Course Overview

Gender Pharmacology: Analgesic and Cardiovascular Drugs

Lecturers: Carla Ghelardini, Laura Sartiani

Gender pharmacology is a research area that developed in the USA starting from the 1980s, studying how gender, male or female, influences the development and impact of diseases and the response to therapy. This is a new, cross-cutting dimension of pharmacology which, by first assessing gender differences in the physiology, pathophysiology, and clinical aspects of many diseases, aims to reach therapeutic decisions based on scientific evidence for both men and women. According to the principles of gender pharmacology, men and women respond differently to certain therapies.

Animal Experimentation: Current Legislation

Lecturer Alessia Melani

In Italy, the use of animals for scientific purposes is regulated by Legislative Decree of March 4, 2014, no. 26 “Implementation of Directive 2010/63/EU on the protection of animals used for scientific purposes.” This course will illustrate the current legislation and alternative methods, a term used to indicate all procedures aimed at reducing the use of animals, completely replacing them in experimentation, or limiting or eliminating their suffering. In particular, the principles of Replacement, Reduction, and Refinement will be presented.

Biotechnological Drugs in Pediatrics

Lecturer Gabriele Simonini

Drug therapy for numerous pediatric diseases, including autoimmune and chronic inflammatory disorders such as rheumatologic diseases, has drastically changed in recent decades. A better understanding of pathophysiological mechanisms has led to the development of biotechnological drugs, which, unlike classical immunomodulating drugs that act on the entire immune system, target specific molecules of inflammatory activity such as cytokines (e.g., TNFα). To date, biotechnological drugs have revolutionized the prognosis of these patients, with excellent safety profiles.

Pathophysiology and Pharmacology of Pain. Mechanisms Involved from Youth to Old Age

Lecturers Nicoletta Galeotti, Lorenzo Di Cesare Mannelli

The lectures examine different types of pain, including nociceptive pain, neuropathic pain, and psychogenic pain, along with their targeted therapies. Pharmacological treatment of pain includes various therapies, such as natural and synthetic drugs, nutraceuticals, physical therapies, behavioral therapies, and invasive therapies like surgery. Analgesics can be prescribed for mild or moderate pain, while more potent drugs such as opioids may be needed for severe pain. The therapeutic approach to pain varies depending on the type of pain and also on patient frailty, with therapy tailored primarily by age. Pediatric pain must consider the incomplete development of the nervous system, which does not reduce sensitivity but rather makes modulation more difficult.
An as-yet unsatisfactory amount of clinical experimentation dedicated to pediatric age limits therapeutic possibilities, often adapting adult therapies to children. A different scenario emerges in those over 65. A typical feature of aging is the aberrant accumulation of senescent cells in organs and tissues, which can foster the development of age-related diseases, including neurodegenerative conditions accompanied by pain. Counteracting cellular senescence may represent an additional approach for effective pain management. Understanding the cellular basis of senescence is an important step toward identifying targeted therapies.

Antitumor “Magic Bullets” in the 21st Century

Lecturer Stefania Nobili

Starting from the concept of “Magic Bullets” expressed by Paul Ehrlich in the early 20th century in reference to substances with selective toxicity—at that time essentially against pathogens—the course will focus on progress made in recent years in terms of selective toxicity of new antitumor drugs as well as future prospects in this therapeutic area. The course will discuss antitumor drugs with innovative mechanisms of action currently available in clinical practice, acting at the level of tumor cells or the tumor microenvironment cells. Specifically, signal transduction inhibitors (protein kinase inhibitors and monoclonal antibodies) and immunotherapies, with particular reference to immune checkpoint inhibitors and CAR-T cells, will be addressed. For these drugs, the role of specific molecular targets and molecular alterations such as mutations, fusions, and gene amplifications in their antitumor activity will be highlighted. Innovative therapeutic strategies that have reached clinical trials in tumors (e.g., RNA-based drugs, protein degraders) will also be discussed.

