OXFORD, U.K.—With the goal of overcoming some of thelimitations posed by treatments currently available for glaucoma, gene-basedbiopharmaceutical company Oxford BioMedica PLC has teamed up with the renownedMayo Clinic of Rochester, Minn., to develop a novel gene therapy for thechronic eye disease.
According to the Mayo Clinic, glaucoma is characterized byvision loss and potential blindness due to damage of the optic nerve, andaffects more than 60 million people worldwide. Current treatment options aim toreduce intraocular pressure via eye drops or surgery, but these approachespresent significant challenges for the patient. For example, patient compliancewith effectively using eye drops on a daily basis can be very poor. Sometherapies can also present side effects that can restrict regular use.
Now, Oxford BioMedica and the Mayo Clinic are pursuing adifferent, more targeted approach to addressing this high, unmet patient need:using a novel gene therapy to provide long-term control of intraocularpressure, thus minimizing disease progression.
The collaboration builds on earlier preclinical researchconducted by Mayo Clinic researcher Dr. Eric Poeschla and his research team,which established initial proof-of-concept for this approach to treatingchronic glaucoma. In felines and primates, Poeschla and his colleaguessuccessfully delivered a protein encased in a viral delivery system called avector to a glaucoma-related target in the eye. The protein was aphosphorescent green, and when the vector reached its intended destination inthe eye, the vector's cargo gene produced the phosphorescent protein. The eyeturned green when viewed with ultraviolet light, then continued to glow greenafter the procedure.
"When we deliver these genes, we get sustained geneexpression for at least nine months and possibly longer," says Andy Danielson,technology licensing manager in the Mayo Clinic's Office of IntellectualProperty. "This also reduces intraocular pressure for at least nine months."
This work will now be extended thanks to the addition ofOxford BioMedica's LentiVector technology, a platform based onlentiviral-derived vectors that can safely and efficiently deliver asignificant amount of genetic information into cells. Oxford BioMedica'spreclinical and clinical studies suggest that a single administration of itsLentiVector platform products can provide long-term, sustained or permanentgene expression.
"Oxford BioMedica believes that its LentiVector genedelivery system is perfectly suited to tackle chronic diseases of the eye,"says John Dawson, the company's CEO, who adds that Oxford BioMedica has fivecore gene therapy programs based on LentiVector: a Phase I/II clinical trialfor ProSavin, a potential treatment for Parkinson's disease; and acollaboration with Sanofi in which Oxford BioMedica is developing fourLentiVector platform products for the treatment of ocular diseases.
In short, "we have the bomb, and they have the bomber," saysManu Nair, a technology-licensing manager at the Mayo Clinic.
The partners' agreement calls for them to undertake preclinicalstudies to establish the feasibility of treating glaucoma using LentiVectorgene delivery technology expressing a COX-2 gene and a PGF-2α receptor gene inorder to reduce intraocular pressure. The collaboration includes an option forexclusive U.S. rights to license Mayo Clinic's glaucoma technology, whichOxford BioMedica can exercise upon completion of preclinical studies. Specificterms of those licensing rights have not been released.
The use of gene therapy as a treatment for glaucoma wouldpresent a major paradigm shift in the current manner of patient care, notesDawson.
"This is probably because the necessary gene delivery toolshave been unavailable to allow efficient therapeutic gene delivery andexpression," he says. "Current treatment options for glaucoma aim to reduceintraocular pressure either through topical methods (e.g., eye drops) or eye surgery, however these approachesare not effective in all cases. Consequently, there remains a large unmetmedical need in a significant proportion of the patient population."
Danielson agrees: "This is a way to offer a new therapy forthose patients who are resistant to current therapies, and a way to deliver asingle dose of therapy that would provide long-term benefits—overcoming thechallenge of incorrect dosage and fluctuations in ocular pressure. The MayoClinic is excited about developing a new therapy for an unmet need, one that iseasier for patients to take, more consistently beneficial and has the potentialto reduce disease progression."
Although specific details of the commercial opportunity forthis collaboration have not been disclosed, according to Oxford BioMedica,glaucoma treatment sales exceeded $4 billion in 2007.
Mayo Clinic collaborates with Indian science leaders
ROCHESTER, Minn.—In mid-October, the Mayo Clinic alsoannounced it signed a collaboration agreement with a top science and technologyorganization in India, the Council of Scientific and Industrial Research(CSIR). The parties will work together on such topics as drug, device andbiomarker studies relating to heart disease, chemical biology and appliedgenomics and innovations in metabolomics.
"We are engaging the best minds to help our researchteams improve our fundamental understanding of disease and develop new, moreeffective therapies for our patients," said Dr. Eric Wieben, Mayo'sassociate dean for external collaborations, in a statement released by theclinic. "Strategic international research collaborations such as this withthe CSIR, India will help us achieve those goals."
CSIR, formed in 1942, is the premier industrial research anddevelopment organization in India. It includes technology and life scienceresearch and 39 national laboratories. The prime minister of India is the organization'spresident.