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New approach in the treatment of rheumatoid arthritis

14.03.2006 - (idw) Zentrum für Molekulare Orthopädie

A group of Orthopedic surgeons from Düsseldorf have discovered a new class of biological compounds for the treatment of Rheumatoid Arthritis (RA). These compounds are called "anti-inflammatory exosomes". Treatment of 66 patients with RA proved successful using this technology. Exosomes are cell particles of white blood cells, which play an important role in the regulation of the immune system. Last Tuesday, Peter Wehling, M.D. of the Center for Molecular Orthopedics, Düsseldorf, Germany said: "Exosomes teach the immune system to recognize endogenous cells as endogenous again." Exosomes are small, not larger than 65-100 nanometers; which is approximately 10.000 - 100.000 times smaller than the diameter of a human hair. Düsseldorf 14.03.2006. Rheumatoid arthritis is a severe disorder of the immune system that causes inflammation of the joints. The immune cells attack endogenous joint cartilage and other connective tissue cells resulting in the destruction of the joint. Exosomes help the immune system regain its control and regulatory function. In total, Wehling treated 66 patients of different ages with severe RA with exosomes. None of the 66 patients treated had improved with conventional medical or surgical therapy significantly.

The patients received a single injection of exosomes into the most affected joint. "We observed quick and significant improvement in two thirds of the patients," said Wehling, who monitored the patients for follow-up periods ranging up to five years. The improvements lasted for an average of three to six months before exosome treatment was needed again. Significant improvement was achieved with respect to joint pain, joint swelling and lowering inflammatory markers like CRP and blood sedimentation rate. When the symptoms reappeared, the treatment was repeated and found equally effective.

"The discovery of the anti-inflammatory exosomes was rather incidental", said Wehling. "During the arthritis study we were doing with Harvard University we discovered that small particles, which migrated between the inflamed joints via the lymph system, had a surprising effect. When we injected cells into a joint for treatment, the joint on the opposite side of the body also improved. This effect did not fit the current understanding of arthritis or the role of the immune system in joint disease."

Further intensive research led the group to the discovery of anti-inflammatory exosomes, resulting in the isolation of a special form of these nanoparticles which had a powerful anti-inflammatory effect. Animal experiments in arthritic mice demonstrated high safety and efficacy of the endogenous particles in the treatment of arthritis.

"Based on the positive clinical results, antiarthritic therapy with exosomes appears feasible, safe and effective in cases of RA especially those who do not respond to basic conventional treatment" summarizes Wehling. In addition, exosomes may also be an option in the treatment of other immune diseases, like multiple sclerosis and allergies. Long-term studies are planned by the Düsseldorf group for the better understanding of the role exosomes play in immune health and disease.

800,000 individuals in Germany suffer from rheumatoid arthritis. It is a relapsing chronic disease, often leading to crippling changes and debilitation. RA also affects children and young adults. Approximately 12,000 - 15,000 children and adolescents are affected by the disease. The causes of this disease, commonly called "rheumatism" are still unknown. Conventional treatment is palliative and limited to anti-inflammatory drugs, steroids and surgery.

Contact:
Center for Molecular Orthopedics
Königsallee 53-55
D-40212 Düsseldorf
phone 0049-211-828937-10
Fax 0049-211- 828937-11
info@neue-orthopaedie.de
www.neue-orthopaedie.de

Public Relations
Antje Kassel
mobile 0049-173-2402901
antje.kassel@neue-orthopaedie.de

Literatur
Kim SH, Bianco N, Menon R, Lechman ER, Shufesky WJ, Morelli AE, Robbins PD: Exosomes derived from genetically modified DC expressing FasL are anti-inflammatory and immunosuppressive, Molecular Therapy, 2006 Feb;13(2):289-300. Epub 2005 Nov 7


Couzin, Jennifer, The Ins and Outs of Exosomes, Science, 24.06.2005, Vol. 308, 1862-1863

Kim SH, Lechman ER, Bianco N, Menon R, Keravala A, Nash J, Mi Z, Watkins SC, Gambotto A, Robbins PD: Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. The Journal of Immunology, 2005 May 15;174(10):6440-8

Evans CH, Ghivizzani SC, Herndon JH, Wasko MC, Reinecke J, Wehling P, Robbins PD: Clinical trials in the gene therapy of arthritis. Clinical orthopaedics and related research, 2000 Oct; (379 Suppl):S300-7.

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