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市場調查報告書
針對認知功能障礙治療的尼古丁受體促效劑
Nicotinic Receptor Agonists for Treating Diseases of Cognitive Dysfunction
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本報告已在2011年12月21日停止出版。
針對認知功能障礙治療的尼古丁受體促效劑
本報告書內容包括：為尼古丁受體促效劑治療標的的認知功能障礙概要、尼古丁受體生物學、未來預測等。內容綱要摘記如下：
實施概要
介紹
為尼古丁受體促效劑治療標的的認知功能障礙相關疾病
- 阿茲海默症
- 輕度認知障礙
- 老年痴呆症
- 精神分裂症
- 注意力不足過動症（ADHD）
- 帕金森氏症
尼古丁受體的生物學
- 以改善認知為治療標的的尼古丁受體的功能性研究
- 包括利用次類型藥物之 Beta4 subunit 的 nAChRs 功能性研究
- 包括利用基因操作之 Beta4 subunit 的 AChRs 功能性研究
- α7nAChR 的角色研究
- 針對精神分裂症及阿茲海默症的 α7 受體角色研究
認知障礙臨床研究中的次類型nAChR促效藥
- Targacept/AstraZeneca 的 TC-1734/AZD-3480
- CoMentis 的 GTS-21
- Memory Pharmaceuticals/Roche 的 MEM-3454
- NeuroSearch/Abbott 的尼古丁受體促效劑計畫
未來發展預測
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.
Table of Contents
- 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 β4 Subunit Using a
Subtype-Specific Drug
- Functional Studies of nAChRs Containing the β2 Subunit Using
Genetic Manipulation
- A Study of the Role of the α7 nAChR in Attention
- Other Studies of the Potential Role of α7 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' α7 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-Specific Nicotinic Receptor Agonists in Development for
Cognitive Disorders
Figures:
- 1. Cognition and Memory
- 2. Dopamine Pathways
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