Tag: AsclepiX


Experimental Drug Delivers One-Two Punch to Vision Loss

Experimental Drug Delivers One-Two Punch to Vision Loss

April 15, 2019

The following was originally published in Johns Hopkins Medicine’s Newsroom.

In studies with lab-grown human cells and in mice, Johns Hopkins Medicine researchers have found that an experimental drug may be twice as good at fighting vision loss as previously thought.

The new research shows that the compound, named AXT107, stops abnormal blood vessels in the eye from leaking vision-blocking fluids. These results build on previous research that showed the same compound stopped the growth of abnormal vessels in animal studies of the blinding disease diabetic macular edema and wet age-related macular degeneration.

Images of the mouse retina with a fluorescent fluid tracer. Diseased blood vessels allow the tracer to permeate nearby tissues. Vessels treated with AXT107 do not allow fluids to escape and exhibit clean crisp borders with surrounding tissue. (Courtesy of Aleksander Popel)

Diabetic macular edema and wet age-related macular degeneration are the leading causes of vision loss in the U.S. Approximately 750,000 Americans age 40 and older have diabetic macular edema, and wet age-related macular degeneration affects over 1.6 million Americans age 50 and older. Both diseases can eventually cause blindness if untreated.

Current drugs for diabetic macular edema and wet age-related macular degeneration focus on halting the growth of these abnormal vessels to preserve what vision is left. The current standard of treatment is monthly injections directly into the eye to suppress new blood vessel growth. These frequent visits can be a burden for patients due to the discomfort, a small risk for each injection and, for some patients, difficulty getting to the appointment because their vision is not good enough to drive.

“Our findings give us a better understanding of how this potential treatment stops the disease from progressing and does it more quickly, efficiently, and has a longer duration than current drugs used in people with vision loss of this kind,” says Aleksander Popel, Ph.D., professor of biomedical engineering at the Johns Hopkins University School of Medicine.

The study was published in the Feb. 21 issue of the Journal of Clinical Investigation Insight. The researchers have licensed the technology through Johns Hopkins Technology Ventures to Baltimore-Based AsclepiX Therapeutics LLC, which Popel co-founded and serves as chief scientific officer.

In healthy eyes, the cells that make up blood vessels are bound together by proteins residing on the surface of the cell that are directed into place by Tie 2, another protein. Tie2 proteins pack tightly together where cells meet their neighbors and act like Velcro to create a fluid-tight connection between cells in the blood vessel’s wall. In diabetic macular edema, the Tie2 proteins disperse across the cell and no longer can maintain the fluid-tight barrier between the inside of a blood vessel and the outside. Gaps form between the cells, allowing fluids to permeate into the surrounding tissue.

To understand how the drug they developed could strengthen these connections, the researchers designed a series of experiments to explore how AXT107 affects the control of Tie2 and the Velcro-like proteins.

In their first experiment, the researchers used cells derived from human blood vessels grown in the lab that mimicked those seen in wet age-related macular degeneration. When they added the AXT107 drug to these cells, the researchers found that AXT107 initiated a series of changes to cellular proteins. Using a technique to measure protein changes, the researchers found that Tie2 proteins seemed to migrate across the cell. Groups of Tie2 proteins began to congregate where cells met their neighbors, and began rebuilding connections with other blood vessel cells.

The researchers note that when observed under a microscope, the cells went from jagged-looking around the edges to having smooth and continuous outer edges that could be better suited for one cell to fit snugly against another. “It was like zipping them up with a zipper,” says Popel.

The researchers further tested whether these smooth cells could create a watertight barrier, which would be necessary to create a blood vessel that doesn’t leak. So they grew the cells in a single layer and tested whether fluid could pass through by pouring a fluorescent liquid on top of the cells and checking to see if any of the glowing liquid ended up underneath. The researchers observed that cells treated with 100 µM of the AXT107 drug allowed 2.5 times less dye through the cell layer than control cells receiving no drug. This showed the researchers that the drug helped blood vessel cells create a watertight seal between them.

The researchers next wanted to see if the same effect could be achieved in living blood vessels. They used a fluorescent dye to observe the blood vessels in the eyes of normal mice and mice genetically engineered to mimic human macular degeneration. In the healthy mice, the researchers observed glowing blood vessels with crisp edges and very little fluorescence outside of the vessel. However, in the mice with macular degeneration, glowing liquids passed through the blood vessels, blurring the barrier between blood vessels and the surrounding tissues.

The researchers treated the engineered mice with leaky blood vessels, like those seen in macular degeneration, with injections of the AXT107 peptide into the animals’ eyes. After four days, the researchers found that in mice treated with AXT107, about half as much of the fluorescent dye leaked from their vessels as in animals that received saline injections containing no drug. These results, say researchers, show that the AXT107 drug was able to seal up leaking vessels and prevent vision-blocking fluids from permeating into the surrounding tissue.

Popel says previous studies of AXT107 in animal models showed the drug lasted longer than current treatments by forming a small clear gel of slow-releasing drug in the eye. If proved effective in humans, patients might need only one or two injections to the eye per year, instead of the monthly injections that are the current standard of care.

Popel says AXT107 provides a new therapeutic approach that targets two clinically validated pathways for retina diseases while the anti-VEGF agents only target one aspect of the disease. “In addition to potentially improving the response for patients, the longer duration of AXT107 may allow for less frequent dosing, thus reducing the treatment burden for patients,” says Popel.

The researchers say they plan to test the AXT107 peptide for safety and efficacy in clinical trials of people with diabetic macular edema next year.

