As our population ages, brain diseases are increasing in prevalence. One in three people will develop a brain disease during their lifetime. Many of these conditions, especially neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease, represent a large unmet medical need lacking effective treatments. Understanding of the molecular mechanisms underlying neurodegenerative diseases has grown rapidly during recent years, allowing for the generation of sophisticated animal models of disease and identification of promising therapeutic targets. However, in contrast to the dramatic advances in cancer and heart disease treatment in the current “post-genome era”, the availability of new drugs reflecting these scientific gains to treat neurodegenerative diseases is still lacking. Currently there are only 6 drugs FDA-approved to treat for example Alzheimer’s disease, while there are >300 drugs FDA-approved to treat cancer. A major reason for this gap is the blood–brain barrier (BBB) that impedes drug penetration into the brain. The unique properties of the BBB enable tight regulation of the movement of molecules between the blood and the brain. Hence, 98% of small molecule drugs and all large molecule drugs are blocked by the BBB. This severely limits the opportunity to design new treatments for brain diseases. Thus, the potential upside for new technologies that successfully address the BBB is enormous. In this project we propose to exploit new ways to cross the impermeable blood-brain barrier (BBB) and thereby enable effective uptake and exposure of novel drugs at disease sites in the brain. In this project we have focus on developing new drugs to treat neurodegenerative diseases, with ALS as the first target. The project resulted in the design of the first line of potential drug candidates which will be further evaluated and optimized.
In this project 3 potential lead drug candidates were identified. Those will be further optimized and tested in relavant animal models for their efficacy and toxicity profiles. Data generated from studies of the optimized drug candidates will create basis for the patent appliaction protecting selected lead drug candidates. The primary indication remains ASL, however in a long-term we will extend the indication to other nerodegenerative disorders, such as Alzheimers disease.