A Lincolnshire Post-Polio Library Publication
24th January 2006
It has been a while since the last Polio Biology column and much has happened in the field of neurodegeneration since the last installment. It's too bad we don't have as much focused medical research that specifically targets the Post-Polio Syndrome, nevertheless we can learn much about ourselves from work occurring in the general field of neurodegeneration. Actually, in a very real sense, Post-Polio Syndrome is the result of neurodegeneration, or the loss of vitality, synaptic connections, and resilience of our motor neurons.
One of the facts about PPS that has always bothered me is the generally accepted cause of the syndrome as deriving from overuse. Two mental roadblocks for me in accepting this idea are:
In any event, late neurodegeneration must involve several steps. It is obvious that a prerequisite is a susceptibility to late spinal neurodegeneration. There is a very interesting study about late neurodegeneration, after physical damage to the spinal cord, published in 2003 entitled: "Discrete Gene Loci Regulate Neurodegeneration, Lymphocyte Infiltration, and Major Histocompatibility Complex Class II Expression in the CNS". The title is a mouthful. The rest of this installment will explain the significance of this article to our problems with PPS and to it's possible treatment.
The above study involved the experimental destruction of motor neuron axons (referred to as avulsion of the ventral roots of the spinal cord) in two genetically different strains of rats. The authors also crossed the two mating strains of rats and avulsed the offspring of these two mating types. Some rats developed a late neurodegeneration (as we with PPS) and some did not. The ones that did not had different genes in several areas of their chromosomal makeup which controlled immune responses in the spinal cord. The ones who did experience late degeneration had different genes in these locations.
Four points (genes) on rat chromosomes labeled VRA1, VRA2, VRA3, and VRA4 acted to determine susceptibility to late neurodegeneration. Three of these loci determined whether or not immune cells (white blood cells or MHC II cells would present in the damaged areas after the original lesions healed). The corresponding (Synectic) locations on human chromosomes controlling a late immune reaction in the spinal cord after recovery are 8q12, 8q22.1, and 1p35.2-36.11, and 16p13. To explain the chromosomal notation there are 22 pairs of chromosomes along with a pair of sex chromosomes in the human. The first number, e.g., 8 above, indicates the gene is on chromosome number 8. The q designates that the location is on the long arm of the chromosome. Each chromosome has a narrow area called a centromere which separates a long arm from a short arm. The chromosomes are observed after they are stained and the second number, 12, designates the staining band when counted out from the centromere. The location 1p means the first chromosome's short arm (p) and the numbers following indicates that the gene is within the bands 35.2-36.11.
Figure 1 Diagram of one human gene with its loci and designation criteria
(US Library of Medicine)
In the past three years researchers at the Karolinska Institute in Sweden have demonstrated the presence of immune activity in the spinal cords of people suffering the Post-Polio Syndrome but not in patients who had polio with no late neurodegeneration. This immune activity was detected by the presence of immune chemicals derived from the same immune cells discussed earlier. Physicians at Karolinska have treated patients with intravenous immunoglobulin, which cleared the intrathecal space and spinal fluid of these immune chemokines and cytokines which directly attack motor neurons. Several patients treated with IVIg reported an increased vitality and quality of life, less pain and fatigue, and a general decrease in symptoms. [4, 5, 6, 7]. The work, which indicated a genetic basis for late neurodegeneration, strongly implies that late neurodegeneration is the result of T lymphocyte infiltration and macrophage type II instigation controlled by specific genes (which control the production of cytokines and chemokines, immune chemicals resulting from immune activation within the spine). I believe these two lines of inquiry outlined above fit nicely together to give us a picture of what may be happening inside the spinal cord ventral roots in Post-Polio Syndrome. If so, some unresolved questions about PPS are closer to resolution:
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© Copyright Eddie Bollenbach 2006
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Document preparation: Chris
Think-tank, Cornwall, United Kingdom.
Created: 25th January 2006.
Last modification: 21st January 2010.
Last information content change: 26th January 2006.