Neurodegenerative diseases treatment

Bayer [199-203] has claimed in a series of patents a number of aryl sulfonyl esters as cannabinoid agonists for the treatment and prophylaxis of neurodegenerative diseases. Following on from this a number of publications detailing the in vitro and in vivo profiles on two of these compounds, BAY 38-7271 (317) and BAY 59-3074 (318), have been published. 

Growth factor administration may also be a useful treatment for neurodegenerative diseases, such as Alzheimer s disease or Parkinson s disease, which are characterized by the degeneration of neuronal cell populations. It was found that the NGF promoted nerve regeneration within conduits at an early stage, but the effect did not last after one month. This was attributed to the rapid decline in NGF concentrations in the conduit due to degradation in aqueous media and leakage from the... 

IGF-I is widely expressed in the central nervous system. IGF-II is also present, being produced mainly by tissues at vascular interfaces with the brain. Both growth factors, along with insulin, play a number of important roles in the nervous system. They stimulate the growth and development of various neuronal populations and promote neurotrophic effects (discussed later) and may, therefore, be of potential use in the treatment of various neurodegenerative diseases. 

Each neurotrophic factor influences the growth and development of a specific group of neuronal types, with some cells being sensitive to several such factors. Many sustain specific neuronal populations whose death underlines various neurodegenerative diseases. This raises the possibility that these regulatory molecules may be of benefit in treating such diseases. Results from early clinical trials have been at best mixed, but many remain optimistic that neurotrophic factors may provide future effective treatments for some currently incurable neurodegenerative conditions. 

The recent approval of the SNRI duloxetine for the treatment of diabetic neuropathy reinforces the utility of this drug class in the treatment of neuropathic pain. Other largely untapped areas which remain to be exploited with this drug class include sexual dysfunction, such as premature ejaculation, irritable bowel syndrome, obesity, neurodegenerative diseases such as Parkinson s disease, restless leg syndrome, and substance abuse and addiction. It is apparent that considerable opportunities for drug discovery will exist in this area for some time to come. 

Two neurodegenerative diseases will be considered in greater detail here, Alzheimer s disease and Parkinson s disease, due to the pertinence of herbal medications to their treatment. Also discussed in some detail are vascular dementia and normal aging. Other degenerative conditions may benefit from herbal medications, but have not received the amount of attention in research that the above conditions have. Of particular interest to many degenerative conditions are herbal medications with demonstrated antioxidant and neuroprotective effects. 

Dore S, Kar S, Quirion R. 1997. Rediscovering an old friend, IGF-I potential use in the treatment of neurodegenerative diseases. Trends Neurosci 20 326-331. 

Neurodegenerative diseases are generally characterized by the death of specific neuronal populations. Many such neurons are responsive, in vitro at least, to one or more neurotrophic factor. This infers a potential therapeutic role for these molecules in the treatment of such conditions (Table 7.11). Lack of current effective therapies for the treatment of any neurodegenerative disease renders this avenue of investigation even more attractive. Target diseases include amyotrophic lateral sclerosis and peripheral neuropathies, as well as various neurodegenerative diseases of the brain, including Alzheimer s and Parkinson s. 

The use of a combination of neurotrophic factors in the treatment of neurodegenerative disease may well prove an avenue worthy of consideration. For example, pre-clinical studies reveal that administration of a combination of CNTF and BDNF to Wobbler mice (an animal model of motor neuron disease), prevented progression of motor neuron dysfuction, whereas administration of either factor on its own only slowed progression of the disease. 

Limited clinical success keeps optimism alive that neurotrophic factors will find application in the treatment of some neurodegenerative disease. However, no member of this family of regulatory proteins have been approved for medical use, despite all the clinical investigations undertaken over the last decade and a half... 

Parkinson s disease together with Alzheimer s disease, multiple sclerosis, Huntington s disease, and amyotrophic lateral sclerosis belongs to a group of neurodegenerative diseases for which the pharmacological treatments are mostly symptomatic. 

Amyotrophic lateral sclerosis (ALS) is a progressive, usually fatal, neurodegenerative disease caused by the degeneration of motor neurons in the central nervous system. No cure has yet been found for ALS. The U.S. Food and Drug Administration (FDA) has approved riluzole as the first drug treatment for the disease. It delays the onset of ventilator-dependence or tracheostomy in selected patients. A Cochrane review states a 9% gain in the probability of surviving one year (see Miller et ah, 2007). 

Because melatonin is sold over the counter and its production is not the subject of strict regulation as is that of prescribed medications, it is in wide use, but insufficient scientifically controlled information is available. Another consequence of the popularity and availability of the hormone is its use in a wide array of situations in which its efficacy has not been proven yet for instance, as treatment for neurodegenerative diseases or as a sleep-inducing medication. It also has been tried as an antidepressant, but that effect is still unclear. The administration of melatonin to patients with bipolar depression, especially to rapid cyclers, is of interest, especially if its use is associated with the presumed decrease in nocturnal hormonal levels and increase in sensitivity to light (Lewy et al. 1985). The possibility that melatonin also serves as a stabilizer of rhythm in these patients is in accord with the homeostatic effect of several other hormones that have been previously discussed here. 

Edited by Caine D. Philadelphia, PA, WB Saunders, 1994, pp 177-194 Hefti E, Hartikka J, Knusel B Eunction of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases. Neurobiol Aging 10 515-533, 1989... 

Hornig-Rohan M, Amsterdam JD Clinical and biological correlates of treatment-resistant depression an overview. J Clin Psychiatry 24 220-227, 1994 Horowski R, Wachtel L, Turski L, et al Glutamate excitotoxicity as a possible pathogenetic mechanism in chronic neurodegeneration, in Neurodegenerative Diseases. Edited by Caine DB. Philadelphia, PA, WB Saunders, 1994, pp 163-174... 

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