Other researchers involved in this study include Adam Mirando, Jikui Shen, Raquel Lima e Silva, Zenny Chu, Nicholas Sass, Valeria Lorenc, Peter Campochiaro, Jordan Green and Niranjan Pandey of the Johns Hopkins University School of Medicine and AsclepiX Therapeutics.

Funding for this research was provided by the Office of the Director of the National Institutes of Health (S10OD016374), the National Cancer Institute (F32CA210482, R01CA138264), the National Eye Institute (R21EY026148, R43EY025903, R01EY028996, R44EY025470), the National Heart, Lung and Blood Institute (R01HL101200), the Research to Prevent Blindness/Dr. H. James and Carole Free Catalyst Award, the Life Science Investment Fund and TEDCO.

NBP is the Head of R&D, JJG is the CTO, ASP is the CSO, and PAC is a consultant of AsclepiX Therapeutics, Inc. The terms of these arrangements are being managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.


Female Entrepreneurs Explain Why Baltimore Is a Great Place…

Female Entrepreneurs Explain Why Baltimore Is a Great Place for Tech

March 22, 2019

A recent study from Smart Asset ranked Baltimore as the No. 2 city in the country for women in tech. The study looked at four factors: gender pay gap for women in tech; income after housing for women; women as a percent of the tech workforce; and the percent change in tech jobs. Smart Asset noted that women make up almost a third of the tech workforce in Baltimore and that tech jobs grew by almost 30 percent between 2014 and 2017.

We in the Johns Hopkins entrepreneurial ecosystem already knew, of course, that ours is an inclusive one. Still, encouraged by this recognition — and in celebration of Women’s History Month — we asked female entrepreneurs what makes Baltimore such a great place for women in tech.

Wendy Perrow, CEO, AsclepiX Therapeutics

Wendy Perrow

Baltimore is a wonderful place for women leaders in biotechnology, as we have some of the most innovative technologies being created from the University of Maryland and The Johns Hopkins University! The richness of the intellectual property in Baltimore has led to me leading two companies in Maryland, with new technology from both institutions. As a member of Gov. Larry Hogan’s Life Science Advisory Board, we are working to make Maryland a top scientific hub by 2023.

The workspaces created by the University of Maryland BioPark and Johns Hopkins Technology Ventures’ FastForward allow us to keep working with our founders and creators of their innovative technologies in Baltimore. Our goal in Baltimore and Maryland as a whole is to create new and innovative products, vaccines and medical devices that can treat patients and reduce the treatment burden for unmet medical needs.

Brittany Young

Brittany Young, founder, B-360

Baltimore is a good place for women in tech because we are able to form our own communities within a larger ecosystem. Often, entrepreneurship can seem like a lonely journey, and being a woman in tech can seem even more isolating, but groups like Baltimore Women in Technology connect you with other like-minded women and opportunities for growth.

Kristen Valdes

Kristen Valdes, founder and CEO, b.well Connected Health

While the b.well team is spread out across the country, we can’t imagine our home base being anywhere other than Baltimore. Having spent my entire career working with the Centers for Medicare & Medicaid Services and world-class institutions such as Johns Hopkins and the University of Maryland, it made perfect sense to have our headquarters here.

Thanks to our close proximity to these leading health care organizations in the region, greater Baltimore has been a key player in b.well’s early success. We believe that Baltimore can be and should be the health information technology capital of the United States.

Kristin Yim

Kristin Yim (WSE ’20), project lead, Semester.ly

The Johns Hopkins University and all the administrators have been open to all my ideas, many of which are coming to fruition. I have a great support system here from the computer science department, Center for Leadership Education and student government. I’m part of Women in Computer Science, and I love being able to bounce new feature ideas off of the girls (and guys) that attend our meetings. It’s also given me the opportunity to mentor other girls and give advice on entrepreneurship and spread the word about the resources that are available.

FastForwardU has been great about giving us space to work, connecting us to other entrepreneurs and notifying us of grant opportunities. FastForward also got us an ad hoc legal consultation when we were really stressed on a deadline.

Aimee Martin

Aimee Martin, CEO, MileMarker

Baltimore has a strong and growing network of women in tech. Our top universities and effective government-supported programs recognize the value of women entrepreneurs who are solving important problems through their businesses. It’s a great place to build women-led ventures and a wonderful place to live.

Pava LaPere

Pava LaPere (KSAS ’19), president and co-founder, TCO Labs, project lead, EcoMap

The best part about Baltimore is the flexibility built into our entrepreneurial community and culture. There is the feeling that we should do what is right — not just what has been done or what is easiest. I think an environment that allows women in tech to thrive comes from this will to solve problems as well as the close-knit community we have. Baltimore may be a smaller city, but that makes for strong relationships, allowing us to build great support networks regardless of where we come from.

Carolyn Yarina

Carolyn Yarina, CEO and co-founder, Sisu Global Health

Baltimore has been an incredibly supportive ecosystem for Sisu Global Health. We are proud that the majority of our financing has come from the Baltimore area and we’ve had great mentors, peers and partners all concentrated here in Baltimore. There also are supportive groups and ecosystems for women entrepreneurs and women in tech (Baltimore Women in Tech, for example).

The ecosystem encourages involvement and giving back. Sisu’s co-founders speak to high school students about getting more girls into STEM, and entrepreneurship classes to provide an example to female entrepreneurs. Many of our peers do the same.

Still, there is more we can do to level the playing field and address the unconscious (and conscious) biases against women in tech. What I love about Baltimore’s culture is that we aren’t afraid to admit our shortcomings and to improve. I look forward to seeing that continued improvement.

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