TAK1 - regenerative therapy

Reference Number TO 02-00056

The Challenge
Acute inflammation and - much more important - chronic inflammation like in rheumatoid arthritis (RA) are a major challenge for the public health system. The financial and social impact of RA is substantial, both for the public health authorities and for individuals. From an economic standpoint, the medical and surgical treatment for RA and the wages lost because of disability caused by the disease add up to billions of dollars annually. Daily joint pain is an inevitable consequence of the disease, and most patients also experience some degree of depression, anxiety, and feelings of helplessness. For some people, RA can interfere with normal daily activities and limit job opportunities. RA  affects approximately 30 out of 100.000 people, which corresponds to about 2 million people in USA alone, and occurs mainly in the middle ages of 40 to 60 years.
RA is characterised by synovial inflammation and cartilage, bone and tendon destruction. It leads to an irreversible loss of joint function in affected individuals. Novel strategies to interfere with inflammation and to enhance tissue repair would have a significant impact for affected patients.

	Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases

The Technology
The invention is directed to methods and compositions in TAK-1 mediated regulation of Smad activity in the affected tissue. The signal mediator TAK-1 (transforming growth factor beta–activated kinase), a  central  mediator of inflammation, interacts with Smad protein resulting in a modulation of the Smad protein activity, including the BMP-mediated Smad activity. TAK-1 inhibition leads to downregulation of Smad protein activity, which results in corresponding downregulation of inflammatory  processes and leads to stimulation of osteogenesis at the same time. This inventive method can be used for a regenerative therapy in chronic inflammatory diseases such as e.g. rheumatoid arthritis. 
 

Commercial Opportunity
The technology is offered for in-licensing or co-development of an innovative regenerative therapy of e.g. rheumatoid arthritis by stop of inflammation and at the same time stimulation of bone regeneration.

Developmental Status

In vivo mouse data available, proof of concept in a rheumatoid mouse model achieved.

Patent situation
Pending European, US and Indian patent applications based on WO 2004/087862.

Further Reading
In vivo RNAi-mediated silencing of TAK1 decreases inflammatory Th1 and Th17 cells through targeting of myeloid cells. Courtiers et al. (2010), BLOOD 116 (18):3505pp.

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Kontakt:

Sabina Heim, Ph.D.
Technology Manager
Ascenion GmbH

T: +49 (0)531 6181-2090
F: +49 (0)531 6181-2098
heim@ascenion.de