Drug – bio-affecting and body treating compositions – Whole live micro-organism – cell – or virus containing – Genetically modified micro-organism – cell – or virus
Patent
1986-02-25
1987-12-29
Rosen, Sam
Drug, bio-affecting and body treating compositions
Whole live micro-organism, cell, or virus containing
Genetically modified micro-organism, cell, or virus
424 95, 4241951, A61K 3902, A61K 3574
Patent
active
047160381
DESCRIPTION:
BRIEF SUMMARY
The invention relates to preparations for preventing various arthritic afflictions, for alleviating symptoms of arthritic diseases and of other autoimmune diseases, and for their diagnosis.
The novel preparations are based on certain mycobacteria or on certain fractions obtained from mycobacteria. There were also developed certain clones of T-lymphocytes which can be used for diagnostic and therapeutic purposes.
BACKGROUND OF THE INVENTION
Millions of persons are afflicted with chronic forms of arthritis which are thought to involve autoimmunity to constituents of the joints or connecting tissues of the body. These conditions include rheumatoid arthritis, ankylosing spondylitis, Reiter's syndrome and other forms of reactive arthritis. The etiology of these diseases is not known, but previous infection with various microbes seems to act as an inciting circumstance in genetically susceptible individuals. For example, patients with rheumatoid arthritis may show unusual immune reactivity to mycobacterial antigens and immunization with the BCG strain of mycobacteria was found to lead to arthritis in 15 of 150 individuals. Ankylosing spondylitis has been associated with infection by Klebsiella or Yersinia species of bacteria and other cases of arthritis by Salmonella, Snigella, etc. There is no evidence of active infection of joints by these microbes in the vast majority of cases and it has been postulated that microbial infection may trigger an aberrant, autoimmune response of the individual against his own antigens present in the joints.
Adjuvant arthritis (AA) is an experimental model of arthritis inducible by immunizing susceptible strains of rats to Mycobacteria. The disease which develops about 12 days after immunization has many of the features of rheumatiod arthritis and AA has been considered to be a model of rheumatoid arthritis.
SUMMARY OF THE INVENTION
There are provided pharmaceutical preparations for the diagnosis, for the vaccination against, and for the treatment of various autoimmune diseases and especially of arthritic conditions. There exists a family of chronic arthritic conditions such as rheumatoid arthritis, ankylosing spondylitis or Reiter's syndrome which are thought to arise from autoimmune processes in which the joints and other tissues are damaged by the immune system of the patient.
The triggering factors are unknown but it is believed that the infection with certain microbial agents may be important.
Adjuvant arthritis is considered to be an experimental model of autoimmune arthritis inducible in strains of rats by immunizing them to mycobacterial antigens.
According to the present invention there are provided pharmaceutical preparations based on certain mycobacteria and on fractions derived from such mycobacteria.
We have found that various types of mycobacteria, such as Mycobacteria H-37 RA, M. kansasii, M. vaccae, and similar strains may be used as such or fractionated by the use of certain solvents to give a precipitate and a water soluble fraction, which latter is suitable for various vaccinations and curative purposes.
Mycobacteria H-37 can be fractionated by the use of an aqueous solution of acetone (66% acetone in water). There is obtained a precipitate (AP) fraction and an acetone soluble (AS) fraction.
The immune response to the AS fraction leads to resistance to adjuvant arthritis; clones of lymphocytes that respond to AS, upon inoculation into naive rats, protect these against subsequent induction of adjuvant arthritis. Inoculation of such clones of lymphocytes into rats suffering from adjuvant arthritis markedly hastens their recovery from the arthritis.
It has been found that clones of T-lymphocytes which cause adjuvant arthritis respond (proliferate) to the AP fraction, but not to the AS fraction.
The SP and the AS fractions are immunologically cross-reactive with proteoglycans of normal joint cartilage, and therefore adjuvant arthritis can be explained as a noxious autoimmune response to AP cross-reactive antigens of proteoglycans. Protection against adjuvant a
REFERENCES:
Jolles et al.-Chem. Abst., vol. 68 (Jun. 1968), p. 112335y.
Bahr et al.-Biol. Abst., vol. 73 (1982), p. 76033.
Watson et al.-Biol. Abst., vol. 69 (1980), p. 2847.
Collins-Infection and Immunity, vol. 20 (May 1978), pp. 430-438.
Rook et al.-Parasite Immunol., vol. 1 (1979), pp. 111 to 115.
Cohen Irun R.
Frenkel Ayala
Holoshitz Joseph
Rook Graham A. W.
Stanford John L.
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