Neurodegenerative Diseases

Summary

Neurodegenerative diseases are drawing immense interest from the pharmaceutical industry and have inspired heavy competition in the race to introduce the next generation of improved drugs. Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis are analyzed in this report, which:

• Reviews their symptoms and pathology, presumed causes, methods of diagnosis, epidemiology
• Examines existing drug therapies for each disorder
• Surveys the R&D picture for each disease
• Tabulates the approximately 150 compounds in clinical development
• Discusses particularly noteworthy drug candidates.

Neurodegenerative diseases are caused by the loss or dysfunction of neurons in the brain or spinal cord. These diseases are especially devastating because the affected cells typically cannot regenerate following damage or death. Neurodegenerative Diseases: Next-Generation Drugs for Four Major Disorders deals with chronic neurodegenerative diseases by focusing on four of the most comprehensively studied such conditions: Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS).

To the pharmaceutical industry, perhaps the most important defining characteristic of these four diseases is the inadequacy of the standard of care. Existing treatments tend to address symptoms as opposed to modify disease course. Several relatively new drugs are available for AD, but they have only modest effects. There is a larger formulary on hand for PD, but treatments are plagued by the issues of side effects and diminishing returns. The landscape is even bleaker for HD and ALS, with only a single, moderately effective drug for each of these conditions. We examine the existing drug therapies for each of these diseases, grouping and discussing treatments according to their mechanism of action.

AD and PD present huge potential markets, with 5 million and 1 million US patients, respectively. HD and ALS are uncommon in comparison, with only about 30,000 US patients apiece, but all four diseases disproportionately affect the elderly, who comprise a steadily increasing share of the population in the developed world. Without an outright cure, most therapies would likely require long-term administration. These factors suggest that a company which can deliver an improved compound for one of these neurodegenerative disorders will earn a rich return on its investment.

Developing effective drugs for these diseases continues to be challenging. AD research has been stung by the recent setbacks of several novel compounds in Phase III trials. PD is an active field, but the greatest progress has been with next-generation versions of drugs that are already available. In HD and ALS, the late-stage clinical candidates are most often non-specific drugs that were originally developed for other indications.

Neurodegenerative Diseases: Next-Generation Drugs for Four Major Disorders surveys the investigational drugs in the pipeline for AD, PD, HD, and ALS. We list clinical-stage compounds, providing details about noteworthy candidates, and examine additional preclinical and research programs. The efforts of more than 115 companies working to develop treatments for these disorders are described.