Substance Use Disorder and Neurodevelopment

Lecturer Guido Mannaioni

This lecture series focuses on substance use disorder (SUD) and some specific damages induced by exposure to xenobiotics, especially during the perinatal period. The developing brain is particularly vulnerable to xenobiotics, with resulting physical, learning, and behavioral disorders in newborns. The lessons will focus on experimental models of perinatal neurodegeneration and neurodevelopment, as well as on persistent molecular alterations of neuronal circuits that may underlie numerous childhood pathologies.

Cortical Developmental Anomalies – Channelopathies and Forms Associated with Movement Disorders

Lecturer Renzo Guerrini

The course will address the pathogenetic mechanisms of epileptic encephalopathies, with reference to etiological heterogeneity and variable pathophysiological implications. It will particularly cover the involvement of various neuronal functions as a consequence of specific genetic mutations, the pathophysiology of epileptogenesis, the comorbidities associated with developmental encephalopathies, and the current diagnostic and precision medicine challenges. Specific examples will be provided to illustrate the role of the most advanced diagnostic techniques available in this field, with reference to molecular medicine, electrophysiology, and high-field imaging.

Chronic Inflammatory Bowel Diseases as a Model for Non-Communicable Chronic Diseases

Lecturer Paolo Lionetti

The course aims to study the human microbiota of industrialized Western societies, which substantially differs from the ancestral microbiota still found in rural populations of developing countries. Analysis of the microbiota of children and families living in rural areas of Burkina Faso who undergo urbanization and dietary changes has shown substantial differences in fecal microbiota composition. Rapid modernization, antibiotic use with the acquisition of resistant species, and dietary changes with the adoption of Western dietary patterns characterized by consumption of animal proteins, saturated fats, simple sugars, additives such as emulsifiers and carrageenan, and reduced fiber intake have led to substantial changes in microbiota composition. These changes cause a direct pro-inflammatory effect at the intestinal mucosa, which, besides nutrient absorption, also represents an important lymphoid organ. The Western diet also causes a progressive reduction of bacterial species capable of degrading fiber and producing anti-inflammatory metabolites such as short-chain fatty acids (SCFAs). Furthermore, it compromises intestinal permeability and reduces the thickness of the intestinal mucus, contributing to the development of a “leaky gut.” In the intestinal mucosa, particularly in the terminal ileum, differentiation of T and B lymphocytes with immunological memory occurs, crucial both in the immune response against pathogens and in the induction of immune tolerance. In genetically predisposed individuals, microbiota alterations and the mild inflammatory state caused by diet may lead to the development of a self-perpetuating state of chronic intestinal inflammation.

Experimental Design and Dedicated Software: Optimization in the Pharmaceutical Field

Lecturer Serena Orlandini

The course will present the basic principles of experimental design for studying screening and optimization issues in the pharmaceutical field: selection of responses and factors, choice of a regression model, selection of the experimental matrix, execution of experiments, calculation of model coefficients, and statistical analysis of data. Dedicated software (NEMRODW-LPRAI and MODDE-Sartorius) will be demonstrated to illustrate how to plan experiments, interpret regression models and related graphs, and identify optimal conditions.

Chemical Profiles and Nutraceutical Properties of Common Foods, Novel Foods, and Botanical-Based Supplements

Lecturers Nadia Mulinacci, Marzia Innocenti, Maria Bellumori

Methods applied to the study of the composition of complex plant extracts will be illustrated. Examples will be discussed in which very different chemical structures are co-present, with a focus on approaches to quantifying co-existing molecules in the absence of pure standards. It will also be discussed how the chemical profile of extracts can be correlated to the activities observed in biological tests.

Walking through the fundamental steps of homology modeling, the activity guides learners to obtain the three-dimensional structure of targets and to assess their quality for reliable use in the rational design of molecules in drug discovery projects.

Innovative Formulations

Lecturers Anna Rita Bilia, Maria Camilla Bergonzi, and Francesca Maestrelli

The course will illustrate the principles underlying the design, preparation, and control of the main unconventional pharmaceutical dosage forms for administering natural and synthetic substances.

Chemistry and Pharmacology of Biopharmaceuticals: New Frontiers

Lecturers Paolo Rovero and Cristina Luceri

The most innovative aspects of the chemistry and pharmacology of biological drugs and advanced biological therapies will be presented and discussed, with particular reference to monoclonal antibodies, their most advanced engineered variants, and nucleotide-based drugs.

