham White Public Service Award.

Enrico Garaci was honored for his pioneering studies and scientific contributions which have significantly advanced our understanding of the role of thymosin α1 (Tα1) on the immune system and has led to the development of new approaches in the treatment of infectious diseases, cancer, and cystic fibrosis. For over four decades as an educator and a scientist, Dr Garaci’s laboratory has been at the cutting edge of the rapid advances in the field of immunology.

As President of the Committee for Biology and Medicine of the National Research Council (C.N.R), he encouraged the development of biomedical research in Italy through the development and funding of many cutting edge areas of science as outlined in the program. These projects have engaged thousands of scientists from Italian universities, industries, and research institutions. The aim of these projects was to concentrate the efforts of the many different research bodies and channel them to accelerate scientific discovery which has led to new drugs, new technologies, and improvement of therapies for many diseases. Thanks to his leadership, Italian science has been at the forefront of many advancements in the treatment of disease.

Gabriel Sosne was honored for his pioneering studies and scientific contributions which have significantly advanced our understanding of the mechanism of action and role of thymosin β4 (Tβ4) in the treatment of diseases and injuries of the eye, including dry eye and neurotrophic keratopathy. His inspired leadership as a scientist and as a physician has significantly advanced our understanding of the potential role of Tβ4 in the clinic. His laboratory discoveries have provided the scientific foundation for clinical trials of Tβ4 currently underway in the United States.

Dr Sosne is the recipient of a number of prestigious awards, including the 2011 Carl Camras Translational Research Award from ARVO, and the 1994 Samuel Raucher Award for Excellence in Medical Studies. In the tradition of Dr Abraham White, Dr Sosne has been an example to his students and colleagues of the importance of scientific cooperation and collaboration as a mode of accelerating scientific discoveries.

Peter Hotez was honored for his lifetime of scientific and medical accomplishments in advancing the development of novel vaccines to treat neglected tropical diseases, and for his outstanding public service which has the potential of significantly improving the health and quality of life for hundreds of millions of people of the Earth with limited access to health care

Dr Hotez is the founding Dean of the National School of Tropical Medicine where he is a professor of Pediatrics and Molecular Virology & Microbiology at the Baylor College of Medicine. He is also the director of the Texas Children’s Center for Vaccine Development (CVD) where he holds an Endowed Chair of Tropical Pediatrics. He is also University Professor at Baylor University, and Fellow in Disease and Poverty at the James A Baker III Institute for Public Policy.

Dr Hotez is an internationally recognized physician–scientist in neglected tropical diseases and vaccine development. As head of the Texas Children’s CVD, he leads the only product development partnership for developing new vaccines for hookworm infection, schistosomiasis, and Chagas disease, and SARS/MERS, diseases affecting hundreds of millions of children and adults worldwide.

1. The conference scientific summary

The papers included in the volume of these proceedings highlight the significant progress that has occurred in our understanding of the role of the family of thymosin peptides in health and disease since the last International Symposium on Thymosins in Health and Disease held in Rome in 2014. The papers summarize the most recent advances in basic research, including mechanisms of action, which have provided the scientific foundation for translational studies with Tα1, Tβ4, and Prothymosin ɑ (ProTɑ). In this volume, there are several reports describing novel formations, diagnostic advances, as well as descriptions of boron conjugates of Tβ4 and novel nanoparticles and their potential in the treatment of infectious diseases.

Plenary session I focused on the preclinical and clinical studies with Tα1 involving immune modulation, infectious diseases, septic shock, and cystic fibrosis. Immune modulation studies found that patients who were unhealthy with non-small cell lung cancer had significantly low levels of Tα1. Clinical studies also described the positive effects of Tα1 in the treatment of patients with septic shock, hepatitis B virus-compensated cirrhosis, and pancreatitis; Tα1 was also shown to be a single molecule drug with potential to stop the progression of cystic fibrosis and to play a role in the treatment of the disease.

Plenary session II was devoted to the potential clinical applications of Tβ4 in infectious diseases, sepsis, liver and kidney fibrosis, and Alzheimer’s disease. Thymosin Fraction V was found to have over 100 monoisotopic masses that were precursors of novel peptides, including ubiquitin. Tβ4 was shown to improve clinical treatments for bacterial keratitis through wound healing and activation of pro-resolving pathways. Similarly, studies showed that Tβ4’s anti-inflammatory properties may be useful in the treatment of alcoholic liver injury, kidney disease, and Alzheimer’s disease. Additionally, low Tβ4 levels and high F-actin levels were analyzed as potential novel biomarkers to document severe sepsis.