Contents

• Chapter 1
• Introduction and Review of The Neurodegenerative Diseases: Pathology, Causes, Diagnosis, and Epidemiology
  • 1.1. Report Focus: Alzheimer's Disease, Parkinson's Disease, Huntington's Disease, Amyotrophic Lateral Sclerosis
  • 1.2. Report Organization
  • 1.3. Alzheimer's Disease
  • Pathology of Alzheimer's Disease
  • Causes of Alzheimer's Disease
  • Diagnosis of Alzheimer's Disease
  • Epidemiology of Alzheimer's Disease
  • 1.4. Parkinson's Disease
  • Pathology of Parkinson's Disease
  • Causes of Parkinson's Disease
  • Diagnosis of Parkinson's Disease
  • Epidemiology of Parkinson's Disease
  • 1.5. Huntington's Disease
  • Pathology of Huntington's Disease.
  • Causes of Huntington's Disease
  • Diagnosis of Huntington's Disease
  • Epidemiology of Huntington's Disease
  • 1.6. Amyotrophic Lateral Sclerosis
  • Pathology of Amyotrophic Lateral Sclerosis
  • Causes of Amyotrophic Lateral Sclerosis
  • Diagnosis of Amyotrophic Lateral Sclerosis
  • Epidemiology of Amyotrophic Lateral Sclerosis
• Chapter 2
• Current Pharmacologic Treatment Options
  • 2.1. Alzheimer's Disease
  • Cholinesterase Inhibitors
  • Aricept (Donepezil Hcl)
  • Exelon (Rivastigmine Tartrate)
  • Razadyne (Galantamine Hbr
  • Nmda Receptor Antagonists
  • Namenda (Memantine Hcl)
  • Other Treatments
  • 2.2. Parkinson's Disease
  • Levodopa
  • Dopamine Agonists
  • Mirapex (Pramipexole Dihcl
  • Requip (Ropinirole Hcl)
  • Neupro (Rotigotine)
  • Apokyn (Apomorphine)
  • Trivastal (Piribedil)
  • Comt Inhibitors
  • Tasmar (Tolcapone)
  • Comtan (Entacapone)
  • Mao Inhibitors
  • Selegiline
  • Azilect (Rasagiline)
  • Other Treatments for Motor Symptoms
  • Anticholinergics
  • Amantadine
  • Treatments for Non-Motor Symptoms
  • 2.3. Huntington's Disease
  • Dopamine Depletors
  • Xenazine (Tetrabenazine)
  • Other Treatments
  • 2.4. Amyotrophic Lateral Sclerosis
  • Glutamate Antagonists
  • Rilutek (Riluzole)
  • Other Treatments
• Chapter 3
• Compounds in Development: The next Generation of Drugs for Neurodegenerative Diseases
  • 3.1. Alzheimer's Disease
  • Cholinergic Dysfunction
  • Neuro-Hitech/Xel Pharmaceuticals
  • Debiopharm
  • Memory Pharmaceuticals/Roche
  • Astrazeneca/Targacept
  • Abbott Laboratories
  • Envivo Pharmaceuticals
  • Comentis
  • Torreypines Therapeutics
  • Merck & Co.
  • Anavex Life Sciences
  • Medivation/Pfizer
  • Glutamatergic Dysfunction
  • Forest Laboratories/Merz Pharma
  • Evotec
  • Cortex Pharmaceuticals
  • Lexicon Pharmaceuticals
  • Addex Pharmaceuticals
  • Serotonergic Dysfunction
  • Epix Pharmaceuticals/Glaxosmithkline
  • Suven Life Sciences
  • Memory Pharmaceuticals
  • Histaminergic Dysfunction
  • Amyloid Cascade: Inhibiting Production
  • Eli Lilly
  • Humanetics/Mount Sinai School of Medicine
  • Exonhit Therapeutics
  • Eisai
  • Comentis/Astellas Pharma
  • Noscira
  • Jado Technologies
  • Remegenix
  • Medisyn Technologies
  • Neurobiological Technologies
  • Galapagos
  • Others
  • Amyloid Cascade: Stimulating Removal
  • Elan/Wyeth
  • Eli Lilly
  • Novartis Pharma/Cytos Biotechnology
  • Merck & Co./Acumen Pharmaceuticals
  • Intellect Neurosciences
  • Others
  • Pfizer/Transtech Pharma
  • Amyloid Cascade: Preventing Aggregation
  • Bellus Health
  • Prana Biotechnology
  • Adeona Pharmaceuticals
  • Elan/Transition Therapeutics
  • Proteotech
  • Archer Pharmaceuticals
  • D-Pharm
  • Probiodrug
  • Neuro-Hitech
  • Pharmathene
  • Nymox Pharmaceutical
  • Ac Immune
  • Tau Pathology
  • Taurx Pharmaceuticals
  • Allon Therapeutics
  • Noscira
  • Oligomerix
  • Neuroprotection
