Researcher's Decades-Long Pursuit Sparks Clinical, Commercial Success
doggedly pursuing his research into lubricin, a naturally occurring protein in
the body, for more than 30 years.
Research led by Dr. Gregory Jay offers promising treatments ranging from dry eye disease relief to aiding in orthopedic surgery
Gregory Jay, MD, PhD, first started studying lubricin (Proteoglycan 4) more than three decades ago, and never dreamed it would become his life’s work. Now his vision for the potential of this versatile and resilient protein is on the verge of being realized as a clinical and commercial success.
Lubricin, which occurs naturally in the body, functions both as a lubricant and an anti-adhesive. As a lubricant, it can improve medical outcomes involving areas of the body that involve mucosal barriers – such as eye, viscera and cartilage surfaces — by restoring or supplementing the lost mucin. As an anti-adhesive, it can protect vulnerable organs such as the bowel or joints from developing post-surgical scarring and adhesions.
A comprehensive preclinical model conducted by Braden Fleming, PhD, and Dr. Jay, both of the Center of Biomedical Research Excellence for Skeletal Health and Repair at Rhode Island Hospital, validated the ability of lubricin to restore lubrication and slow cartilage loss due to trauma or surgery. In addition, markers of inflammation and joint damage were improved. Results from initial clinical trials conducted in Europe and published in the journal Ocular Surface validate lubricin’s effectiveness in treating dry eye disease.
Lubricin creates a chemical boundary that prevents cells from attaching. This is most easily demonstrated
by drawing an “x” with lubricin in a petri dish. The “x” literally marks the spot as cells grow all around the lubricin, leaving the letter clearly visible.
Alternatively, a drop of water spreads on plastic that has been coated with lubricin, when normally it would bead due to the hydrophobic effects.
“Currently, we practice medicine one patient at a time,” said Dr. Jay, an emergency medicine physician at Rhode Island Hospital and professor of emergency medicine and engineering at The Warren Alpert Medical School and School of Engineering of Brown University. “Soon we’ll be able to stop a disease, to practice medicine a disease at a time.”
“For the most part in medicine, we are not curing anything but just helping to manage diseases,” Dr. Jay explained.
He said lubricin appears to delay or prevent osteoarthritis stemming from trauma, injury or even the wear and tear of aging. “We know that the inflammation process erodes cartilage; lubricin protects it and encourages natural lubricin to be expressed. This could have as significant an impact on protecting joints similar to the effect that a dental sealant has when protecting teeth,” Dr. Jay said.
Lubricin’s ability to lubricate joints, combined with the proven ability of the body to retain lubricin that is injected, could make an immediate and lasting difference in orthopedic patients. When a patient has arthroscopic surgery, the joint’s natural lubricant is washed away. This loss can hinder the body’s ability to preserve the cartilage that remains after trauma and surgery.
Validating research has revealed significant cartilage preservation and confirmed that the inflammation levels were reduced after lubricin was injected into joints. It is hoped that a future clinical trial will to confirm these outcomes.
The key to bringing this to fruition is that Dr. Jay and his colleagues have developed a scalable way using cells in the lab to manufacture lubricin. Dr. Jay launched a new company to advance this technology. He is now the co-founder and chief medical consultant for Lubris, the biotech company formed to develop and commercialize lubricin.
Based in Framingham, Mass., Lubris employs four people and is poised for rapid expansion from this first commercial venture.
Other potential applications of lubricin include the prevention of post-surgical adhesions by blocking cells from building tissues; treating carpal tunnel syndrome by preventing the growth of scar tissue; treating dry mouth, a common side effect for people in treatment for throat and neck cancers; and for inflammatory joint conditions such as gout.
In April 2017, Lubris negotiated an agreement with Novartis, a global health care company headquartered in Switzerland, to license ECF843, Lubris’ proprietary recombinant form of human lubricin, for ophthalmic uses outside Europe, including as a dry eye treatment. Under the agreement, Lubris retains rights to commercialize products outside ophthalmology.
Since 1985, Dr. Jay has been fascinated by lubricin and its potential, first as a graduate student and then as a doctoral and medical student at the State University of New York Stony Brook. He continued to pursue this interest when he came to Rhode Island Hospital and The Warren Alpert Medical School of Brown University. He credits the culture at Lifespan, the health system that includes Rhode Island Hospital, for helping transition his work from the research bench to the market and ultimately to the bedside.
“This was an example of leveraging the academic research partner to make something possible,” Dr. Jay said. “The leadership and staff within the Office of Research Administration at Lifespan is receptive to scientists pursuing research that must be commercialized in order to have broad impact on public health and medical care. Here at Lifespan we have a culture of transparent entrepreneurship … Lifespan gets it.”