Type: Conference presentation
Presenter: Dr. Greg Blaney
Conference: 7th International Congress on Autoimmunity
Location: Ljubljana, Slovenia
Date: May 2010
Recent research highlights the importance of VDRThe Vitamin D Receptor. A nuclear receptor located throughout the body that plays a key role in the innate immune response. integrity and responsiveness on innate immune function. VDR knock out mice show both an increased frequency and severity of autoimmune disease and reduced ability to cope with bacterial infection and persistence. We have found that autoimmune disease in humans is associated with elevated levels of 1,25 OH Vitamin D indicating VDR resistance. Co-morbid conditions such as colitis, sinusitis, vasculitis and recurrent infections, reflecting intracellular or biofilm A structured community of microorganisms encapsulated within a self-developed protective matrix and living together. bacterial persistence, have been found by ourselves and others in autoimmune diseases. In silicoExperiment technique performed on computer or via computer emulation. modeling and clinical observation show that olmesartan medoxomil, an angiotensin receptor blocker, acts as a VDR agonistA substance such as olmesartan (Benicar) or 1,25-D which activates the Vitamin D Receptor and transcribes the genes necessary for a proper innate immune response.. Selected patients with significant and advanced autoimmune disease, including inflammatory arthropathy, autoimmuneA condition or disease thought to arise from an overactive immune response of the body against substances and tissues normally present in the body thyroiditis, ankylosing spondylitis, sarcoidosis, were treated with olmesartanMedication taken regularly by patients on the Marshall Protocol for its ability to activate the Vitamin D Receptor. Also known by the trade name Benicar. at dosing levels sufficient to activate the VDR along with bacteriostatic antibiotics at sub-inhibitory dose levels. During treatment, temporary exacerbation of symptoms and worsening of clinical markers were seen reflecting immune response. Physical manifestations included inflammationThe complex biological response of vascular tissues to harmful stimuli such as pathogens or damaged cells. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue. and swelling of joints, dermatitis, central and peripheral nervous system dysfunction, fever and fatigue. Laboratory changes included reduction in red and white blood cells, platelets; elevation in serum potassium, creatinine; and reduction in eGFR. After sufficient time of treatment, positive therapeutic responses that manifested included reversal of late-stage autoimmune conditions including carotid artery calcification, inflammatory joint disease, neuropathy, and osteoporosis. In addition normalization of clinical markers such as CRP,SED rate, kidney function were observed.
I will be presenting case studies of 3 severely ill patients suffering from classical autoimmune disease. Specifically, I will be reporting the remarkable improvements achieved through the stimulation of the immune response.
Stimulating the immune system in autoimmune disease appears counter-intuitive. However, recent research in microbiology has clearly identified the incredible capacity for microbes to persist in the body. This is achieved through a variety of mechanisms, one being the production of ligands that act as antagonists of nuclear receptorsIntracellular receptor proteins that bind to hydrophobic signal molecules (such as steroid and thyroid hormones) or intracellular metabolites and are thus activated to bind to specific DNA sequences which affect transcription..
Dr. Marshall and his colleagues have shown the presence of VDR resistance in autoimmune disease and that olmesartan is a VDR agonist with high affinity.
The following case studies show the clinical response to an immune stimulation protocol using olmesartan at doses of 40 mg 4 times per day.
Additional immune stimulation was achieved by the use of low dose bacteriostatic antibiotics to inhibit both bacterial virulence factors and quorum sensing signaling capabilities.
Case 1 is ankylosing spondylitis in a now 50 year old male. Onset was at the age of 26, initially as sacroiliitis. It progressed in a typical fashion with increasing rigidity of the spine, fusion of cervical facet joints, pain and fatigue. He also developed co-morbid conditions including chronic prostatitis, neuropathy, irritable bowel syndrome, insomnia and depression. He was unable to work full time.
He started treatment December 2005.
He experienced waxing and waning of symptoms both physical and emotional through the first 3 years of treatment, peaking in mid 2007. Presently he is no longer depressed and is back working full time in international finance. His prostatitis has cleared as has his IBS. Bone density increased 11% in his femur and 5% in his lumbar vertebrae over the last 2 years. His Bath Ankylosing spondylitis Disease Activity Index which had risen from 8.8 to 9.2 is now 5.3.