  • Newron Pharmaceuticals
  • Intellect Neurosciences
  • Panacea Pharmaceuticals
  • Neurorestoration
  • Ceregene
  • Nsgene
  • Enkam Pharmaceuticals
  • Cholesterol and Energy Homeostasis
  • Glaxosmithkline
  • Accera
  • Resverlogix
  • Second Messenger Modulation
  • Helicon Therapeutics
  • Memory Pharmaceuticals
  • Decode Genetics
  • Sanofi-Aventis
  • 3.2. Parkinson's Disease
  • Dopaminergic Dysfunction
  • Vernalis
  • Spherics
  • Xenoport
  • Neuroderm
  • Amarin
  • Depomed
  • Axxonis Pharma
  • Solvay Pharmaceuticals
  • Neurogen
  • Neurosearch
  • Nupathe
  • Newron Pharmaceuticals/Merck Serono
  • Synosia Therapeutics
  • Paion
  • Targacept/Glaxosmithkline
  • Intra-Cellular Therapies
  • Adenosine A2a Receptor Modulation
  • Adenosite A2a Receptor Modulation
  • Biogen Idec/Vernalis
  • Schering-Plough
  • Synosia Therapeutics
  • Others
  • Glutamatergic and Noradrenergic Dysfunction
  • Faust Pharmaceuticals
  • Addex Pharmaceuticals/Merck & Co.
  • Neurim Pharmaceuticals
  • Vistagen Therapeutics
  • Santhera Pharmaceuticals/Juvantia Pharma
  • Alpha-Synuclein Pathology
  • Taurx Pharmaceuticals
  • Foldrx Pharmaceuticals
  • Proteotech
  • Bioarctic Neuroscience
  • Rentschler Biotechnologie
  • Prana Biotechnology
  • Panacea Pharmaceuticals
  • Alnylam Pharmaceuticals
  • Neuroprotection
  • Aeolus Pharmaceuticals
  • Vasogen
  • Trophos
  • Zenobia Therapeutics
  • Neurorestoration
  • Neurologix
  • Ceregene/Genzyme
  • Oxford Biomedica
  • Amsterdam Molecular Therapeutics
  • Neuronova
  • Nsgene
  • Armagen Technologies
  • Sangamo Biosciences
  • 3.3. Huntington's Disease
  • Dopamine Overactivity
  • Neurosearch
  • Glutamatergic Dysfunction
  • Cortex Pharmaceuticals
  • Vistagen
  • Huntingtin Pathology: Genetic Therapy
  • Isis Pharmaceuticals
  • Targeted Genetics
  • Alnylam Pharmaceuticals/Medtronic
  • Huntingtin Pathology: Preventing Aggregation
  • Raptor Pharmaceuticals
  • Repligen
  • Prana Biotechnology
  • Adeona Pharmaceuticals
  • Vertex Pharmaceuticals
  • Neuroprotection
  • Amarin
  • Intellect Neurosciences
  • Trophos
  • Neurologix
  • Keyneurotek Pharmaceuticals
  • Neurorestoration
  • Ceregene
  • Enkam Pharmaceuticals
  • Neurobiological Technologies
  • 3.4. Amyotrophic Lateral Sclerosis
  • Glutamatergic Dysfunction
  • Teva Pharmaceutical Industries
  • Faust Pharmaceuticals
  • Sod1 Pathology
  • Cytrx
  • Rxi Pharmaceuticals
  • Isis Pharmaceuticals
  • Amorfix Life Sciences/Biogen Idec
  • Neuroprotection
  • Aeolus Pharmaceuticals
  • Trophos
  • Maas Biolab
  • Trophic Factors
  • Sangamo Biosciences
  • Neuronova
  • Oxford Biomedica
  • Ceregene
  • Genzyme/Nsgene
  • Insmed
  • Sygnis Pharma
  • Microtubule Stabilization
  • Kinemed
• Chapter 4
• Conclusions and Outlook
  • References
  • Company Index with Web Addresses
• Tables and Figures
  • Figure 1.1. Amyloid Cascade Mechanism
  • Figure 2.1. Treatment Algorithm for Mild-to-Moderate Alzheimer's Disease
  • Figure 2.2. Treatment Algorithm for Moderate-to-Severe Alzheimer's Disease
  • Figure 2.3. Treatment Algorithm for Severe Alzheimer's Disease
  • Figure 2.4. Treatment Algorithm for Parkinson's Disease
  • Table 1.1. Ninds Diagnostic Criteria for Parkinson's Disease
  • Table 1.2. Revised El Escorial World Federation of Neurology Criteria for Als
  • Table 3.1. Drugs in Clinical Trials for Alzheimer's Disease
  • Table 3.2. Drugs in Clinical Trials for Parkinson's Disease
  • Table 3.3. Drugs in Clinical Trials for Huntington's Disease
  • Table 3.4. Drugs in Clinical Trials for Amyotrophic Lateral Sclerosis