Neurodegenerative diseases administration

Melatonin secretion is synchronized to the light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) and low diurnal baseline levels (about 10 pg/ml plasma). Studies have supported the value of the exogenous administration of melatonin in circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders of the immune function, and oxidative damage (Karasek et al. 2002 Pandi-Perumal et al. 2005, 2006 Srinivasan et al. 2005a,b, 2006 Hardeland et al. 2006). 

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... 

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. 

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. 

Finally, the data reinforce the proposal (see Knoll, 2001, for review) that prophylactic administration of a synthetic mesencephalic enhancer substance during postdevelopmental life could significantly slow the unavoidable decay of behavioral performances, prolong life, and prevent or delay the onset of age-related neurodegenerative diseases, such as Parkinson s and Alzheimer s. 

A list of monitoring parameters is given in Table 57-8. It is important to educate patients and caregivers that IPD is a neurodegenerative disease that often progresses with time and that not all symptoms are amenable to treatment. They can participate in treatment by recording medication administration times as well as the duration of on and off times that can be reviewed at each office visit. If a bothersome symptom such as dystonia occurs only infrequently, it can be videotaped by the family to be reviewed with the physician. 

Oxidative stress is closely associated with the pathogenesis of ALS. Several antioxidants including vitamin E, acetylcysteine, methylcobalamin, and glutathione have been tested in clinical trials of ALS. Coenzyme QIO (CoQlO) is an antioxidant and mitochondrial cofactor (Fig. 9.12). It not only prevents lipid peroxidation but also stabilizes the Ca " channels. Its oral administration increases CoQlO levels in mitochondria. CoQlO produces promising effects in ALS transgenic mice and in clinical trials for neurodegenerative diseases other than ALS. Phase II clinical trial of CoQlO in ALS patients indicate that this dmg is ineffective in producing beneficial effects in ALS patients (Levy et al., 2006), and opinions on phase III trials have been controversial (Kaufmann et al., 2009). 

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