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An
Overview of Drug
Discovery for
Neurodegenerative
Disease
Plenary Speaker — Howard
Fillit, MD, ADDF
The scope of discovery,
development and delivery
of a drug for
neurodegenerative
disease is often
under-appreciated by
those who have not been
directly involved in
pre-clinical research or
clinical development.
Success in this field
requires an extremely
broad and coordinated
multidisciplinary
effort. Impediments to
success can arise from a
large number of
sources. A discussion
of these challenges
within a context of
current targets for
treating
neurodegenerative
diseases will be
presented.
Session I.
Basics of Medicinal
Chemistry
Chair — D. Martin
Watterson, PhD,
Northwestern University
This session will focus
on the fundamentals of
drug discovery chemistry
and how this is driven
by later-stage
considerations of
pharmacokinetics,
pathophysiology and
production.
Introductory lectures
will address what
physical and biological
features make a chemical
scaffold or small
molecule “drug-like”,
and the potential impact
of considering such
properties on selection
of compound libraries
for screening and the
follow-up medicinal
chemistry refinement.
The lectures will also
introduce key concepts
of medicinal chemistry
refinement, with
emphasis on CNS drug
discovery, used in
taking a screening hit
into a lead compound
and, eventually, into
selection of a candidate
for drug development.
These introductory
lectures will be
followed by three case
studies representing
different classes of
single molecular CNS
targets that will
demonstrate the
application of these
principles to project
design and management.
At the end of this
session, participants
should have familiarity
with key concepts that
are used in small
molecule compound
selection, and
understand the general
processes involved in
medicinal chemistry
refinement in early
stage CNS drug
discovery.
Session II.
Hits & Leads: Early
Phases of Drug Discovery
Chair — Marcie Glicksman,
PhD, Harvard Medical
School
A key component of the
development of new
therapeutic agents is
the
identification of
molecules that can serve
as initial 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
strategies for the
development of assays
that are suitable for
high-throughput
screening and then
strategies for secondary
assays to validate the
primary screening
results. Most drug
development efforts fail
due to toxicity and ADME
(absorption,
distribution,
metabolism
and
excretion)
properties. This session
will end with a
presentation on
technology used for
in vitro toxicity
and ADME testing.
Session III.
Pre-Clinical
Proof-of-Concept &
Development
Chair — Edward Spack,
PhD, SRI International
The focus of this
session is the
transition from lead
compound to clinical
testing, the scenic
stretch of drug
development often
referred to as the
“Valley of Death”.
Several factors converge
to kill promising
compounds at this
translational stage,
including lack of
funding/resources/expertise,
the delivery challenge
of the blood brain
barrier and common
problems of toxicity,
manufacturing and
formulation. Drawing on
examples of past
successes and failures,
this series of
presentations will chart
the course from lead
optimization to
initiation of clinical
testing, highlighting
emerging models for
internal development,
outsourcing and
funding. Few
investigators or new
companies who survive
this pre-clinical phase
travel the clinical path
alone. Therefore the
pre-clinical decisions
that support or hinder
partnering will also be
presented.
Session IV.
Issues in Technology
Transfer: Interactions
and Intellectual
Property
Chair — Kathleen Denis,
PhD, Rockefeller
University
This session will focus
on the interactions
among academic
researchers, their
technology transfer
office and industry
partners. An
introduction will
discuss the various
roles and
responsibilities of all
of the parties involved
and hope to begin to
demystify academic –
industry relations. The
basics of patents will
be presented with an
emphasis on what they
can and cannot
successfully cover, as
well as what a
researcher needs to do
to maximize the chances
of a positive outcome.
A variety of agreements
used in academic –
industry relationships
will be discussed in the
next talk, with an
emphasis on the
importance of creating a
good relationship
amongst all parties.
Finally, the session
will close with an
honest appraisal of the
good, the bad and the
ugly of new company
formation in the biotech
industry.
Session V.
Ask the Experts: Drug
Discovery for
Neurodegenerative
Disease
Chair — Todd Sherer,
PhD, Michael J. Fox
Foundation
This breakout session
will focus on
disease-specific issues
in drug discovery and
development. The
session will include 10
minute concurrent
presentations from
experts in Alzheimer’s
disease, Parkinson’s
disease, Huntington’s
disease, ALS, as well as
‘orphan’
neurodegenerative
diseases. A 50-minute
concurrent Q&A follows
the presentations,
allowing participants to
ask specific questions
pertaining to drug
discovery. The ultimate
aim of this session is
to inform participants
of specific issues
related to the drug
discovery process in
certain disease areas
(such as selection of
animal models, target
validation and
pre-clinical
development), to devise
potential solutions to
these problems and to
inform the funding
agencies of where
cross-cutting issues
should be addressed by
specific funding or
legislative initiatives.
Session VI.
Resources and Services
for Advancing Drug
Discovery
Chair — Lorenzo Refolo,
PhD, National Institutes
of Health/National
Institute of
Neurological Disorders
and Stroke
This session will focus
on descriptions of the
resources available
through a variety of
mechanisms within
academia, the National
Institutes of Health (NIH),
foundations and
commercial vendors.
Speakers will focus on
resources for assay
development, target
identification, drug
discovery, drug
development,
pre-clinical toxicology
evaluation and other
components needed for
the translation of
pre-clinical drug
candidates into
potential therapies
tested in clinical
trials. In particular,
it will include specific
descriptions of programs
available to academic
investigators through
individual NIH
Institutes, including
the National Institute
on Aging (NIA) and the
National Institute of
Neurological Disorders
and Stroke (NINDS), as
well as trans-NIH
programs including the
NIH Roadmap for
Medical Research and
the NIH Blueprint for
Neuroscience Research.
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