Uncoupling Neuroprotection from Immunosuppression: the Discovery of ILS-920 - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 316

CHAPTER 14
Uncoupling Neuroprotection
from Immunosuppression: the
Discovery of ILS-920
EDMUND I. GRAZIANI
Worldwide Medicinal Chemistry, Pfizer Global Research & Development,
455 Eastern Point Road, Groton, CT 06340, USA
14.1 Introduction
Ischemic stroke—injury due to an obstruction within a blood vessel that
restricts blood supply to the brain—is the leading cause of neurological dis-
ability worldwide and the most common cause of adult long-term disability in
the United States. 1 Existing approved therapies to treat ischemic stroke are
limited to recombinant tissue plasminogen activator (rt-PA), which acts as a
thrombolytic that targets the underlying vessel blockage without addressing
stroke-induced neurological deficits. Moreover, rt-PA must be administered
within the first six hours following an ischemic event. Since rt-PA also increases
the likelihood of hemorrhagic stroke, a CT scan is required prior to adminis-
tration to rule out intracranial bleeding. Thus, only 5% of stroke patients ever
receive rt-PA treatment. 1
There are no marketed neuroprotective agents for ischemic stroke, despite
decades of clinical trials. The recent and highly publicized Phase 3 failure of
NXY-059, a novel free-radical scavenger neuroprotectant, hastened the call for
an end to neuroprotective therapy research for treating stroke. 2 Nonethe-
less, the Stroke Therapy Academic Industry Roundtable (STAIR) has recently