The Development of CERE-120 (AAV-NTN) as a Novel Neurorestorative Therapy for PD: From Concept to Clinical Trials and Beyond
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Date: November 13, 2008
Time: 8:30 a.m. - 9:30 a.m.
Location: Pharmatek Laboratories, Inc.
Speaker: Raymond T. Bartus , Ph.D., Executive VP and CSO, Ceregene
Presentation Summary
Understanding and treating neurodegenerative diseases represents one of our most important and growing medical challenges. While research continues to elucidate the etiologic and pathologic variables responsible for some neurodegenerative diseases, it has also exposed their complexity. Indeed, many now argue that each likely represents a syndrome, rather than a single disease, each sharing important characteristics but not a single cause. This reality greatly complicates any attempt to find or develop an effective therapies for these diseases. Certainly, identifying a single entity that may treat a disease, independent of which of several multiple causes or pathogenic pathways is involved, represents a formidable challenge.
Neurotrophic factors are naturally occurring proteins that may represent a viable approach toward satisfying this challenge. Basic research spanning several decades has demonstrated that when the appropriate neurotrophic factor is delivered to degenerating neurons, it is able to restore lost function, repair morphological damage and protect against further degeneration and death. Despite substantial translational interest, all past efforts to use them as therapeutics for human diseases have failed. Most authorities believe these failures are due to enormous difficulties of delivering these large proteins selectively to the targeted area in a sustained fashion.
Ceregene is focused on using neurotrophic factors to treat serious neurodegenerative diseases, employing gene transfer to solve the age-old problems of successfully delivering proteins to the CNS. Thus, rather than attempt to deliver the neurotrophic factor, we selectively deliver an AAV gene transfer vector engineered to contain only the therapeutic gene to the site of neurodegeneration. Thereafter, the therapeutic protein is persistently expressed locally at steady state (i.e., the ultimate ‘sustained release’ paradigm).
Ceregene’s lead program involves CERE-120 (AAV-neurturin) for treating the motor deficits of Parkinson’s disease. Nonclinical studies show that CERE-120 can be safely administered via stereotactic surgery to the putamen, provides predictable, controlled and steady expression of neurturin (likely indefinitely), produces no side effects and protects degenerating nigrostriatal dopamine neurons in a host of well-characterized rat and monkey models of Parkinson’s disease.
An open-label Phase 1 trial with CERE-120 (or AAV-neuturin) revealed no serious adverse events and an apparent 36% improvement on motor scores (UPDRS-off; n=12, p <0.001) and secondary efficacy motor end points. Long-term follow up assessment suggests the improvement persists for at least 24 months. Enrollment was completed for a multi-center (9 sites), double-blinded, sham-surgery controlled trail (n=58) and data is expected near the end of 2008.
About the Speaker
Dr. Bartus has over 30 years of experience in the pharmaceutical and biotech industries, involving tenures both at major multi-national companies and smaller, development-stage companies. Dr. Bartus joined Ceregene in December, 2002 and directs all preclinical, clinical and regulatory activities as well as chairs the company's SAB meetings.
Prior to joining Ceregene, Dr. Bartus spent 10 years at Alkermes, where he served as Senior Vice President for Preclinical Research and Development. During his tenure at Alkermes, he was directly responsible for the conceptualization, preclinical development and initial clinical strategy for Alkermes' lead proprietary product, Vivitrol (formally called Vivitrex), which has since gained FDA approval.
Dr. Bartus was selected to launch and served as Chief Editor for the scholarly journal Neurobiology of Aging. During his 10 years as Chief Editor, it grew to rank as the leading specialized journal in its field. He has also been selected to serve on numerous panels and "think tanks", including for the U.S. Congress' Office of Technology Assessment, Secretary of Health and Human Services, and FDA, among others. He is recognized as one of the founders of the 'Cholinergic Hypothesis', a hypothesis that led directly to the first four drugs approved by the FDA for Alzheimer's disease. He has been honored by ISI (the Institute for Scientific Information) as a "highly cited" researcher, comprising less than 0.5% of all publishing scientists. In addition to helping discover and develop several novel therapies for human diseases, Dr. Bartus has published nearly 250 scholarly papers, chapters, books and special journal issues.
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