Aeolus Pharmaceuticals AEOL 11207 Subject of Research Grant from Michael J. Fox Foundation
Published December 22nd, 2009
Aeolus Pharmaceuticals, Inc. announced today that Dr. Manisha Patel, an associate professor from the University of Colorado Denver’s School of Pharmacy, has been awarded a grant from The Michael J. Fox Foundation for optimization of a series of metalloporphyrins such as AEOL 11207 for the treatment of Parkinson’s disease. The grant is one of six awards totaling $1.5 million granted to research teams working to develop potentially disease-modifying therapies for Parkinson’s disease. The funding was awarded under the Novel Approaches to Drug Discovery for Parkinson’s Disease program, made possible by funding from Elan Corporation, plc (NYSE: ELN), a neuroscience-based biotechnology company.
“The award by The Michael J. Fox Foundation for Parkinson’s Research provides important recognition and funding for AEOL 11207, an orally available catalytic anti-oxidant, and further validates the positive pre-clinical results we have seen this compound demonstrate in animal models of Parkinson’s disease,” stated John L. McManus, President and Chief Executive Officer of Aeolus Pharmaceuticals. “We remain committed to the advancement of care in patients with Parkinson’s disease.”
The Novel Approaches program is an important component of MJFF’s overall strategy of providing critical resources to underfunded areas of the drug development pipeline. Novel Approaches seeks to advance the development of therapeutic targets that already have some promising initial data, while engaging industry partner Elan as a potential follow-on funder for those projects with the greatest potential to bring new, transformative treatments to people living with PD.
“Orally active metalloporphyrins such AEOL 11207 that penetrate the brain hold tremendous therapeutic potential for the treatment of Parkinson’s disease in which reactive oxygen species and mitochondrial dysfunction are known to play a damaging role,” stated Manisha Patel, Ph.D. of the University of Colorado who has been actively involved in the development of metalloporphyrins for neuronal disorders for over a decade.
Oxidative stress is a well-defined therapeutic target for Parkinson’s disease (PD) and antioxidant therapy is one of the most promising neuroprotective strategies for its treatment. AEOL 11207 is a synthetic catalytic antioxidant that mimic the body’s own antioxidant defensive enzymes i.e. superoxide dismutases and catalase. AEOL 11207 penetrates the blood brain barrier and has shown high potency as an antioxidant. It was recently shown that oral administration of AEOL 11207 protected dopaminergic neurons in a mouse model of parkinsonism. This suggests the potential utility of AEOL 11207 or related compounds as therapeutic agents in Parkinson’s Disease.
The studies to be funded under the MJFF Grant will assess the pharmacokinetic profile of AEOL 11207 and related compounds following oral administration as well as efficacy in a preclinical model of parkinsonism. Additionally, AEOL 11207 and related compounds will be assessed for potential behavioral toxicity related to manganese accumulation. These studies will determine 1) the plasma and brain pharmacokinetic profiles of lead compounds, 2) their ability to protect dopaminergic neurons in the mouse MPTP model and 3) whether manganese accumulation from chronic dosing poses a risk for adverse behavioral effects.
Current therapeutic approaches to treat PD are associated with serious adverse effects and fail to provide long-term control of this inexorably progressive disease. Therefore, there is an urgent need for novel classes of therapeutic agents for the treatment of PD. This project can rapidly identify an orally active compound for the treatment of PD.
About Parkinson’s Disease
Parkinson’s disease is a chronic and progressive neurological disorder that is characterized by a number of symptoms including tremors, limb stiffness, slowness of movements, and difficulties with posture and balance. It is estimated that over 1.5 million people in the United States suffer from the disease. Parkinson’s disease is more prevalent in people over 60 years of age, and the incidence of the disease is expected to increase as the average age of the population increases.
About University of Colorado Denver
The University of Colorado Denver is located on two campuses, the Denver Campus and the Anschutz Medial Campus in Aurora, Colo. UC Denver offers more than 120 degrees and programs in 13 schools and colleges and serves more than 28,000 students.
About AEOL 11207
AEOL 11207 is a small molecule that catalytically consumes reactive oxygen and nitrogen species (free radicals). The compound is a manganoporphyrin that contains a positively-charged manganese metal ion that is able to accept and give electrons to and from reactive oxygen species (“ROS”) and reactive nitrogen species (“RNS”). Research has shown that ROS and RNS have important cell signaling roles, and through its interaction with RNS and ROS, AEOL 11207 appears to have multiple mechanisms of action including anti-oxidant and anti-inflammatory activities. AEOL 11207 is orally available and readily crosses the blood-brain barrier. In animal studies AEOL 11207 has demonstrated an ability to down-regulate oxidative stress and severe inflammation, which is responsible for tissue destruction that occurs as a result of Parkinson’s and other neurological disorders.
