Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrigs Disease is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Motor neurons reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. The progressive degeneration of the motor neurons in ALS eventually leads to their death. When the motor neurons die, the ability of the brain to initiate and control muscle movement is lost. With voluntary muscle action progressively affected, patients in the later stages of the disease may become totally paralyzed. In January 2007, INSMED announced that the Italian Ministry of Health requested INSMED corporation to make Iplex available to treat Italian patients sufferings from ALS. IGF-1, the main component of Iplex, was the subject of a recent clinical trial in ALS. It involved 330 people with ALS from 20 ALS treatment centres across the United States. The drug was injected under the skin (subcutaneous delivery) in a randomized double-blinded placebo-controlled trial – this is the gold standard way of conducting a clinical trial. At the end of the two-year treatment period, there were no differences between people with ALS who received IGF-1 and those who received placebo in muscle strength, the need for a tracheostomy for breathing, or survival, indicating that IGF-1 provided patients no benefit. The current results are published in the November 25 issue of Neurology.
These neurotransmitters keep overactive motor neurons from firing and also play a role in the relaxation of muscles after contraction. When inhibitory neurons are unable to release their neurotransmitters, motor neurons fire out of control and muscles have difficulty relaxing. This causes the muscle spasms and spastic paralysis seen in tetanus infection.The tetanus toxin, tetanospasmin, is made up of a heavy chain and a light chain. There are three domains, each of which contributes to the pathophysiology of the toxin. The heavy chain has two of the domains. The N-terminal side of the heavy chain helps with membrane translocation, and the C-terminal side helps the toxin locate the specific receptor site on the correct neuron. The light chain domain cleaves the VAMP protein once it arrives in the inhibitory neuron cytosol.There are four main steps in tetanuss mechanism of action: binding to the neuron, internalization of the toxin, membrane translocation, and cleavage of the target VAMP. Neurospecific binding
The toxin travels from the wound site to the neuromuscular junction through the bloodstream where it binds to the presynaptic membrane of a motor neuron. The heavy chain C-terminal domain aids in the binding to the correct site, recognizing and binding to the correct glycoproteins and glycolipids in the presynaptic membrane. The toxin binds to a site that will be taken into the neuron as an endocytic vesicle that will travel down the axon, past the cell body, and down the dendrites to the dendritic terminal at the spine and central nervous system.