Ceregene Inc., a biotech company developing treatments for neurodegenerative diseases such as Parkinson's disease, has presented new data demonstrating long-term, biologically-active expression of neurturin, a nervous system growth factor delivered to the degenerating dopamine nerves in patients with Parkinson's disease following treatment with CERE-120 (AAV2-neurturin).

Raymond T Bartus, Ceregene's chief scientific officer and executive VP, was invited to give a presentation entitled “The Development of AAV2-neurturin (CERE-120) for Parkinson's Disease: A Review of the Challenges and Translation Issues Confronted During the Course of Establishing 'Clinical Proof of Concept'” at the annual meeting of the American Society for Gene and Cell Therapy during the Clinical Trials I Symposium in Philadelphia.

CERE-120 is a viral vector engineered to deliver the nervous system growth factor neurturin (NRTN), which has the ability to rejuvenate degenerating dopamine-producing neurons, restoring function and keeping them alive. NRTN has been shown to safely protect and restore damaged nigrostriatal nerves in animal models of Parkinson's disease and appears safe in humans tested in four Ceregene-sponsored clinical studies enrolling a total of 120 patients, 80 of whom were administered CERE-120. A previous double blind-controlled human study demonstrated clinical benefit on several motor and Quality of Life (QOL) endpoints 12 and 18 months following CERE-120 delivery (with no measure favoring sham) and established clinical proof of concept in humans.

Dr Bartus will present histological evaluation of autopsy tissue from subjects administered CERE-120 to the brain who later died of unrelated causes. Analysis of brains from Parkinson's subjects 1.5 and 3 months post-CERE-120 treatment revealed NRTN expression in the targeted putaminal region of the brain, but only rare instances of NRTN-positive cells in the substania nigra (where NRTN was expected to be transported following putaminal treatment of patients in order to maximize induction of neuronal repair genes). This suggested impaired retrograde transport in these degenerating nerves in these PD patients. In addition, NRTN in the putamen was associated with occasional, sparse induction of the enzyme tyrosine hydroxylase (TH) needed for dopamine synthesis, suggesting suboptimal benefit was achieved due to the limited NRTN transported to the substantia nigra. Brains from 2 subjects 4-plus years post-CERE-120 demonstrated similar, targeted NRTN expression in the putamen, but importantly now showed evidence of increased transport of NRTN to the substantia nigra. Equally important, with more NRTN in the substantia nigra, the TH response is now appreciably larger, compared to the patients with shorter post-CERE-120 time points. Collectively, these findings are completely consistent with the predicted effects of CERE-120 following putaminal delivery and further support the idea of additionally targeting the substantial nigra directly with neurotrophic factors, including the approach employed in the ongoing double-blind, sham surgery-controlled CERE-120 trial.

“These data validate the clinical approach we have taken in our on-going, fully enrolled Phase II b double-blinded study of CERE-120 in Parkinson's patients, in which we are targeting both the substantia nigra and the putamen as well as utilizing an increased dose of CERE-120. Results from that study are expected in early 2013,” stated Jeffrey M Ostrove, Ph.D., president and chief executive officer of Ceregene, Inc. “I would like to thank the families of participants in our clinical studies, without whose courage and granting of permission for the autopsy, we could not have discovered these critically important scientific facts.”

Dr Ostrove further added, "I would also like to express our deep appreciation to the Michael J Fox Foundation for Parkinson's Research for their ongoing financial support of our clinical programme utilizing neurotrophic factors."

CERE-120 is composed of an adeno-associated virus (AAV) vector carrying the gene for neurturin, a naturally occurring protein known to repair damaged and dying dopamine-secreting neurons, keeping them alive and restoring normal function. Neurturin is a member of the same protein family as glial cell-derived neurotrophic factor (GDNF). The two molecules have similar pharmacological properties, and both have been shown to benefit the midbrain dopamine neurons that degenerate in Parkinson's disease. Degeneration of these neurons is responsible for the major motor impairments of Parkinson's disease. CERE-120 is delivered by stereotactic injection to the terminal fields (i.e., the ends of the degenerating neurons), located in an area of the brain called the putamen, as well as the cell bodies for these same neurons, located in a different area of the brain, called the substantia nigra. Once CERE-120 is delivered to the brain, it provides stable, long-lasting expression of neurturin in a controlled and highly targeted fashion.

Parkinson's disease is a progressive movement disorder that affects a million people in the United States. Its main symptoms, stiffness, tremors and slowed movements and gait, are caused by a loss of dopamine-containing nerve cells in the substantia nigra, which project their axons to the putamen. Dopamine is a neurotransmitter involved in controlling movement and coordination, so Parkinson's patients exhibit a progressive inability to initiate and control physical movements. There is currently no treatment that can reverse the degeneration of these neurons, let alone cure Parkinson's disease.

Ceregene Inc. is focused on the delivery of nervous system growth (neurotrophic) factors for the treatment of neurodegenerative and retinal disorders using gene delivery.

As the world's largest private funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today.