Researchers predict an increase in vascular diseases due to the aging of the population and the increasing prevalence of risk factors such as hypertension and diabetes. To meet this medical need, treatments and techniques that can keep blood vessels open will be essential. Research into vascular remodeling offers hope for improved treatments and a better prognosis for people with a range of vascular problems including peripheral arterial disease (PAD) and hemodialysis vascular access site failure.
Technology
Vascular remodeling is at the core of Proteon Therapeutics’ proprietary vasodilation drug development program. This technology focuses on elastases that modify the extracellular matrix of blood vessels, leading to immediate and persistent vessel enlargement. Local, permanent vasodilation could improve the medical outcome of common vascular surgeries, and may reduce treatment costs. Proteon Therapeutics’ first drug candidate, PRT-201 is in pre-clinical testing and is expected to enter human clinical study in early 2008. This agent has the following highly desirable characteristics:
Substantial Dilation - Vessels are dilated 15-75% greater than their original diameter, an effect no other agent can deliver.
Rapid Effect - Dilation is complete after as little as 5 minutes.
Localized Treatment - Dilation is limited to the treated segment. Natural inhibitors in the blood limit systemic side effects.
Persistent Change - Modifies the extracellular matrix, leading to relief from vasospasm and persistent dilation, both unique characteristics.
Safe - Vessels treated with PRT-201 do not rupture or form aneurysms and can be safely punctured with needles.
Easy to Use - PRT-201 can be applied topically to the external surface of exposed vessels during surgery, or injected through angioplasty catheters.
Clinical Development Programs
Proteon Therapeutics is currently pursuing clinical development programs for PRT-201 in two main areas: vascular access for hemodialysis, and peripheral arterial disease (PAD).
Vascular Access for Hemodialysis
Proteon’s first-in-man clinical study is in hemodialysis access - a large and growing market with significant unmet medical needs. Patients with kidney failure must undergo periodic external blood filtering with hemodialysis machines in order to remove fluid and metabolic byproducts from their blood. Vascular surgeons prepare patients for hemodialysis by creating high flow access sites in the body that can be connected to hemodialysis machines. These high flow access sites are created by connecting a medium-sized artery to a medium-sized vein, resulting in a “shunt” of blood through the vessels. There are two main types of chronic access sites: arteriovenous fistulas (AVFs), where the vein is surgically sewn directly to the artery, and arteriovenous grafts (AVGs), where the artery and vein are connected via a segment of artificial tubing. Unfortunately, these access sites are often difficult to create and prone to failure, resulting in treatment interruptions, hospitalizations, painful corrective surgical procedures, and premature death. Proteon believes there is potential for using PRT-201 as a therapy to facilitate the creation of more reliable dialysis access sites.
Peripheral Arterial Disease (PAD)
A second clinical focus for PRT-201 is PAD, another large market with great medical need. PAD is almost always secondary to atherosclerotic narrowing of arteries, with patients presenting with pain in legs while walking, a condition known as claudication. These patients often progress to pain at rest and skin ulceration. If not successfully treated, these patients can progress to gangrene and often require amputation of the affected limb. Based on PRT-201’s demonstrated ability to increase vessel diameter after injection into the arterial wall, we expect to see an improvement in walking distance with treatment of focal atherosclerotic narrowing, either in combination with balloon angioplasty or as a stand-alone therapy. In effect, PRT-201 acts like a “biological stent” that can be used in locations where metal stents frequently fail to provide a durable solution.
