Amyotrophic lateral sclerosis treatment

In summary, the steadily increasing size of geriatric populations in developed countries and the resultant increases in age-related diseases of the brain have provided the impetus for intensive study of the processes underlying neurodegeneration. A better understanding of these processes will likely lead to better methods of treatment not only for progressive memory disorders such as Alzheimer disease, but also for motor disorders such as amyotrophic lateral sclerosis, and cerebrovascular disorders such as stroke. 

Ciliary neurotrophic factor (CNTF) decreases naturally occurring and axotomy-induced cell death and has been evaluated as a treatment for neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS)... 

Jiang YM, Yamamoto M, Kobayashi Y, Yoshihara T, Liang Y, Terao S, Takeuchi H, Ishigaki S, Katsuno M, Adachi H, Niwa J, Tanaka F, Doyu M, Yoshida M, Hashizume Y, Sobue G (2005) Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. Ann Neurol 57(2) 236-251 Johnstone RW (2002) Histone-deacetylase inhibitors novel dmgs for the treatment of cancer. Nat Rev Dmg Discov l(4) 287-299... 

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. 

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). 

Baclofen is a GABA agonist at GABA B receptors and it has a presynaptic inhibitory function by reducing calcium influx. Its indication is increased extensor tone and clonus. Intrathecal administration may control severe spasticity pain. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis and amyotrophic lateral sclerosis. Its central nervous system effects include drowsiness, somnolence and seizure activity in epileptic patients. 

Besides AD, memantine has been used for the treatment of stroke, Parkinson disease, amyotrophic lateral sclerosis, epilepsy, HIV associated dementia,... 

Polyaromatic amine derivatives, (III) and (IV), prepared by Tai (5) and Mueller (6), respectively, designed as NMDA selective receptor channel blockers to protect neuronal cell receptors from excitotoxic cell death were used in the treatment of Alzheimer s and Huntington s disease and amyotrophic lateral sclerosis. 

McGeer, E.G., McGeer, P.L. (2005). Pharmacologic approaches to the treatment of amyotrophic lateral sclerosis. BioDrugs 19 31-7. 

ALS CNTF Treatment Study Group (1996) A double blind placebo controlled clinical trial of subcutaneous recombinant human ciliary neuroti ophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neru ology 46(5) 1244—1249. 

Orrell RW, Lane RJM, Ross M (2005) Andoxidant treatment for amyotrophic lateral sclerosis/motor neuron disease. The Cochrane Database for Systemadc Reviews, Volume 4, The Cochrane Col-labor adon. 

Bushara KO (1997) Sialorrhea in amyotrophic lateral sclerosis A hypothesis of a new treatment—botulinum toxin A injections of the parotid glands. Med Hypotheses 48 337-339. 

Desnuelle C, Dib M, Garrel C, Eavier A (2001) ALS Riluzole-Tocopherol Study Group. A double blind, placebo controlled randomized clinical trial of alpha tocopherol in the treatment of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord 2(1) 9-18. 

Lange DJ, Murphy PL, Diamond B, Appel V, Lai EC, Younger DS, Appel SH (1998) Selegiline is ineffective in a collaborative double-blind, placebo-controlled trial for treatment of amyotrophic lateral sclerosis. Arch Neurol 55(l) 93-96. 

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