Module 35 Flashcards
What is the possible connection between myelin basic protein and multiple sclerosis? What treatment strategies are based on this possible connection?
- Multiple sclerosis (MS) is a demyelinating disease, and studies have found antibodies against myelin basic protein in the serum of patients with MS. It has the characteristics of an autoimmune disease. One hypothesis for the etiology of MS is a cross reactivity between herpes virus-6 and myelin basic protein.
One strategy to treat MS is to give glatiramer acetate, which is a random polymer of glutamic acid, lysine, alanine, and tyrosine, the four amino acids in myelin basic protein. This is based on the fact that large doses of an antigen can induce immune tolerance. Glatiramer acetate is somewhat effective in MS, but it certainly is not a cure.
What is the evidence to support the efficacy of Liberation Therapy for MS?
- Liberation therapy involved venoplasy or stenting of veins leading from the brain based on the hypothesis that MS is caused by venous insufficiency. The original studies by Zamboni were not controlled trials. Later studies found that apparent abnormalities in cerebral veins as determined by Doppler sonography were just as common in normal people as in patients with MS.
- Many desperate MS patients went to other countries to have the procedure done, and there were several adverse outcomes including death. It was an implausible hypothesis given what we know about the involvement of the immune system in the pathogenesis of MS.
What is the possible connection between microglia cells and Alzheimer’s disease? What prevention strategies are based on this possible connection?
- The pathogenesis of Alzheimer’s disease is not well understood. The major hypothesis is that amyloid deposits lead to inflammation and death of neurons.
○ Microglial cells are brain macrophages and are major mediators of inflammation in the brain.- It was noticed that patients taking dapsone for leprosy had a much lower incidence of Alzheimer’s disease, and dapsone inhibits several inflammatory pathways.
○ However, dapsone is associated with a wide range of side-effects and is not patentable.
○ There are no trials of dapsone for the treatment of Alzheimer’s disease, but the dapsone observations led to the hypothesis that other antiinflammatory drugs might prevent or treat Alzheimer’s disease. - There was some evidence that aspirin decreased the risk of Alzheimer’s disease, and it was hoped that the COX2 inhibiters would decrease the incidence of Alzheimer’s disease without the risk of bleeding associated with nonselective NSAIDs.
○ However, COX2 inhibiters turned out to increase the risk of cardiovascular events, and better studies did not find evidence that aspirin decreased the risk of Alzheimer’s disease.
-A recent hypothesis is that Alzheimer’s disease is caused by a reaction to a chronic infection to something like herpes. Amyloid protein is a very good antimicrobial agent and the production of amyloid may be a response to the infection. However, the amyloid can also lead to inflammation that causes brain damage.
- It was noticed that patients taking dapsone for leprosy had a much lower incidence of Alzheimer’s disease, and dapsone inhibits several inflammatory pathways.
What is the evidence that Ginkgo biloba is useful in the treatment of Alzheimer’s disease?
Although there were poorly designed studies that claimed to show that Ginkgo produced memory improvement in patients with dementia, subsequent studies failed to find a significant benefit
What neuropeptide/”hormone” may be related to “multiple chemical sensitivity syndrome”?
- Although no one can say that multiple chemical sensitivity syndrome does not exist, most of the practitioners, including physicians, who claim to benefit such patients use very questionable methods. A study done by an allergist in Toronto found a correlation between a gene associated with panic disorder and the risk of multiple chemical sensitivity syndrome. I would be willing to bet that in most cases the symptoms associated with the syndrome are caused by fear rather than chemicals, and the practitioners feed into this fear. This is quite similar to what I have seen with patients who believe that they are allergic to all drugs, and when tested, they have the same symptoms when treated with placebo.
There is epidemiologic evidence that smoking can have effects on the risk of specific CNS diseases. What are the diseases, and what is the apparent effect?
Smoking appears to increase the risk of Alzheimer’s disease, which is consistent with the evidence that other risk factors for cardiovascular disease are also risk factors for Alzheimer’s disease. In contrast, smoking appears to decrease the risk of Parkinson’s disease. This is a poor tradeoff when one considers all of the negative consequences of smoking.
