Photo-mediated ultrasound therapy for treatment of cutaneous vascular malformations

ABSTRACT: Cutaneous vascular malformations (CVM), such as port wine stain (PWS) which occurs in 0.3–0.5% of newborns, are often a cause of great concern to patients for both medical and cosmetic reasons. Laser irradiation with flashlamp-pumped pulsed dye lasers, i.e. photothermolysis therapy (PTT), is currently the gold standard treatment for PWS. Most patients with PWS, however, fail to clear completely after PTT. Photodynamic therapy (PDT) offers an alternative method for treatment of PWS. PDT requires the systemic injection of photosensitizers, which necessitates the avoidance of sun exposure for up to a week after treatment, time-dependent infusion, and systemic side-effects with suboptimal treatment effect. Therefore, there is a strong clinical need for alternative and better treatment methods for PWS and other CVM. We have recently invented a novel, effective, and highly-selective anti-vascular therapy technique, termed Photo-mediated Ultrasound Therapy (PUT). PUT is based on microcavitations in blood vessels produced by synergistically applied laser pulses and ultrasound bursts. As demonstrated by our preliminary study in the rabbit ear model in vivo, PUT is capable of eliminating cutaneous vessels without causing unwanted collateral damage to the surround skin tissue, offering a promising alternative solution for treatment of CVM. The ultimate goal of this research is to address the long-standing gap in treatment of CVM by developing and commercializing our recently invented PUT technique. To achieve this goal, the project streamlines to achieve the technological transition, including the following milestones: (1) to build and verify the Phase I α-prototype in a chicken comb model, (2) to build and verify the Phase II β-prototype for human subjects, (3) to complete clinical studies, and (4) to define the regulatory approval pathway with the FDA. In this Phase I research, PhotoSonoX LLC, via the collaboration with the University of Michigan School of Medicine, will build a clinically ready α- prototype system, and test its safety and efficacy to pave the road to clinical studies in Phase II. The central hypothesis is that PUT can precisely remove cutaneous vessels without damaging surrounding skin tissue. To test this hypothesis, our research will focus on the following specific aims: Aim 1: Develop a clinically ready α-prototype photoacoustic (PA)-guided PUT system to treat CVM which can be tested in a clinically relevant chicken comb model in Phase I. Aim 2: Determine the efficacy and safety of PUT for treatment of cutaneous vessels via the studies in a clinically relevant chicken comb model in vivo. The outcome will be proof-of-concept that PUT can effectively and safely remove cutaneous vessels. The PUT system with the laser and ultrasound parameters determined via the studies in the animal model will also provide a clinical prototype for human studies in Phase II. We expect that the proposed PUT technique has a great potential to transform our care of patients with PWS and other CVM by facilitating targeted and precise anti- vascular therapy while reducing the treatment burden and side effects.NARRATIVE: What proposed here is the development and commercialization of our recently invented anti-vascular technique, namely photo-mediated ultrasound therapy (PUT), which can treat blood vessels in the skin safely and effectively. Once its efficacy and safety are validated via the proposed Phase I studies in a clinically relevant animal model in vivo, this technique will be ready for clinical studies in Phase II. PUT, holding a great potential for quick translation, could open an entirely new, effective, and selective therapy of vascular malformations such as port wine stain which occurs in 0.3–0.5% of newborns.