Plenary session III focused on the mechanism of action of thymosin peptides, tissue regeneration, receptors, signaling, brain trauma, and neurorepair and protection through nanoparticle platforms. Studies were presented highlighting the potential role of nanoparticles with predetermined loads of peptides as vectors of more efficient activity. ProTɑ was reported to play a key role in brain robustness against lethal stress. It was reported that Tβ4 treatment significantly reduced infarct volume among stroke aged rats, and the peptide was found to improve neurologic function through the induction of tissue remodeling due to its anti-inflammatory properties. Additionally, miRNA’s miR-200a-3p and miR-200b-3p were identified as biomarkers that could serve as diagnostic tools for patients who respond to Tβ4.

Plenary session IV looked at the interactions between Tβ4 and the cardiovascular system, focusing on mechanism of action, vascular effects, and stem cells. Tβ4 was shown to mediate vascular protection through interaction with low-density lipoprotein receptor-related protein 1, as well as to improve the differentiation and vascularization of engineered heart tissue’s through an increase of expression of cardiac proteins. In one study, Tβ4 was shown to protect cardiomyocytes from hypertrophic responses by targeting WISP-1. Another interesting study found capillary growth in vivo as a result of post-ischemic Tβ4 administration. Additionally, Tβ4’s ability to reactivate Wt1 was expanded upon by a study that reported the in vivo requirements for epigenetic reprogramming with Tβ4.

Plenary session V dealt with the thymosin peptides in relation to autophagy, multiple sclerosis (MS), chronic granulomatous disease, immune regulation, psychoneuroimmunology, and allergy. Tα1’s anti-inflammatory capabilities were reported to be a novel new potential treatment in MS targeting B cell responses. In studies on autophagy, thymosins were shown to act as regulators of proteostasis networks that can rescue mutant protein trafficking to control inflammation and activate tissue repair and remodeling. The clinical applications for allergy were discussed as another potential use of thymosins’ anti-inflammatory capabilities.

Plenary session VI contained all late breaking papers, which focused on the thymosin peptides, clusters, combination therapy, mechanisms of action, and the development of a novel HIV vaccine. Tα1 was reported to directly interact with a protein involved in cancer aggression, leading to a new anticancer activity. New combination therapies were reported in studies with Tα1 and IRX-2, as well as Tα1 and PD-1. In cancers, Tα1 was studied to give patients an improved progression time in non-small cell lung cancer, and to improve long-term survivability of metastatic melanoma. A tracking study illustrated that the attachment of a selected boron cluster to Tβ4 could prolong the half-life of the peptide and enhance therapeutic effects. Finally, a study was reported where a novel ultraviolet-inactivated HIV preparation paved the way for a potential polyvalent preventative HIV vaccine.

The increasing number of synthetic thymosin peptides and analogs available has significantly accelerated animal model experimentation in the field and has helped researchers to consider novel clinical applications. These proceedings should be of keen interest to both basic and clinical scientists, as well as pharmacologists, immunologists, biochemists, and cell biologists with interests in utilizing thymosin peptides to modulate immune responses. It should also be of special interest to physicians and other health-care workers studying the clinical applications of the thymosins in both health and disease.

Declaration of interest

The authors are very appreciative of the generous support provided by the following organizations and individuals: The George Washington University; University of Rome ‘San Raffaele’; RegeneRx Biopharmaceutical, Inc; SciClone Pharmaceuticals, Inc; Steve Papermaster; The Finkelstein Foundation; G-Tree Pharmaceuticals Co, Ltd; Lee’s Pharmaceutical; Shu-Kuang Hu and Jyishyang Liu, Ora, Inc; Rothwell Figg Ernst & Manbeck, P.C.; Bachem, & PolyPeptides Laboratories, Inc. Without the support from our friends in the private sector, this type of educational meeting would not be possible. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Acknowledgments

We would like to thank the program committee: Mahnaz Badamchian, Michael Chopp, Cartesio Favalli, Ewald Hannappel, Hynda Kleinman, Tim McCaffrey, Dan Morris, Paul Naylor, Anna Teresa Palamara, Luigina Romani, Deepak Srivastava, Gabriel Sosne, Christian Kupatt, Hiroshi Ueda, and Crystal Qin for their help in planning this important scientific symposium. We would also like to acknowledge the editorial staff of the Expert Opinion for their support in editing and publishing this issue.