Case 2 is a 37 year old female who developed autoimmune arthritis 2 weeks after suffering from a STD. She rapidly deteriorated, developing dry eyes and mouth, Raynaud’s, paraesthesia, myalgia, malaise and dermatitis. Her diagnosis shifted from reactive arthritis to Mixed connective tissue disease.
She started olmesartan in October 2009. She improved rapidly. Today, she states that most days she feel “normal”, and only when trying to do physical things does she realizes that she’s not 100%. She can walk on the treadmill and do some light weights. She still need eye drops but only upon waking. She is back working full time.
Case 3 is 44 year old male diagnosed with severe and aggressive Rheumatoid Arthritis 8 years ago. Unresponsive to treatment, he was plagued by side effects including recurrent and severe infections, renal calculi, osteoporosis and massive weight loss. Prior to starting olmesartan, he had been on DMARDs since his diagnosis in 2002. He had used arthrotec, celebrex, plaquenil, gold injections, Enbrel, Fosamax, calcium, vitamin D and ibuprofen.
Now, a little more than a year after starting olmesartan, his inflammatory joint disease has diminished significantly. He has regained 25 kilos,and controls pain with low dose ibuprofen. His Stanford Health Assessment Questionnaire score has fallen from 3.0, in both disability and pain categories, to 1.5.
In none of these or any of the other patients treated, were there any serious side effects or infections.
These 3 cases were selected from a cohort of over 200 patients that I have either treated or collaborated on over the last 5 years. They were selected because they were advanced classical autoimmune disease and they highlighted several important aspects of the treatment. All had a history of exposure to microbes able to persist prior to onset of their autoimmune disease. Case #1 had severe acne and exposure to Hepatitis B. Case #2 had antibodies to parvovirus B19 and chlamydia pneumoniae. Case #3 was antibody positive to borrelia.
What do these and similar results suggest?
First, that olmesartan is safe and well tolerated at doses of 120 to 240 mg per day.
Second, it is an effective anti-inflammatory in autoimmune diseases via angiotensin II receptor 1 blockade and VDR agonist effects.
Third, olmesartan is a VDR agonist that does not cause hypercalcemia. Olmesartan induced VDR activation resulted in increased symptoms and changes in clinical markers reflecting immune stimulation. The increase in immune response leads to apoptosis of infected cells. The increase in released cytoplasmic peptides and increased effector T cell activity causes a combination of Jarisch-Herxheimer and IRIS like reaction. Increased pain, fatigue, transient skin eruptions, night sweats, episodic fevers were all commonly seen early in the treatment. Transient reduction in hemoglobin, white cell counts, fluctuations in sed rate & CRP, increased serum creatinine and uric acid were also not unusual. Serum levels of 1,25-DPrimary biologically active vitamin D hormone. Activates the vitamin D nuclear receptor. Produced by hydroxylation of 25-D. Also known as 1,25-dihydroxycholecalciferol, 1,25-hydroxyvitamin D and calcitirol. fell.
Fourth, that olmesartan and antibiotics at sub-inhibitory doses can, over time, prevent progression and often even reverse advanced autoimmune disease.
Fifth, that antibiotics used in this manner, provoke strong immune response, as indicated by clinical and laboratory reactions.
Sixth, low dose, pulsed bacteriostatic antibiotics, taken over a prolonged time are safe and are not associated with development of bacterial resistance or overgrowth of other pathogens such as C. difficile or candida albicans.
Finally, persistent infection is a likely cause of some autoimmune and chronic diseases that are associated with immune imbalance. The recognized capacity of bacteria to resist lysosomal degradation, to be able to transform into cell wall deficient forms, to communicate and share information, to create persister cells and the ability to establish biofilms A structured community of microorganisms encapsulated within a self-developed protective matrix and living together., all enable persistence. Any or all of these actions could then have a profound impact on immune capacity and tolerance. If so, it will explain some of the mysteries still existing in autoimmunity and open new opportunities for therapy.