Harnessing drug resistance: development of innovative drugs against bacterial and parasite infections and against microbial drug resistance.
NatSynDrugs is an European Technology Platform, based on public-private partnerships, and represents a new paradigm for drug development for novel antimicrobial and antiparasitic agents, for the prevention and treatment of infectious diseases, and for the study of the evolution, mechanisms, and transmission of resistance. The spread of resistant bacteria, leading to untreatable infections, is a major public health threat but the pace of antibiotic discovery to combat these pathogens has slowed down. Moreover, resistance to artemisinin is now expanding and may spread rapidly as for chloroquine resistance, now present everywhere in malaria-ridden regions. The scenario is asking for effective and urgent countermeasures. NatSynDrugs encompasses Italian and European Universities and Research Institutes that have a major commitment to the development of drugs against bacterial infections, malaria and other parasitic infections. Medicinal chemistry and biology of infectious diseases are scientific disciplines undergoing rapid development. The new frontiers of molecular biology, the new technologies for drug design and the recent progresses on genomic and proteomics have created exciting working fields for scientists involved in drug discovery and development for the treatment of infectious diseases.
Novel approaches to cancer therapy. Modulators of the antiangiogenetic process and apoptotic drugs from natural and synthetic sources capable to inhibit microtubule dynamics.
The growing incidence of neoplastic pathologies and the fact that drug resistance and toxicity represents the most important clinical problems associated with the common anticancer strategies, drive the scientific community to search for novel therapeutic tools characterized by an improved efficacy and safety. NatSynDrugs is involved in the development of “targeted therapy”, a term which refers to a new generation of cancer drugs designed to interfere with a specific molecular target believed to have a critical role in tumor growth, progression and drug resistance. Inhibition of microtubule dynamics is the main focus to develop new drugs to be used in multidrug regimens for the therapy of several solid tumors.
Discovery of innovative drugs and diagnostic agents for neurodegenerative and protein conformational diseases.
Neurodegeneration is a general term that includes neurodegenerative diseases, such as Alzheimer’s, Parkinson’s and Huntington’s diseases, multiple sclerosis, and amyotrophic lateral sclerosis (ALS). Alzheimer’s disease (AD) is the leading cause of dementia amongst older people. With the greying of the European, North American and Asian population, AD is expected to reach epidemic proportions over the next two decades, which makes the development of new therapeutic strategies and effective drugs essential. Although some therapeutics are available, the lack of diagnostic agents is making difficult the early identification of AD. Neurons are not readily regenerated and excessive neuron damage or loss can have devastating effects on an individual. Few or no effective options are available for their treatment. No effective therapeutic and diagnostic agents are available to date for the Creutzfeldt-Jakob syndrome, a pathologic conditions depending upon an abnormal folding (misfolding) of the protein prion, and together with Alzheimer’s disease has been named “Protein Conformational Disease” (PCD). NatSynDrugs mainly focuses on the development of innovative drugs and diagnostic agents for Alzheimer’s disease and prione diseases, and of novel therapeutic approaches to amyotrophic lateral sclerosis (ALS).
Innovative drugs for the treatment of HIV and HCV infections
Acquired Immunodeficiency syndrome (AIDS) is a pandemic disease affecting several millions of adults and children in the developed, underdeveloped and developing countries. Although this disease still remains a major social problem in several countries, and the definitive cure is not currently available, in the last ten years impressive progress has been made in the treatment of AIDS infective patients. The multidrug therapy (or “drug cocktail”) provides a substantial delay in disease progression compared to monotherapy or dual therapy, allowing significant immune system function restoration, and retarding the emergence of resistant viral strains. However, the possible development of resistance, with reduction of therapeutic options in the case of unsuccessful regimens, accounts for a continue development of new, potent, broad-spectrum antiviral agents. Hepatitis C virus (HCV) infection is an emerging global epidemic, concerning about 170 million people worldwide. Due to the infection the patients can develop a chronic hepatitis, liver cirrhosis and end-stage liver diseases. No effective cure is available to date. Interferon-alpha (INT) and pegylated INTs, in combination or not with ribavirin, proved to be scarcely effective in no more than 50% of chronically infected patients. Consequently, new and better therapeutic strategies are needed. HCV non structural protein NS3 helicase domain is a promising target to develop novel therapeutics.
Drug development for neuropsychiatric disorders
Neuropsychiatric disorders represent the second largest cause of morbidity and premature mortality worldwide. These disorders include anxiety, schizophrenia, bipolar disorder, obsessive-compulsive disorder. Schizophrenia is one of the major neuropsychiatric disorders, characterised by severe and chronic mental impairment. This devastating disease affects 1% of the world’s population. Symptoms begin in early adulthood and are followed by a period of interpersonal and social dysfunction. The complexity of the disorder, due to a wide array of symptoms, has hampered those efforts with the aim of discovering an ideal agent for the pharmacological treatment of schizophrenia. NatSynDrugs is involved in the discovery and development of innovative atypical antipsychotics based on the exploitation of the dopaminergic, serotoninergic and glutamatergic neurotransmission systems.