Selective Delivery of Drugs to the CNS for Treatment of Neurological Diseases
Brain diseases like Alzheimer’s disease, Parkinson disease and Multiple Sclerosis are among the most challenging to treat, often leading to poor outcomes for patients. A major obstacle in treating these diseases is delivering drugs effectively to the brain while minimizing side effects. This is because the brain is protected by barriers that make it difficult for most drugs to reach it. This thesis explores new strategies to deliver drugs selectively in the brain using peptide-drug conjugates. These conjugates are designed to transport drugs into the brain and release them only in the brain. The conjugates consist of three parts.
- A transporter (the peptide), that helps the drug to enter the brain
- A drug that targets a brain disease
- A linker that connects the two and only releases the drug upon reacting with the unique environment of the brain.
By ensuring the drug’s activity is silenced in the circulation and only activated in the brain, this method could reduce side effects and improve treatment effectiveness. The thesis explores two novel strategies for designing linkers. One is activated by an enzyme called acetylcholinesterase which is abundant in the brain. The other is activated by the brain’s high levels of reactive oxygen species. These approaches represent a promising step toward more precise and effective treatments for brain diseases.
Principal Supervisor:
Associate Professor Katrine Qvortrup, DTU Chemistry
Co-supervisor:
Professor Jens Øllgaard Duus, DTU
Examiners:
Associate Professor Sebastian Meier, DTU Chemistry
Professor Jarkko Rautio, University of Eastern Finland, School of Pharmacy, Finland
Professor Rasmus Prætorius Clausen, University of Copenhagen
Chairperson:
Associate Professor Charlotte Held Gotfredsen, DTU Chemistry