Abstract
Introduction
Nicotine has long been known to improve cognitive function, but its adverse
effects make it problematic as a treatment for diseases of cognitive
dysfunction. Recent research has revealed that certain subtypes of nicotinic
acetylcholinesterase receptors (nAChRs) in the brain are involved in cognitive
function. Agents that target these nAChRs have shown promise in Alzheimer' s
disease, attention-defi cit/hyperactivity disorder, schizophrenia, and mild
cognitive impairment. Research also suggests that these agents may not only
improve cognition but also be neuroprotective. Thus, hopes have been raised
that these agents may be disease-modifying therapeutics for neurodegenerative
diseases.
Get the Answers You Need to Shape Your Strategy
- Although the role of neural nicotinic receptors in cognition has been
known since the 1980s, development of nAChR subtype-specific agonists has
proven difficult. Why have previous agents failed during early stages of
development?
- Several small biopharmaceutical companies have subtype-specific nAChRs in
clinical development for diseases of cognitive dysfunction. The most advanced
of these agents are in Phase II. Which of these companies have agents in
Phase II trials, and which Big Pharma companies have partnered with them? When
might nAChR agents now in development reach the market?
- Several pharmaceutical companies are expected to enter candidate nAChR
agonists for the treatment of cognitive disorders into the clinic from their
in-house programs. Which Big Pharma company has already entered its
smoking-cessation drug into pilot trials for schizophrenia?
- One disease condition that is a target for nAChR agonists is mild
cognitive impairment (MCI), a less severe form of cognitive dysfunction than
Alzheimer' s disease. Some types of MCI may be precursors of Alzheimer' s.
What methods are researchers using to clarify which types of MCI have a
high risk of progression to AD?
Scope
- Prospective cognitive dysfunction disease targets for nicotinic
receptor agonists: Alzheimer' s disease, mild cognitive impairment,
age-associated memory impairment, schizophrenia,
attentiondeficit/hyperactivity disorder, Parkinson' s disease.
- Biology of nicotinic receptors: structure, function, and subtypes
of nAChRs; functional studies of nicotinic receptors being targeted in
cognition improvement; the role of the α7 nAChR in attention; studies of
the α7 nAChR in schizophrenia and Alzheimer' s disease.
- Subtype-specifi c nAChR agonists in clinical development for cognitive
disorders: profiles of the leading drug candidates in the nAChR agonist
programs of five leading biopharmaceutical companies.
- Outlook: growing corporate interest in nAChR agonists; the push
toward proof-of-concept in human clinical trials; lingering concerns about
addictive properties of particular subtype-specifi c nAChRs.
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