Project: Novel recovery treatment for Stroke: enhanced brain delivery of Cyclosporin A

GOAL_x000D_UNSTROKE brings together the separately developed technologies of the high tech SME’s to-BBB and NeuroVive. The resulting product is expected to have potential as a drug for the recovery of stroke patients. Such a drug could significantly reduce the impact stroke has on the quality of life and revolutionize the way stroke is treated. Allowing patients to recover from stroke will also reduce the substantial economic burden on society due to the loss of employability. _x000D__x000D_The endpoint of this Eurostars project is the completion of the preclinical package which is required for the initiation of the first clinical studies in man. The consortium members will have their Investigational New Drug (IND) application submitted at the authorities (EMA and/or FDA), so clinical studies can be initiated as soon as IND approval is granted._x000D__x000D_BACKGROUND_x000D_-Stroke_x000D_A stroke is the rapidly developing loss of brain function(s) due to disturbance in the blood supply to the brain. By the deprivation of a proper blood supply, stroke causes tissue infarction and malfunction of neural networks, leaving stroke patients with permanent cognitive, sensory or motor deficits. Patients with limited neurological damage can regain (partial) functionality. However, in many cases (partial) inability persists. Consequently, besides the significant morbidity associated with the permanent loss of functions required for once daily routine, stroke imposes a substantial economic burden on individuals and society by removing stroke patients from the productive community. Stroke is the leading cause of adult disability in Europe and the United States and the second leading cause of death in the Western world, ranking after heart disease and before cancer, causing 10% of deaths worldwide._x000D__x000D_Currently, the development of safe and efficacious neuroprotective treatments represents the greatest unmet need in the management of stroke. In addition, key opinion leaders believe that the second most important unmet need in stroke patients is the development of neuroregenerative or neurorestorative (neurotrophic) treatments that are able to regenerate or replace damaged cells. _x000D__x000D_CONSORTIUM & TECHNOLOGIES_x000D_-NeuroVive technology: Cyclosporin A for neurological damage_x000D_In recent years it has become apparent that the immunosuppressant Cyclosporin A (CsA) also has neuroprotective properties, and possibly even neuroregenerative and neurorestorative properties (see 2.2.2.3 for working mechanism). An attractive feature of CsA is that it has already been approved by the FDA for other purposes, and for off label use. NeuroVive is exploiting the neuroprotective properties of CsA by developing the CsA formulation NeuroSTAT® as a treatment for traumatic brain injury (TBI). Animal studies show that CsA is protecting the brain from further damage. NeuroVive is currently initiating the clinical phase II/III studies for this product on the indication TBI._x000D__x000D_CsA has been used off label for stroke, but well documented patient studies are lacking. CsA poorly penetrates the brain as it does not readily cross the blood-brain barrier (BBB), that shields the brain from unwanted substances in the blood (including unknown molecules like many drugs). Where TBI damages the BBB allowing CsA to reach the affected brain area, this is not the case during ischemic stroke. Thus, in stroke patients CsA formulated as NeuroSTAT® can not efficiently reach the affected areas to function as a neuroprotective, neuroregenerative, and/or neurorestorative drug._x000D__x000D_-to-BBB technology: transporting molecular cargo across the BBB_x000D_Currently, there are only few approaches for brain drug delivery, which are limited in their application, as they are highly invasive or disruptive to the BBB (see 2.2.2.2). to-BBB’s unique G-Technology® is an elegant nanotechnology using a non-essential but native receptor molecule present in the human BBB to safely transport molecular cargo across this barrier, without disrupting BBB integrity (see 2.2.2.1 for working mechanism). All individual G-Technology® components (and some combinations thereof) have already been safely used in humans. Furthermore, to-BBB’s first G-Technology® based product (brain-targeted chemotherapy to treat Brain Cancer; 2B3-101) is currently entering clinical phase I._x000D__x000D_-Joining technologies: UNSTROKE_x000D_CsA has physical properties that are likely to be compatible with G-Technology®. Therefore, it is likely that CsA can be formulated as G-Technology® cargo, to allow efficient delivery of active CsA to a brain with an intact BBB, as is the case for patients that have experienced ischemic stroke._x000D__x000D_MARKET POTENTIAL_x000D_Every year there are more than 900.000 new stroke cases in Europe alone. As advanced age is one of the most significant stroke risk factors, and Western society is aging, stroke could soon be the most common cause of death worldwide. This means that the market potential for the drug that NeuroVive and to-BBB are jointly developing here is enormous._x000D_

Acronym UNSTROKE (Reference Number: 6337)
Duration 01/06/2011 - 31/12/2014
Project Topic For this project, two highly innovative European SMEs join forces to develop a potential new treatment for stroke patients: NeuroVive's cyclosporin A for the treatment of neurological damage will be combined with to-BBB's technology to deliver the active drug across the blood-brain barrier.
Network Eurostars
Call Eurostars Cut-Off 6

Project partner

Number Name Role Country
2 to-BBB technologies B.V. Coordinator Netherlands
2 NeuroVive Pharmaceutical AB Partner Sweden