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Perseus' Technology

 

Inventors at Duke University School of Medicine have identified a novel therapeutic target for chemotherapy-induced hair loss. By blocking thymic stromal lymphopoietin (TSLP) with monoclonal antibodies, we prevent hair cycle arrest from chemotherapy-induced cytotoxicity.

This is intended to be administered to patients topically, subcutaneously, or intravenously by physicians before and during chemotherapy to delay the hair cycle entry before and while chemotherapy acts non-specifically upon hair follicle stem cells (HFSC). We have demonstrated this in vivo through wound-induction models where mice lacking the TSLP receptor fail to initiate hair cycling.

 

In addition, we have confirmed that TSLP is present throughout the hair regeneration cycle, necessary for wound healing-induced hair growth, and highly expressed during active hair growth. Experiments assessing the interaction of TSLP blockade with chemotherapy, any synergistic effects upon chemotherapy outcomes, as well as synergistic effects of TSLP with other hair growth stimuli are ongoing.

Anagen (hair cycle growth)

Anagen (hair cycle growth)

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TSLP expands CD34+ITGalpha6lo transit amplifying cells (TACs)

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(A)  Experimental timeline for hair growth analysis following s.c. TSLP (250 ng).

(B)  Quantification of skin area that has entered anagen. Data are from n = 3 mice per group.

(C)  Representative photos of mouse back skin after s.c. TSLP treatment.

(D)  Experimental timeline for analysis of TSLP-driven cell proliferation.

(E)  Representative flow cytometry plots of CD34+ cells.

(F)  Quantification of CD34+ cells pre-gated on live, single cells.

(G)  Quantification of total, live, EdU+ cells.

(H)  IFlow cytometry plots representing ITGα6 expression pre-gated on CD34+ cells.

(I)  Quantification of CD34+ITGα6 subpopulations.

(J)  Flow cytometry histogram overlay of CD34+ITGα6lo cells from TSLP- and
vehicle-treated groups.

(K)  Quantification of EdU+CD34+ITGalpha6lo. Graphs represent means of 2 experiments using 6–8 mice per group ± SEM.

∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.

Other Applications

This technology could also be used for alopecia patients not related to chemotherapy, whereby hair loss is a fundamental symptom. In addition, TSLP has been found to promote the growth and metastasis of several cancers including breast cancer, and thus its blockade could present a new adjuvant therapeutic strategy to chemotherapy and/or immunotherapy. Finally, hair loss is often an accompanying symptom of treatments for acne, bacterial and fungal infections, high cholesterol, clotting, seizures, blood pressure, aberrantly active immune systems, weight loss, depression, and gout. This new technology could therefore address hair loss as a symptom of these ailments and present a general treatment strategy.

Advantages

  • First-in-class approach to treat hair loss demonstrated in vivo

  • Long-lasting effects up to 45 days

  • May be administered locally

  • Anti-TSLP neutralizing antibody have been previously approved for asthma treatment

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