VP Series of Drugs for Neurological Diseases

VP025 is our lead product candidate from a new series of drugs being developed for the treatment of neuro-inflammatory disorders.

We have successfully completed a double-blind, placebo-controlled phase I trial of VP025. This dose-escalation trial examined the safety and tolerability of three doses of VP025 in healthy volunteers. Results of the study demonstrated that multiple administrations of low, mid-level, and high doses of VP025 were safe and well tolerated when compared to placebo. No drug-related serious adverse events were reported.

We have also completed a considerable amount of preclinical work that has demonstrated the ability of VP025 to reduce inflammation in models of a number of neurodegenerative diseases, including Parkinson’s disease, Amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's Disease), and diabetic retinopathy.

During 2006, results from our VP025 preclinical program demonstrated the significant reduction of several inflammatory mediators in a model of diabetic retinopathy, a common complication of diabetes that eventually results in the loss of vision. Scientific evidence indicates that diabetic retinopathy is associated with chronic inflammation and neurodegeneration.

During the 2006 Scientific Sessions of the Association for Research in Vision and Ophthalmology Meeting, Dr. Kyle Krady, Assistant Professor of Neural and Behavioral Sciences, Penn State College of Medicine, presented the findings from a preclinical model of diabetes. These demonstrated that VP025 had a significant effect (p<0.05) on reducing the expression, in the retina, of several pro-inflammatory cytokines including IL-1, IL-6, and MCP-1, which are associated with diabetic retinopathy in this model. Concurrently, the intramuscular administration of VP025 resulted in the increased expression of both IL-10 and TGF-β, two potent anti-inflammatory cytokines. Based on information in the scientific literature and current research observations, this effect is believed to be mediated via the regulation of microglial cell activation. Microglial cells are inflammatory cells found within the central nervous system and in the retina.

Diabetic retinopathy occurs when diabetes damages the blood vessels inside the retina, the light-sensitive tissue in the eye. The macular edema, or swelling, associated with diabetic retinopathy is caused by fluid leaking from damaged blood vessels within the macula, the small and highly sensitive part of the retina responsible for detailed central vision. Diabetic retinopathy, which causes up to 24,000 new cases of blindness in the United States each year, is the major cause of blindness in diabetics and is estimated to affect 4.1 million Americans.

Results from a number of other experimental models have demonstrated the ability of VP025 to reduce inflammation across the blood-brain barrier and improve correlates of memory and learning function. Preclinical research carried out by Dr. Marina Lynch’s team from the Trinity College Institute of Neuroscience in Ireland demonstrated the ability of VP025 to reverse detrimental neurological effects of chronic beta-amyloid exposure. Beta-amyloid is the major component of the plaques found in the brains of Alzheimer’s disease patients and is implicated in the development and progression of this condition. Beta-amyloid has also been linked to increased activation of microglial cells and reduced memory and learning function. Dr. Lynch’s research demonstrated that VP025 both prevented microglial activation and preserved memory and learning function.

Dr. Lynch’s team also demonstrated the ability of VP025 to reverse age-related inflammation in the brain. The process of aging is associated with increased inflammation in the brain, resulting from activation of microglial cells, as evidenced by increases in inflammatory cytokines and a reduction in memory and learning function (measured as long-term potentiation). CD200, a protein that controls inflammation and maintains microglial cells in an unactivated state, decreases with aging. Treatment with VP025 reversed age-related decreases in CD200 levels in the brain, reduced levels of microglial cell activation, and restored memory and learning function.

Dr. Yvonne Nolan’s team from the Department of Anatomy/ Neuroscience, University College, Cork, Ireland, has demonstrated the ability of VP025 to prevent increases in levels of p38 MAP kinase, a key component of the inflammation-signaling pathway, regulating IL-1β, TNF-α, and other immune system responses associated with many inflammatory conditions. In a preclinical model of Parkinson’s disease, pretreatment with VP025 was shown to prevent both the increase in p38 levels and the associated death of dopaminergic neurons. The death of dopaminergic neurons in this model system leads to the onset of movement abnormalities that mimic those seen in Parkinson’s disease.