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S E S S I O N S Y N O
P S E S
An Overview of Drug Discovery for
Neurodegenerative Disease
Plenary Speaker
— Barry D. Greenberg, PhD, Principal Scientist,
Neurochem, Inc.
The scope of
discovering, developing and delivering a drug for neurodegenerative
disease is routinely underappreciated by those who have not been
directly involved in pre-clinical research and clinical
development. Success requires an extremely broad and coordinated
multidisciplinary effort. Impacts on success can arise from a large
number of sources, including but not limited to: the qualities of
the biochemical target; tractability of the related medicinal
chemistry; ability to achieve a comprehensible structure-activity
relationship of appropriate chemical series; selectivity and
chemical properties of the prioritized compound(s); the availability
and successful application of informative pre-clinical in vivo
pharmacodynamic models; the compound's metabolism, distribution,
formulation, delivery, and safety; the ability to translate effects
on the target to therapeutically relevant dosing and outcomes in
humans; and the pharmacologic baseline of the patient population
being tested. A discussion of these challenges within a context of
currently considered promising targets for treating
neurodegenerative diseases will be presented.
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SESSION I - Target Identification & Validation:
How Our
Understanding of the Biology of Neurodegeneration Can Be Employed
Chair — Linda
Van Eldik, PhD, Northwestern University
This session
will present the early, exploratory phases of drug discovery.
Speakers will focus on the identification and validation of drug
discovery targets for neurodegenerative disease. Examples of key
questions to be addressed include:
1) Can we
utilize knowledge of the pathophysiology of neurodegenerative
disease, especially Alzheimer's disease, to develop novel
therapeutics that affect disease progression?
2) How are
basic science investigations, such as elucidation of a
macromolecular structure or biological pathway, used as a starting
point for identification of a potential drug discovery target?
3) What is the
process by which drug discovery targets are validated or linked to
the disease?
4) What are the
particular risks inherent in CNS discovery and how can they be
minimized?
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SESSION II - Lead Discovery: In-Vitro Models of
Neurodegenerative Disease
Chair — Ross
Stein, PhD, Harvard Medical School
A key component
of the development of new therapeutic agents is the identification
of molecules that can serve as foundational lead structures on which
drug discovery programs can be built. High-throughput screening of
large collections of drug-like molecules for modulatory activity in
disease-relevant assays is an important means to discovering these
lead molecules. This session will first address general issues of
the development of assays that are suitable for high-throughput
screening and then review specific case studies relevant to
neurodegenerative diseases. The session will end with a discussion
of an academic center that is actively engaged in drug discovery,
development and delivery for neurodegenerative disease and how it
might serve as a model.
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SESSION III - Lead Identification & Optimization:
Unique Aspects of Chemistry in Neurodegenerative Disease
Chair — D.
Martin Watterson, PhD, Northwestern University
This session
will focus on the fundamentals of drug discovery chemistry and how
this can impact or be driven by later-stage considerations of
biology, pathophysiology, and production. Examples of key questions
to be addressed include:
1) What
properties of a chemical compound make it more likely to be useful
as a drug?
2) What
properties are potentially important for bioavailability and CNS
penetrance?
3) How does the
design of a chemical library and screening impact medicinal
chemistry refinement?
4) What are the
standard considerations in medicinal chemistry refinement?
Speakers will
provide a review of fundamentals and stimulate discussion about
these key questions as applied to neurodegenerative diseases,
especially chronic disorders such as Alzheimer’s disease.
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SESSION IV - Pre-Clinical Proof-of-Concept &
Development: Neurodegenerative Disease
Chair — Jordan
Tang, PhD, Oklahoma Medical Research Foundation
Research
designed for pre-clinical proof-of-concept is particularly important
for the development of drugs for neurodegenerative diseases. This is
because neurodegenerative diseases require drugs that can penetrate
the blood-brain-barrier and are also particularly difficult to
assess for efficacy. Proof-of-concept pre-clinical studies are
aimed to critically evaluate therapeutic candidates before embarking
on expensive clinical trials. This session focuses on the overall
requirements and organization of these studies, the necessary steps
leading to clinical trials, and the use and development of
neuroimaging, biomarkers and surrogates in clinical development.
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SESSION V - Drug Delivery Technologies to the CNS
Chair — Illana
Gozes, PhD, Allon Therapeutics & Tel Aviv University
The session is
designed to cover the characteristics of the blood brain barrier and
strategies to enable delivery into the brain. These strategies
include intrinsic drug candidate characteristics, covalent and
non-covalent modifications to enable active transport, and use of
the latest advances in nanotechnology to brain delivery. Systemic
vs. nasal administration approaches will be delineated and
measurements of brain delivery at the analytical and functional
levels will also be addressed.
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SESSION VI - Partnering & Other Models for
Advancing Drug Discovery:
Finding
Resources to Advance Neurodegenerative Disease Drug Discovery
Chair — Elias
Michaelis, MD, PhD, University of Kansas
This session
will discuss how to transition from early-stage drug discovery to
drug development. The speakers will focus their presentations on
the approaches toward drug development and the support available for
such efforts. Examples of key questions to be addressed include:
1) What are the
steps that lead from chemical hit discovery to pre-clinical drug
development?
2) How can
contract research organizations (CRO) and university-based research
centers optimize the process of converting chemical hits to
potential drug candidates, including phrarmacokinetic, oral
bioavailability, drug stability and early toxicology studies, as
well as GMP production of the drug candidates for human studies?
3) What support
is available from the NIH to assist in the conduct of both
pre-clinical and clinical studies of potential new drug entities?
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SESSION VII - Business Development & Technology
Transfer in Neurodegeneration
Chair — Richard
DiRocco, PhD, Secant Pharma
This session
will focus primarily on what academia-based inventors should know to
become effective agents for the commercialization of their
discoveries in the life sciences. Universities are constituted
primarily to disseminate new knowledge, a goal that often is not
consistent with what is required for successful technology
commercialization. Speakers will address issues and questions
relating to:
1) How best to
communicate scientific discoveries, internally and externally, in a
manner that protects the intellectual property rights associated
with the discovery;
2) How to work
effectively with technology transfer professionals;
3) How to
determine the optimal route to commercialization;
4) How to
determine whether a company start-up or a license is most
appropriate for a particular invention;
5) What to
expect from a partnership with a pharmaceutical or biotech company;
and
6) What to look
for in a license and how to get the best deal.
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