Drug Design of Metalloenzyme Inhibitors with Therapeutic Applications

Lecturer Claudiu T. Supuran

The lectures will describe the structure, function, and drug design of inhibitors of enzymes containing zinc, magnesium, or nickel ions. Examples of drug design, clinically used agents, and clinical candidates will be provided and discussed.

New Strategies in Pharmaceutical Chemistry

Lecturers Maria Novella Romanelli and Elisabetta Teodori

This seminar series aims to introduce PhD students to topics covered in recent chemical–pharmaceutical literature. Possible themes to be explored include, for example, the design of innovative drugs, structural modifications to target drugs to specific body districts, new molecular targets, and new trends in the assessment of drug-like properties.

Development of New Drugs for the Therapy of Neurodegenerative Diseases

Lecturers Vittoria Colotta and Daniela Catarzi

The course will address recent chemical–pharmaceutical developments of disease-modifying agents for the therapy of multifactorial neurodegenerative disorders such as multiple sclerosis, Parkinson’s disease, and amyotrophic lateral sclerosis. Insights will be provided on modulators of emerging targets, with a focus on kinases and sphingosine-1-phosphate receptors.

Advanced Applications of Mass Spectrometry in the Study of Bioactive Molecules

Lecturer Gianluca Bartolucci

The course includes: fundamental concepts of mass spectrometry; complex experiments in mass spectrometry and accurate mass measurements. Applications in the pharmaceutical field and applications in the nutraceutical field.

Neurophysiology

Lecturer Paola Binda

The objectives are to promote advanced knowledge of electrophysiology techniques used in neuroscience research, with particular attention to those employed in the cognitive neurosciences, both in animal models and in humans, during development and in adulthood. For each technique, the advantages and disadvantages in different experimental designs will be discussed, and recent developments will be highlighted. Recent scientific papers using electrophysiological techniques in the field of Cognitive Neuroscience will be analyzed in depth, particularly those addressing the same problem with different techniques, in order to foster PhD students’ ability to critically evaluate the scientific literature in the field.

Molecular Imaging for Neuroscience in Animals and Humans

Lecturers Roberto Sciagrà and Giuseppe De Vito

This course, in its first module, aims to enable students to define and recognize the different optical microscopy techniques commonly used for animal studies, particularly in neuroscience. By the end of the course, students will understand and be able to explain how these techniques work, so as to apply the most suitable optical microscopy method to each experimental contingency. To this end, students will be able to confidently compare the different techniques, highlighting their strengths and weaknesses in various applications, and manage them competently in both practical and theoretical terms.

Statistical Mediation and Moderation

Lecturer Maria Anna Donati

The course aims to foster autonomy in conducting and interpreting mediation and moderation analyses within the general linear model. Specifically, after consolidating the necessary statistical prerequisites, the course aims to teach PhD students to verify the statistical conditions of research data that allow hypothesizing mediation/moderation models in light of the relevant literature; to test these hypotheses by conducting analyses using R software; to interpret the meaning of the results obtained; and to draft a scientific report. In detail, the specific topics for mediation include: total, direct, and indirect effects; size of the indirect effect; simple and multiple mediation; while for moderation the specific topics include: moderated effect and interaction, considering both continuous and categorical moderators.

Neurometabolic Diseases

Lecturer Amelia Morrone

TRP Channels

Lecturer Francesco De Logu

The course will introduce and delve into “Transient Receptor Potential” (TRP) channels, which belong to a family of ion channels with a crucial role in sensory and pain signaling. The structure, expression in cellular systems, and neuronal and glial localization of these ion channels will be covered, as well as their role in the development of pain and neuroinflammation, migraine, and chronic pain.

Drugs and Memory Disorders: Molecular Mechanisms Underlying Memory Processes

Lecturer Anna Maria Pugliese

The course aims to provide the essential and up-to-date elements for an introduction to basic neurobiology and neuropharmacology. The following lectures will be covered: Drugs and memory and in vitro models of memory and learning (2 hours); Anticonvulsant and antiepileptic drugs (2 hours); Antidepressant drugs and experimental models of this pathology (2 hours).

