Lymphedema is a disorder of the lymphatic vascular system characterized by impaired lymphatic return and swelling of the extremities and accumulation of undrained interstitial fluid/lymph that results in fibrosis and adipose tissue deposition in the affected area. It can be an inherited condition (primary lymphedema) or occurs after cancer surgery and lymph node removal (secondary lymphedema). It causes a significant morbidity and is a common disabling disease affecting more than 120 million people worldwide, however there is no curative treatment for lymphedema. Therefore, our main objective will be to establish a multiple gene therapy for lymphedema. We will focus on women who developed secondary lymphedema after breast cancer.

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In Western countries, cancer treatment is the major cause of lymphedema. Ten to fifteen percent of women develop lymphedema after surviving breast cancer. Recently, surgical procedure has been improved to minimize damage to the lymphatic system and thus to reduce lymphedema consisting in limiting lymph node excision to decrease the risk of developing the pathology. Despite the improvement of surgical techniques, lymphedema remains a frequent concern of cancer patients. Therefore, this project is focusing on women who developed secondary lymphedema after breast cancer. We are developing a regenerative gene therapy with non-integrative lentiflash vectors to restore the lymphatic function in the lymphedematous arm.

Secondary lymphedema occurs months, sometimes years after cancer surgery suggesting that lymphedema is not only a side effect of the surgery, but involves modifications of the lymphatic architecture as well as its microenvironment, in particular adipose tissue that accumulates in the limb. There is no cure for lymphedema because of the lack of identified therapeutic strategies able to restore collecting lymphatic draining function in the arm’s adipose tissues.

We are determined to find a treatment.

Therefore, Theralymph main objectives are to:

1/ Describe the physiopathology of lymphedema to better understand mechanisms of loss of lymphatic function.

2/ Identify therapeutic targets for lymphedema to restore the lymphatic flow.

3/ Validate therapeutic targets in preclinic models of lymphedema.

4/ Perform a Phase I/IIa gene therapy clinical trial on patients who developed lymphedema after breast cancer using lentiflash vectors.

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