January 9, 2010 at 2:12pm
Let's try to understand how the vascular connection to MS was dismissed, and why.
It's all about EAE (experimental autoimmune encephalomyelitis) and drugs.
Up until the 1930s, the prevailing thought was that MS was initiated by venous congestion. Dr. Tracy Putnam was at the center of this theory, blocking veins in dogs and creating MS-like lesions. Until a new doctor found a new, "simpler" animal model---
"In the early 1930s, Thomas Rivers and colleagues provided the first evidence that immune cells can attack the brain. Their simple experiments established what is now the most well-studied model of autoimmunity—the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.
Studies had shown that injection of foreign brain tissues into the brains of rabbits could cause paralysis (2). Intrigued, Rivers—then a virologist at The Rockefeller Institute—set out to duplicate these studies in monkeys. Rivers and his colleagues injected Rhesus macaques with normal brain extracts from rabbits and showed that most of the monkeys developed acute CNS disease with immune cell infiltration and demyelinating lesions. No infectious agent could be cultured from the animals, putting to rest suspicions of an infectious etiology. Rivers' group also noted that the disease-inducing capacity of the brain extracts paralleled their myelin content, providing the first hint that myelin was involved in disease induction. Thus, the experimental allergic (now “autoimmune”) encephalomyelitis (EAE) model was born. The group published these observations in three articles in the Journal of Experimental Medicine (3–5)."
EAE continues to be the medical model neurologists and immunologists study today, even though this model for MS is deeply flawed. Researchers continue to give mice EAE by injecting them with antigen, and then try to "cure" them with a variety of immune blocking or modulating medicines.
Here's a paper from 2005
"Experimental autoimmune encephalomyelitis (EAE) is a useful model for aiding the development of new treatments for MS. All therapies approved for MS ameliorate EAE. Two approved medications, glatiramer acetate and Natalizumab, were developed directly from studies in EAE. Several trials are ongoing in MS after success in EAE, including altered peptide ligands of myelin, DNA vaccines and statins. However, EAE has failed to predict the outcome of certai n approaches. The reasons underlying such failures are discussed here.
Many scientists interested in developing new therapies for MS criticize the EAE model for its poor record of predicting outcomes in the clinic, especially for those instances when promising therapies indicate that they are beneﬁcial in models of EAE, yet then fail in subsequent clinical trials.
Nevertheless, the EAE models are rapid, and can quickly give indications of whether a particular mechanism of action of a speciﬁc drug has merit when taken into an in vivo model that recapitulates many aspects of the human disease, MS"
So, the reason we still use the EAE model for MS is because it is a RAPID proof of DRUGS?
Because these drugs can cure mice of EAE?
MS researchers continue to use this disease model, to the exclusion of other research, even in light of the fact that these treatments appear to cure mice of EAE...but FAIL IN CLINICAL TRIALS OF HUMANS WITH MS.
Insanity is repeating the same action over and over again and expecting different results. We have had seventy five years of EAE research, and we are not closer to understanding MS.
Perhaps we need to find a new model?
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