mRNA Therapy to Restore Lymphatic Flow in Secondary Lymphedema

mRNA Therapy to Restore Lymphatic Flow in Secondary Lymphedema

Lymphedema is a common complication of breast cancer treatment, affecting approximately a quarter of patients. Those affected can have an uncomfortable, unsightly and sometimes functionally impaired limb prone to episodes of superficial infection. The aetiology and pathophysiology of lymphedema in patients with breast cancer appear to be multifactorial and are still not fully understood.Although conservative treatment techniques can be very successful in controlling symptoms, they do not afford a cure. In this situation of unmet medical need, it is essential to find a new therapeutic solution to treat lymphedema. The approach of the LYMPHARN project is based on dual mRNA strategy delivered by FlashRNA® vector targeting both lymphatic endothelium and surrounding adipose tissue function.

Inclusion Criteria:

• Women who developed upper limb lymphedema after surgery for breast cancer hormone receptor positive (HR+) more than 5 years,
• Age> 18 years,
• Body mass Index (BMI)<40,
• Stage 2 Lymphedema, moderate (defined by an increase in volume between 20 and 40% compare to the healthy limb),
• Lymphedema evolving during at least 6 months,
• Patient who adhere to optimized decongestive therapy, including a compression sleeve worn daily, integrated into an educational care pathway for the management of their lymphedema,
• Patients information and signed written consent form,
• Patients affiliated to a social security system.

Exclusion Criteria:

• HER2+ breast cancer triple positive,
• Other aggressive breast cancers (including triple negative and inflammatory breast cancer),
• Active cancer needing chemo- or radio-therapy,
• Metastatic breast cancer,
• Bilateral breast cancer,
• Upper limb peripheral arterial disease ipsilateral to the lymphedema,
• History of recent (< 3 months) upper limb deep venous thrombosis ipsilateral to the lymphedema,
• Previous shoulder or orthopedic surgery on lymphedematous arm
• Any abnormality of the opposite arm (arm without lymphedema),
• Trophic disorders on the lymphedematous arm,
• Last episode of cellulitis less than six months,
• Recurrent cellulitis,
• Patient participating in a clinical trial or having participated in a clinical trial within the previous 3 months or within 5 half-lives of any investigational product Immunosuppressive and anti-inflammatory treatments (topical and anti-inflammatory dermocorticoids and oral corticosteroids) in the 10 days before the injection or within 5 half-lives.
• Patient under judicial protection or enable to express consent,
• Females who are or plan to be pregnant or breastfeeding during the course of this study,
• Women of childbearing potential (WOCBP) who are sexually active and unwilling to use an adequate birth control method (hormonal or physical barrier),
• History of cancer other than breast cancer (excepted basalcell carcinoma),
• Any acute, chronic, or severe psychiatric condition that may interfere with participation in the study
• Unstable, clinically significant neurologic, psychiatric, cardiovascular (eg, pulmonary arterial hypertension, cardiac valvulopathy, orthostatic hypotension/tachycardia), pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, hematopoietic, or endocrine disease or other abnormality which may impact the ability of the participant to participate or potentially confound the study results.
• Known allergy to bovine proteins
• Vulnerable patients (persons deprived of their liberty by judicial or administrative decision, persons undergoing psychiatric treatment, persons admitted to a health or social establishment for purposes other than research) according to article L1121-6 of the Public Health Code.