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The key issue to be addressed at this conference is the fact that effective neuroprotective agents have not been developed despite extensive, promising, animal research and many clinical trials targeting an assortment of mechanisms in a variety of patient populations.
Key goals of this conference are to explore the reasons this might be the case and discuss how to fashion a proof of principle trial that would test whether a given compound could be an effective neuroprotective agent.
The conference is organized into three main sections:
- Review of basic cellular and molecular mechanisms of neurodegeneration;
- Review of animal models used and results of clinical trials;
- Discussion of new approaches to clinical trials in neuroprotection.
1. Cellular and molecular targets for drug development for neuroprotection
- Acute necrotic injury and excitotoxicity - one set of targets
- Apoptosis - a second target
- Other potential targets - metabolic issues, oxidative damage, free radicals, blood flow, other ions, thermal, etc.
- Discussion: Similarities and differences among different "insults" - Is it rational to mix acute and chronic protection paradigms?
2. Neuroprotection from animal models to clinical trials
- Animal models of global and focal ischemia
- Clinical trials of thrombolytic agents – lessons learned
- Neuroprotection trials in stroke
- Perioperative brain injury trials
- Traumatic brain and spinal cord injury - Animal models/Clinical trials
- Status epilepticus/refractory epilepsy - preventing damage and protecting against epileptogenesis - Animal models/Clinical trials
- Neonatal models - Perinatal encephalomalacia - Animal models/Clinical trials
- Discussion: Why haven't animal trials served as good predictors of human trials
- Alzheimer’s disease - Animal models/Clinical trials
- Parkinson’s disease - Animal models/Clinical trials
- Amyotrophic lateral sclerosis disease - Animal models/Clinical trials
- The neurodegenerative components of psychoses
- Discussion: Relationship between neuroprotection in acute disorders vs chronic
conditions - will one drug/drug combination/strategy likely work for both situations?
- Does mechanism matter?: Is there a way to match a drug with a disease? - Academic and Industry perspectives
3. New strategies for clinical trials in neuroprotection
- Proof of principle trials: which paradigm to choose? - Academic & Industry perspectives
- Appropriate endpoints; duration of neuroprotection trials
- Surrogate markers - Imaging and others
- What kinds of preclinical data are needed to proceed to a clinical trial?
- FDA requirements for different indications
- Clinical trials with drug combinations and drugs approved for other indications
- Economics of neuroprotection trials and creating incentives
- Patent issues related to drugs already on the market or in advanced development
- The challenge of accruing patients in the acute settings
- Ethics and logistics of neuroprotection trials
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