Neurological disorders are among the most devastating of illnesses. Many subjects with neurological disorders experience both, a deterioration in their quality of life and an increased mortality from their disease. For example, subjects with multiple sclerosis and Huntington's disease are often affected in their young adult years and experience many years of decreased productivity.

At this point, neurological disease cannot be cured. While great strides have been made in defining the abnormal genes and proteins behind many diseases, most therapies aim at decreasing the severity of symptoms and preventing exacerbations such as in diseases with recurrent attacks including migraines, epilepsy and multiple sclerosis.

This Update includes all disorders related to the separate components of the nervous system: the brain, the spinal cord and peripheral nervous system. The prevalence of some of the more common neurological disorders is as follows:

Condition	Prevalence
Migraine	11-18 million people
Alzheimer's Disease	4 million people
Epilepsy	2 million people
Parkinson's Disease	1.5 million people
Multiple Sclerosis	350,000 people
Huntington's Disease	250,000 people
Amyotrophic Lateral Sclerosis	30,000 people

Migraine is very common and afflicts primarily women; it is estimated that 15% of women and 6% of men have recurrent migraine attacks. Both serotonin and dopamine receptors seem activated in migraine; serotonin receptor agonists (for example, triptans) and dopamine receptor antagonists (for example, metoclopramide) are therapeutically effective in migraine attacks.

There are more than 20 drugs undergoing clinical trials for the treatment or prevention of migraine attacks at this time. About half of the trials are for triptan-type agents (serotonin-receptor agonists). The rest include dopamine receptor antagonists, non-steroidal agents, and anti-epileptic drugs. Two drugs were approved in 2001 for the treatment of migraine. These were frovatriptan (Frova) (Vernalis) and almotriptan (Axert) (Pharmacia); the trial results indicate that Axert has similar efficacy to Imitrex tablets (sumatriptan) (GlaxoSmithKline), a current leading anti-migraine medication. Research has also shown that Axert is less likely to cause chest pain as a side effect compared to sumatriptan.

Alzheimer's Disease (AD) is a progressive, degenerative disorder of the brain and the most common form of dementia. In a 1993 national survey, about 19 million Americans said that they have a family member who suffers from AD. There will be about 14 million people with AD by the middle of this century unless a cure or prevention is found for this disease. To understand the enormity of this disorder, it is important to realize that one in 10 people over age 65 and nearly half of those over 85 have AD.

Most of the drugs currently in development for AD act on preventing the action of the cholinesterase enzymes. Blocking this enzyme increases the level of acetylcholine in the brain and improves the neurological functioning of subjects with dementia. There are more than 30 drugs undergoing clinical trials at present for AD. Two drugs have recently been approved for the treatment of Alzheimer's Disease by the FDA; these were Exelon (Rivastigmine tartarate by Forrest Laboratories) and Reminyl (Galantamine by Jansen Research Foundation). Reminyl (galantamine) is a nicotinic modulator that is being developed for the treatment of both chronic fatigue syndrome and AD. This drug works by slowing down or inhibiting acetylcholinesterase, which is the enzyme responsible for degrading the neurotransmitter acetylcholine. Study results show that volunteers with Alzheimer's treated with Reminyl exhibited improved memory, behavior, and ability to perform activities of daily living. In addition, a second study suggested that the cognitive and functional benefits of galantamine might be sustained for at least a year.

Epilepsy afflicts about two million persons in America. Although few people die because of their seizures, they experience frequent enough attacks that it affects their quality of life. Medications to control seizures are fully effective in only about half of people with epilepsy. The rest end up taking combinations of drugs, or even surgery, to control their epilepsy.

There are currently about 15 drugs in clinical trials for the treatment of epilepsy. Many of these drugs act as anti-epileptics by increasing the level of Gamma-amino butyric acid (GABA) or by stimulating GABA receptors. GABA is an inhibitory molecule. Activating GABA-related foci in the brain raises the threshold at which excitatory neurons fire and decreases the chance of seizures.

Parkinson's Disease afflicts 1.5 million people in America. Not only is the quality of life diminished for many persons with Parkinson's but there is also a significant chance of developing dementia. There are currently more than 30 drugs/drug-systems in development for the management of Parkinson's Disease. Many of these drugs function as dopamine agonists. Since adults with Parkinson's Disease develop loss of the dopamine-producing neurons in the brain, it is thought that the use of dopamine agonists could reduce some of the movement disorders experienced by people with this disorder.

Some of these dopamine agonists in phase III clinical trials include Sumanirole, Apomorphine, Modafinil, and Rotigotine (Aderis Pharmaceuticals). Apomorphine has been approved in the United Kingdom for use in subjects with Parkinsonism who experience on-off fluctuations in late stage disease. Other phase III trials include the measurement of dopamine transporters in the midbrain with use of a radioactive molecule that binds specifically to these proteins. Altropane was shown, through SPECT imaging, to have the ability to distinguish subjects having the clinical syndrome of Parkinsonism whose symptoms are not caused by neuropathology in the dopamine producing cells in the basal ganglia and the extrapyramidal foci in the brain from patients with typical Parkinson's Disease. The distinction is important since the treatment and prognosis of the two groups of patients differs.

In summary, many of the drugs in the pipeline for serious neurological conditions may help in controlling their symptoms. However, new advances in neurology will come when further research uncovers the etiology of neuronal destruction in diseases such as Alzheimer's, Parkinson's and Amyotrophic Lateral Sclerosis. Drugs that can halt the process of neuronal death or stimulate neuronal health will ultimately have the most powerful effect helping patients reverse some of the debilitating symptoms of neurodegenerative conditions.