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A novel companion biomarker for glaucoma
NEW YORK—Aimed at preventing vision loss and eventual blindness, Q BioMed Inc., a biomedical technology accelerator, has acquired an exclusive option to a novel gene biomarker for glaucoma from researchers at Washington University in St. Louis.
The biomarker—growth differentiation factor (GDF)-15—has been shown by Washington University School of Medicine researchers to be associated with retinal ganglion cell death and is upregulated in mouse models of chronic glaucoma. The key fact is that investigators have also linked GDF-15 expression to glaucoma severity in human patients.
The terms of the deal call for Q BioMed to evaluate the feasibility and utility of GDF-15 as the basis of a companion diagnostic for MAN-01, a small-molecule treatment for primary open angle glaucoma under development by partner Mannin Research. Additional terms of the agreement were not disclosed.
“The ophthalmology field in general, and glaucoma sector specifically, are currently in an active consolidation and business development cycle,” states Denis Corin, CEO of Q BioMed. “Having access to a truly innovative technology that complements ours—as a companion diagnostic—could greatly enhance the value of the Mannin Research MAN-01 technology.”
“We are excited to evaluate this technology and look forward to a new collaborative partnership with a leading institution like Washington University School of Medicine,” Corin adds.
Glaucoma is one of the leading causes of blindness worldwide, estimated to affect nearly 100 million people by 2020. The disease is linked to the buildup of pressure within the eye. When this intra-ocular pressure mounts, it can damage the optic nerve, and if the damage progresses, glaucoma can lead to permanent vision loss.
George N. Nikopoulos, president and CEO of Mannin Research Inc., tells DDNews that “the collaborative partnership between Q BioMed and Washington University, at this stage, is an opportunity to evaluate the feasibility of commercializing the use of GDF-15.”
“Our analysis includes patient and physician needs assessments, reimbursement strategy for usage of the biomarker in a clinic and conducting a feasibility analysis on the development pathway of the GDF-15 as a novel biomarker for glaucoma,” Nikopoulos says. “If the evaluation of GDF-15 leads to a potential commercial product, the two parties would formalize a license-based collaborative partnership.”
“This platform has the potential to enable a new generation of biomarkers that could make a positive impact upon the treatment decisions for millions of glaucoma patients,” he adds. “There are approximately 60 million patients with glaucoma around the world.”
The potential for utilizing GDF-15 as a biomarker to assess the severity of glaucomatous neurodegeneration was recently reviewed by Washington University’s Dr. Rajendra S. Apte, in the January 2018 Trends in Molecular Medicine article titled “Monitoring Neurodegeneration in Glaucoma: Therapeutic Implications.”
“Because vision loss in glaucoma is not reversible, therapeutic interventions early in disease are highly desirable,” the article states. “However, owing to the current limitations in evaluating glaucomatous neurodegeneration, it is challenging to monitor the disease severity and progression objectively, and to design rational therapeutic strategies accordingly. As such, in our opinion, molecular biomarker(s) that specifically reflect stress or death of RGCs, and which correlate with disease severity, progression and response to therapy, are highly desirable.”
Progression of glaucoma is typically monitored through a visual field test, but there has not been a reliable way to measure which patients have a high risk of rapid vision loss—until now.
Washington University researchers discovered GDF-15 to be a biomarker for glaucoma using an array analysis, which identified chemokines, growth factors, TGF-beta family members and other ligands whose expression increased in the optic nerve crush model of glaucoma, but not in endotoxin-induced uveitis or light-induced retinal degeneration models.
Washington University also validated GDF-15 in both rat models of glaucoma and in patients, showing that its expression correlates with disease severity. Overall, GDF-15 represents an attractive biomarker for glaucoma with distinct advantages (i.e., early detection) over conventional clinical tests and has the potential to be a first-in-class diagnostic test. The researchers’ findings of GDF-15 were published online May 4, 2017 in the journal JCI Insight.
“Other glaucoma tests are measuring cell death, which is not reversible, but if we can identify when cells are under stress, then there’s the potential to save those cells to preserve vision,” Apte states in the journal article. Apte is also a professor of developmental biology, of medicine and of neuroscience.
Glaucoma “often begins silently, with peripheral vision loss that occurs so gradually that it can go unnoticed,” according to Apte. “Over time, central vision becomes affected, which can mean substantial damage already has occurred before any aggressive therapy begins.”
Many patients “start receiving treatment when their doctors discover they have elevated pressure in the eye,” he explains. “Those treatments, such as eye drops, are aimed at lowering pressure in the eye, but such therapies may not always protect ganglion cells in the retina, which are the cells destroyed in glaucoma, leading to vision loss.”
“Glaucoma specialists attempt to track the vision loss caused by ganglion cell death with visual field testing. That’s when a patient pushes a button when they see a blinking light. As vision is lost, patients see fewer lights blinking in the periphery of the visual field, but such testing is not always completely reliable,” according to the paper’s first author, Dr. Norimitsu Ban, an ophthalmologist and a postdoctoral research associate in Apte’s laboratory.
“We were lucky to be able to identify a gene and are very excited that the same gene seems to be a marker of stress to ganglion cells in the retinas of mice, rats and humans,” Ban says.