Preclinical Models for the Development of New Pharmacological Therapies in Autism Spectrum Disorder

Lecturer Alessio Masi

Autism spectrum disorder is a neurodevelopmental condition with genetic and environmental causes. Patient studies have highlighted a large number of risk factors on the basis of which numerous experimental models have been developed. The lecture will present the main animal and cellular models used to study the biological mechanisms underlying the various forms of autism, as well as some examples of using these models as platforms for the discovery and development of new drugs.

Treatment of Rheumatoid Arthritis: Classical Aspects and New Frontiers

Lecturer Letizia Crocetti

The topic concerns current therapies for the treatment of rheumatoid arthritis (RA) and the most recent advances in this field. Information is provided on the features of RA, its epidemiology and disease-related causes of death, etiopathogenesis, risk factors, clinical course, systemic consequences, and diagnosis. The largest section addresses the description of drugs currently in use, with particular attention to Disease-Modifying Anti-Rheumatic Drugs (DMARDs), analyzing their three classes: Conventional Synthetic DMARDs, Biologic DMARDs, and Targeted Synthetic DMARDs. A brief overview is planned on drugs currently in clinical trials for RA and on the most interesting findings from recent literature. Specifically, medicinal chemistry studies on biological systems involved in the development and progression of RA are reported, with particular attention to new promising targets.

Quality by Design in Process Development and Understanding

Lecturer Sandra Furlanetto

In the pharmaceutical field, quality is a fundamental concept for the safe, effective, and proper use of medicines. It is therefore important to know the product characteristics that potentially influence it, known as Critical Quality Attributes (CQAs). CQAs can vary greatly depending on the product development stage, and Quality by Design (QbD) can be used for their optimization and monitoring. QbD employs multivariate experimental design strategies and, through predefined objectives, enables process understanding and control by defining the “design space,” i.e., an experimental space where the quality of the overall process is guaranteed at a fixed probability level. The lecture will address QbD applications in analytical and pharmaceutical technology, with particular attention to the development of analytical methods for quality control.

From the Discovery of Solid-Phase Synthesis to the Development of New Drugs: Half a Century of Peptide Chemistry from a Pharmaceutical Chemist’s Perspective

Lecturer Paolo Rovero

The family of therapeutic peptides now includes several dozen approved drugs, while many others are in various stages of clinical development. These achievements have been enabled by the spread and optimization of solid-phase peptide synthesis techniques, introduced by B. Merrifield in the second half of the last century and subsequently widely developed, thus allowing both extensive structure–activity relationship studies to obtain new peptide drug candidates and their subsequent large-scale GMP production.

Multitargeting Approaches Involving Carbonic Anhydrase Inhibitors/Activators: Hybrid Drugs Against a Variety of Disorders

Lecturer Claudiu Trandafir Supuran

Carbonic anhydrases are enzymes involved in numerous diseases, and their inhibitors are used clinically as drugs for the management of glaucoma, epilepsy, obesity, and tumors. Activators are less studied, but in the last decade promising applications have emerged for the treatment of memory, recognition, and fear-memory disorders, as well as emotional memory and various cognitive/degenerative disorders. In the last decade, multitargeting approaches have been proposed by hybridizing CA inhibitors (CAIs) with NO donors, CO donors, prostaglandin analogs, β-adrenergic blockers, non-steroidal anti-inflammatory drugs, and a range of antitumor agents (cytotoxic drugs, kinase/telomerase inhibitors, P-gp and thioredoxin inhibitors). Many of the resulting hybrids have shown greater efficacy than their parent drugs, making multitargeting an effective and innovative approach for several pharmacological applications. All classes of CA inhibitors and activators will be considered, with their inhibition/activation mechanisms discussed in detail.

Ligands of Cannabinoid Receptors (CB1 and CB2)

Lecturer Claudia Vergelli

Stereochemistry in Drug Design

Lecturer Fabrizio Carta

The course includes: fundamental concepts of stereochemistry; effects of isomers in biochemistry/enzymology; stereocontrolled transformations applied to the synthesis of molecules/macromolecules of biochemical interest.

Basic Neurobiology

Lecturer Elisa Castaldi