Neurodegenerative Diseases and Neuroprotection

Neurological diseases and disorders affect brain function. Neurodegenerative diseases and neuronal damage are some of the most difficult to treat diseases and conditions. Many efforts have been made to develop curative or ameliorative therapies; however, no comprehensive or universally curative therapy has been developed. Moreover, the incidence of occurrence of these diseases and disorders is projected to increase as the population ages.

Neuroprotection is particularly relevant for stroke, which is arguably one of the most feared cardiovascular events among healthy subjects as well as those with existing cardiovascular disease. The types of strokes observed in susceptible populations are changing as well. That is, there is a tendency for less hemorrhagic stroke and an increase in ischemic mediated stroke. Other than the use of various thrombolytic and fibrinolytic therapies that run their own risk for further bleeding in the brain there are few effective strategies for preventing or reducing the untoward and often devastating effects of stroke mediated ischemic brain injury. 

Neurodegenerative diseases targeted by the company include Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Ongoing research worldwide suggests multimodal etiologies, meaning that no single therapy has yet been developed for their effective treatment. There is clearly a need for effective therapeutic solutions.

In order for a drug to be therapeutically effective in the brain, it must be able to cross the blood brain barrier (BBB) and it must not induce neuronal damage; however, very few drugs are able to accomplish both objectives. For example, research conducted at Duke University has previously shown that neriifolin, which is structurally related to oleandrin, provides robust neuroprotection in rodent brain slice and whole animal models of ischemic injury. However, neither neriifolin nor the FDA-approved cardiac glycoside digoxin cross the blood–brain barrier.

We have obtained data establishing that our products are able to cross the BBB.

In collaboration with Duke University, in vitro assays employing excised mouse brain tissue were used to evaluate the neuroprotective activity of the company’s products PBI-05204 and PBI-04711.  A key difference between these two products is the absence of oleandrin and other cardiac glycosides from PBI-04711. The data demonstrated that oleandrin and other components of Nerium oleander plant provide protection against stroke mediated injury and certain neurodegenerative diseases. However, it was also determined that oleandrin could be removed from the product and still provide neuroprotection. PBI‑04711 provides significant protection from brain injury caused by neuroinflammation and related oxidative injury.

That work has led toward further R&D directed toward use of PBI-05204, PBI-04711, and PBI-01011 as safe and effective therapies in these areas. 

Further Information: See “Product Development” or “Contacts”.