Nicotinic Receptor Agonists for Treating Diseases of Cognitive Dysfunction
Decision Resources
November 13, 2007 20 Pages - SKU: DECR1762170
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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-specifi c agonists has proven diffi cult. Why have previous agents failed during early stages
of development?
- Several small biopharmaceutical companies have subtype-specifi c 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, attentiondefi
cit/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 á7 nAChR in attention;
studies of the á7 nAChR in schizophrenia and Alzheimer's disease.
- Subtype-specifi c nAChR agonists in clinical development for cognitive disorders: profi les
of the leading drug candidates in the nAChR agonist programs of fi ve 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.
Please note, the PDF e-mail from publisher version of this report is for a global site license.
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- Executive Summary
- Strategic Considerations
- Stakeholder Implications
- Introduction
- Diseases Involving Cognitive Dysfunction That Are Prospective Targets for Nicotinic
- Receptor Agonists
- Alzheimer’s Disease
- Mild Cognitive Impairment
- Age-Associated Memory Impairment
- Schizophrenia
- Attention-Defi cit/Hyperactivity Disorder
- Parkinson’s Disease
- Biology of Nicotinic Receptors
- Functional Studies of Nicotinic Receptors That Are Targets in Improvement of Cognition
- Functional Studies of nAChRs Containing the â4 Subunit Using a Subtype-Specifi c Drug
- Functional Studies of nAChRs Containing the â2 Subunit Using Genetic Manipulation
- A Study of the Role of the á7 nAChR in Attention
- Other Studies of the Potential Role of á7 Receptors in Schizophrenia and Alzheimer’s
- Disease
- Subtype-Specifi c nAChR Agonists in Clinical Development for Cognitive Disorders
- Targacept/AstraZeneca’s TC-1734/AZD-3480
- CoMentis’s GTS-21
- Memory Pharmaceuticals/Roche’s MEM-3454
- EnVivo Pharmaceuticals’ á7 Agonist Program
- NeuroSearch/Abbott’s Nicotinic Receptor Agonist Program
- Outlook
- Tables:
- 1. Prevalence in the Major Markets of Diseases Involving Cognitive Dysfunction That Are Targets for Nicotinic Acetylcholine Receptor Agonists, 2006
- 2. Properties of Neural Nicotinic Receptor Subtypes That Are Targets in Cognition
- 3. Select Subtype-Specifi c Nicotinic Receptor Agonists in Development for Cognitive Disorders
- Figures:
- 1. Cognition and Memory
- 2. Dopamine Pathways
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