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Ion Channels as Therapeutic Targets for Multiple Diseases


Description: Ion channels play an important role in numerous cell types and occur as large families of related genes with cell-specific expression patterns. Considering the publication of the human genome and the progress in transcription profiling revealing the tissue specific distributions of ion channels, they will play a much more important role as therapeutic drug targets in the future. These advancements combined with cell-based assays providing biologically relevant information to genomic and proteomic information will make ion channels a favorable class of selective, tissue specific, drug targets. Currently, there are active pharmaceutical research and development programs involving ion channels in a number of areas, including asthma, inflammation, arrhythmia and CNS disorders Several disease states are related to dysfunctional ion channels. Among prominent groups are cardiac arrhythmias, diabetes, hypertension, angina pectoris and epilepsy. Several drugs already marketed have generated substantial revenues for the companies. Already today, drugs targeting ion channels generates over 6 billion dollars in sales per annum. According to the FDA, the number of new approved drugs targeting ion channels is equal to or even higher than that for drugs targeting proteases, polymerases and reverse transcriptases. But, inspite of their remarkable physiological value, ion channels have stayed a relatively unexploited therapeutic target class, especially in comparison to target areas such as G-protein coupled receptors or kinases. Major challenges for high throughput screening (HTS) with high information content have been the main limiting factor for an explosion in R&D. BioSeeker Group AB has recognized the interest and need for a continuous surveillance within the field of ion channels as targets for drug discovery. This report includes market outlooks and updated information on ion channel targets related to diseases such as urinary incontinence, multiple sclerosis, diabetes, inflammation, pain and CNS disorders such as epilepsy and depression. Scientific advancements are presented in relation to each disease group. Further, the report comments on new ion channel drug discovery technologies. Technological breakthroughs have been made for drug discovery tools applied in the hunt for novel therapeutics targeting ion channels. BioSeeker Group has in identified improvements for new drug discovery platforms that have the potential for substantially improve HTS. According to a distinguished scientist and product developers, technologies will have to change to collect more data on each individual experiment and a need for more human settings is also clear. Technologies such as molecular targeting imaging with local electrical data and 3D-anatomical pictures will probably be tools frequently used in the future. The report also includes a coverage of the conference Ion Channels in drug discovery and development held 24-25 October this year. Key alliances and company activities are also described Apart from the pharma industry itself, this report is of value to investors, science incubators, investigators, contract research organizations or any other types of organization that have an interest in new antifungal therapies. Companies Included in this Report Abbott Laboratories, Amersham BioSciences, Asta Medica, AstraZeneca, Aurora BioSciences, Aviva Biosciences, Axon Instruments, Axxam s.r.l, Bayer, Caliper Technologies, Cellectricon AB, CeNeS Pharmaceuticals, Elan Pharmaceuticals, Essen Instruments, Evotec/Genion, Icagen Inc, Merck, Molecular Devices/Cytion, Nanion Technologies, Neuromed Technologies Inc, Neurosearch, Nimbus Biotechnology, Novartis, Parion Sciences, RW Johnson Pharmaceutical Research Institute, Schering-Plough, Sophion Bioscience, Wyeth Corp, Xention Discovery.


Contents:

EXECUTIVE SUMMARY

8

METHODOLOGY

10

INTRODUCTION

11

SHORT MARKET OUTLOOKS

13

Autoimmune and Inflammatory Diseases

13

Multiple Sclerosis

13

Inflammatory Bowel Disease

14

Rheumatoid Arthritis

14

Psoriasis

14

Dermatitis

15

Asthma

15

Metabolic And Endocrinological Diseases

16

Companies with Clinical Stage Projects for Obesity

17

Diabetes

17

Starlix (Nateglinide)

18

Obesity

19

Cancer

20

Neurological Diseases

21

Selected Drugs

21

Nimotip (Nimotide)

21

Ziconotide

22

Sonata (Zaleplon)

22

Topamax (Topiramate)

24

Osteoporosis

25

TARGETS FOR DRUG DISCOVERY

26

Using Ion Channels to Improve Antimicrobials

26

Potassium Channel Inhibitors for Immunotherapy

27

Diabetes

28

New Compounds Inhibiting the Kv1.3 Potassium Channel for the use as immunosupressprs

30

Allergy and Asthma

31

Using Sodium Channel Inhibitors for the Treatment of Chronic Bronchitis

31

Hunting for New CNS Disorder Targets

32

Epilepsy

33

Migraine

35

Stroke

35

Urinary Incontinence

36

Intracellular Chloride Channels and Cancer

36

New Target for Treating ALzheimer's Disease

37

Calcium Channels

38

Hypertension

38

Chronic Pain Reliever Without Side Effects

38

New Company Created

39

Ion Channel Found With Possible Application for Treatment of Anxiety Disorders

41

ION CHANNEL DRUG DISCOVERY TECHNOLOGIES

42

Direct Assays

43

Indirect Assays

45

What Can Be Measured?

47

Market Possibilities

49

Ion Channels as Therapeutic Targets

49

The Future of Cell-based Assays

53

NEW TECHNOLOGIES SPEED ION CHANNEL DRUG DISCOVERY

58

Embarassement of Richness

58

Will People be the Limiting Factor?

58

Cardiac Arrythmia

61

Strategy for Testing QT Prolongation

62

Poentiometric Dye Cel Based Assay

63

Breakthroughs in Patch-on-a-Chip HTS?

63

Cardiac Repolarization: Evaluation of an Rb+ Flux Assay in Comparison to Other Technologies

66

High-Throughput Electrophysiology in New Cell-Free Assay Formats

68

Parallell Oocyte Electrophyisiological Test Station (POET)

70

CONCLUSIONS

72

DISCLAIMER

73

INDEX

74




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