On 22 May at 14:15 Kadri Toome will defend her doctoral thesis via Teams video bridge „Homing peptides for targeting of brain diseases“ .
Professor of Nanomedicine Tambet Teesalu (PhD (Developmental Biology), Institute of Biomedicine and Translational Medicine).
Senior Research Fellow Cornelis F.M. Sier (PhD, Leideni University, Netherlands).
Neurological diseases, especially age-related disorders, are widespread and due to aging population the frequency of neurological diseases is expected to rise quickly and reach epidemic scale in the next decades. The most common age-related brain diseases are neurodegenerative disorders - Alzheimer's disease and Parkinson's disease, and brain tumors. For all of these diseases, there is no effective treatment that could cure patients or stop the disease progression. Brain tumors have a very poor prognosis despite multimodal treatment, patients with most aggressive type of tumors live less than 1.5 years. Neurodegenerative diseases are not lethal, but the progressive course of the disease makes patients dependent on their caregivers and healthcare system, leading to so-called modern epidemic.
The treatment of neurological diseases is hampered because the central nervous system is protected by a variety of molecular mechanisms that prevent pathogens, toxins and blood cells from entering the brain tissue. The most important of these protective mechanisms is the blood-brain barrier. Only a few molecules with very specific properties can pass this protective barrier, but it remains impermeable to most molecules, including 99% of drugs.
In order to improve the treatment of age-related neurological disorders, it is important to advance the diagnosis of these diseases, new molecular markers are needed to make the diagnosis at a very early stage, before the onset of clinical symptoms. When diagnosed at an earlier stage, smaller amount of brain tissue is damaged and the emphasis could be on treating the disease rather than alleviating the symptoms. The next important step in the treatment of neurological diseases is to find molecules that are able transport drugs across the protective barrier to reach the affected brain tissue. An important strategy that could improve the treatment of brain diseases is application of nanotechnology for the treatment of neurological diseases. CNS targeting ligands can be attached to the surface of nanoparticles and drugs could be encapsulated inside the nanoparticles. In this way, it is possible to deliver drugs that have shown efficacy in cell assays by killing tumor cells or protecting neurons, but cannot, by themselves, pass through protective barriers in the brain when injected into the bloodstream.
The aim of this preclinical work was to find peptides that would be able to accumulate in the brain and could be used as targeting ligands in various neurological diseases to deliver contrast agents or drugs into affected tissue. To select the best targeting ligands, we developed a highly sensitive quantitative methodology that allows to compare multiple targeting peptides simultaneously in cell and animal experiments.