Description
Repositioning
existing drugs for new therapeutic uses is emerging as a new efficient strategy
to drug discovery and is among the most promising strategies for re-engineering
translational science. The use of launched or failed drugs that have already
gone through several steps of the classical R&D process, allows to
significantly reduce development costs, time-to-market and risk of failure.
In fact, despite the enormous advances in our understanding of the molecular mechanisms of diseases, the rate of new drug approvals has remained essentially constant since 1950, while the costs for drug development have dramatically soared. Thus, the validity of current models of drug R&D has been questioned and substantial changes in regulatory science and translational medicine are needed. Identifying new indications for existing drugs is an attractive opportunity, especially for critical areas, such as oncology and neurodegeneration, characterised by the highest attrition rates in the clinical setting. Repositioning has already yielded several successes, including minoxidil for hair loss and sildenafil citrate for erectile disfunction, but also more recent examples such as the rescue of thalidomide through the discovery of its efficacy in both leprosy and multiple myeloma; raloxifene, initially approved for the treatment of breast cancer, then repositioned for osteoporosis, and the anti-depressant duloxetine repositioned for stress-associated urinary incontinence. Analysis of the literature reveals many other examples of approved drugs that are active against multiple targets and can be successfully repurposed for the treatment of neglected or orphan diseases (e.g., Lithium for multiple sclerosis). In addition, the development of novel experimental technologies has led to a better understanding of the involvement of ‘classical’ targets in disease pathophysiology. Thus, re-discovery of targets offers promising avenues for novel R&D approaches. While in the past new applications for existing drugs were mostly found by serendipity, drug repositioning has now turned into a more strategic approach and numerous proof-of-principle studies have demonstrated that in silico technologies, combined with the pre-clinical and clinical validation of the efficacy of existing drugs, may allow successful repositioning.
In fact, despite the enormous advances in our understanding of the molecular mechanisms of diseases, the rate of new drug approvals has remained essentially constant since 1950, while the costs for drug development have dramatically soared. Thus, the validity of current models of drug R&D has been questioned and substantial changes in regulatory science and translational medicine are needed. Identifying new indications for existing drugs is an attractive opportunity, especially for critical areas, such as oncology and neurodegeneration, characterised by the highest attrition rates in the clinical setting. Repositioning has already yielded several successes, including minoxidil for hair loss and sildenafil citrate for erectile disfunction, but also more recent examples such as the rescue of thalidomide through the discovery of its efficacy in both leprosy and multiple myeloma; raloxifene, initially approved for the treatment of breast cancer, then repositioned for osteoporosis, and the anti-depressant duloxetine repositioned for stress-associated urinary incontinence. Analysis of the literature reveals many other examples of approved drugs that are active against multiple targets and can be successfully repurposed for the treatment of neglected or orphan diseases (e.g., Lithium for multiple sclerosis). In addition, the development of novel experimental technologies has led to a better understanding of the involvement of ‘classical’ targets in disease pathophysiology. Thus, re-discovery of targets offers promising avenues for novel R&D approaches. While in the past new applications for existing drugs were mostly found by serendipity, drug repositioning has now turned into a more strategic approach and numerous proof-of-principle studies have demonstrated that in silico technologies, combined with the pre-clinical and clinical validation of the efficacy of existing drugs, may allow successful repositioning.
objectives
To date, very little has been done to promote drug
repurposing in Italy, while forum discussions on this subject are strongly
needed to encourage this promising R&D strategy. Thus, the meeting will be
aimed at promoting interactions between young researchers whose activity is
focused on target re-discovery and drug repurposing for the development of
novel therapeutics. Contributions on basic and clinical pharmacology, as well
as on regulatory issues will be included in order to trace all the crucial paths
of repurposing from bench to market.
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opening lecture
The opening lecture will be held by Dr. Paola Bezzi
from the Department of Fundamental Neurosciences of the University of Lausanne (Switzerland)
and will be focused on “Gliotransmission in health and disease”. Dr. Paola
Bezzi is a
leading expert in the field of glial cell biology and advanced cellular imaging
technologies. For several years, her work has been focused on cellular and
molecular mechanisms governing astrocytic glutamate release. Dr. Bezzi’s
publications demonstrate that, by releasing gliotransmitters with a specific
vesicular apparatus, astrocytes can integrate and process synaptic information
and control or modulate synaptic transmission and plasticity. Her most recent
work has disclosed the molecular mechanisms by which altered gliotransmission
may participate in neurodegenerative diseases. Thus, the molecular machinery
involved in the fine regulation of neuro-glia interaction offers new avenues
for target discovery and validation.
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