Our genenetic heritage and autoimmunity

Back in the 1980s, after I was diagnosed with multiple sclerosis, I needed to discover, for my own satisfaction, the reason why. I quickly discovered that wouldn't be easy. Ever since 1873 when MS was recognized in England and featured in medical textbooks, scientists have been asking the same question, but where to start? I read that MS is an autoimmune disease in which the body's immune response attacks a person's central nervous system. So my first port-of-call browsing the Internet was AARDA - The American Autoimmune Related Diseases Association.

My grandmother, my aunt, my father and many members of my great-grandfather's family suffered from ankylosing spondylitis - a bone disease causing spinal curvature. It was so prevalent among family members that it gained the epithet, 'Newton back'. John Newton, born 1831 in Leeds, moved to Sheffield around 1850. My great-grandfather probably carried a defective autosomal gene affecting conversion of vitamin A into healthy bones. John Newton's eldest son, Frederick, fathered an illegitamate child, Percy, in 1898 by Emily Allsop. Although I met him only once, I remember my father's cousin, (he took his mother's name), was almost bent double with 'bamboo spine'. My father always blamed the curvature of his own spine on a childhood injury, falling on his back off a bridge into Porter Brook, but this is unlikely.

In 1993 I had been admitted to Royal Brompton Hospital, London diagnosed with a HOCoM is inherited as an autosomal dominant trait attributed to mutations in one of a number of genes that encode for one of the sarcomere proteins. About 60% of patients diagnosed with HoCOM will have a mutation identified in at least 1 of 9 sarcometric genes. Approximately 45% of these mutations occur in the myosin heavy chain gene on chromosome 14 q11.2-3, while approximately 35% involve the cardiac myosin binding protein C-gene.

Since it is typically an autosomal dominant trait, children of a parent with HOCoM have a 50% chance of inheriting the disease-causing mutation for this reason our three children had to be checked. Whenever a mutation is identified through genetic testing, family-specific genetic testing can be used to identify relatives at-risk. In individuals without a family history of HOCoM, the most common cause of the disease is a de novo mutation of the gene that produces the -myosin heavy-chain. An insertion /deletion polymorphism in the gene encoding for angiotensin converting enzyme (ACE) alters the clinical phenotype of the disease. The deletion/deletion genotype of ACE is associated with more marked hypertrophy of the left ventricle and may be associated with higher risk of an adverse outcome.

GENELOCUSTYPE
MYH7en14q12CMH1
TNNT21q32CMH2
TPM115q22.1CMH3 (115196)
MYBPC311p11.2CMH4 (115197)
??????CMH5
PRKAG27q36CMH6 (600858)
TNNI319q13.4CMH7
MYL33pCMH8 (608751)
TTN2q24.3CMH9
MYL212q23-q24CMH10
ACTC115q14CMH11 (612098)
CSRP311p15.1CMH12 (612124)

Five years later a cardiac septal ablation (ASA) a new procedure introduced in 1994 was successfully performed by the originator, Dr Ulrich Sigwart, the "Sigwart procedure", at Royal Brompton Hospital, London to reduce the thickening septum. My father's niece, Doreen Wilson, died of rheumatic fever aged 35. From another, different, autoimmune condition, At the autopsy the characteristic findings (thickened mitral valve, thickened chordae tendineae (hypertrophied left ventricular myocardium) were found.

Returning to MS which is caused by plaques on the myelin sheath around nerve fibres. This damage is caused when the body's defence mechanism (macrophages) attack myelin cells. But WHY? After all these years why haven't doctors and researchers found the answer to that question. Then I read the the following theory from two doctors working in Florida, USA:

"Based on the available scientific evidence we developed the concept that MS is primarily a disease of the vascular system and, only secondarily, an autoimmune disease. In other words, because of a failure of the vascular system, there is a localized ischaemia (decrease in blood flow) and an associated hypoxia (decrease in available oxygen). This hypoxia/anoxia (absence of oxygen) the myelin covering of the nerve axon dies. The dead myelin attracts macrophages (cells of the immune system that removes the debris) and elicits an inflammatory reaction. The proteins of the myelin that are released then elicits the immune response that people are familiar with.

This insight also provides new insight into the treatment of MS. In the therapy of MS, one should not be placing all emphasis on the immune reaction. There also should be treatment of the primary disorder. Unfortunately this is currently not being done although such therapy is available, has been used and has shown to be successful.

Just as it is wrong to treat only the immune aspect of the disease process without addressing the primary vascular cause of the disease, it would be equally wrong to treat just the primary vascular cause of the disease without paying attention to the immune reaction. In fact, in my latest publication, I suggest the combined use of therapy."

Sheldon F. Gottlieb PhD Ref: 1-4

So it appears that the elusive "environmental factor", is probably caused by a damaged vascular system unable to deliver suffient oxygen, leading to inflammation, myelin damage, and plaques but Dr. Pablo Villoslada, Institut Biomedical Research, Barcelona, adds a word of caution:

"Yes, the vascular theory was always there. But it seems that MS is more complex than that, with inflammation, degeneration and ischemia... but we are going to beat it for sure!"
As the cause of HCM is genetic, it seems logical to me that the underlying cause of MS must be genetic too. Read:

"The Viking Hypothesis" and the genetic link between MS and Scotland which has a much higher rate of MS than England, Wales or anywhere else in the world.

References
  1. Gottlieb, SF, Neubauer RA. Multiple sclerosis: its etiology, pathogenesis, and therapeutics with emphasis on the controversial use of HBO. Journal of Hyperbaric Medicine 1988; 3: 143 - 164.
  2. Gottlieb, SF, Smith JE, Neubauer RA. The etiology of multiple sclerosis: a new and extended vascular ischemic model. Medical hypotheses 1990; 33: 23 - 29.
  3. Gottlieb, SF. The case for hyperbaric oxygenation in multiple sclerosis. (Chapter 11). In: HYPERBARIC OXYGEN FOR NEUROLOGICAL DISORDERS. J. Zhang (Ed). Best Publishing Co., Flagstaff; 2008; 259 - 280.
  4. Gottlieb, SF The deadly influence of ideology in the treatment of multiple sclerosis. In: THE NAKED MIND; Best Publishing CO., Flagstaff; 2003; (Chapter 14) 339 - 394.

Since writing developments in this area are moving on apace. Read about Chronic Cerebrospinal Venous Insufficiency (CCSVI) and the work of Dr Paolo Zamboni, MD University of Ferrara, Italy on my next page CCSVI

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Last edited July 2011. ©Terence Wilson MMIX