Modified peptides potential allies against prostate cancer and Alzheimer's disease

A century after scientists first succeeded in isolating insulin and using it to treat diabetes, peptides play an increasingly important part in modern pharmacy: Many peptide-based drugs – among them Ozempic – are attracting huge attention and a number of candidates are in clinical trials. More interesting doors are waiting to be opened, and in a new thesis at Uppsala University, Esther Olaniran Håkansson presents results that add valuable knowledge to the development of future treatments for prostate cancer and Alzheimer's disease.

“The fact that peptides generally display high selectivity, low toxicity and the ability to interact with the body's own systems makes them perfect building blocks for new drugs. At the same time, several scientific challenges remain. For example, we need methods to modify their structure in order to increase their bioavailability and ensure that they degrade at the right time. In our research, we have achieved results with the potential to pave the way for further progress,” says Esther Olaniran Håkansson, PhD student at the Department of Medicinal Chemistry.

In a study related to Theranostics – a discipline where radioactively labeled molecules enable combined diagnosis and treatment – ​​Esther Olaniran Håkansson focuses on GRPR, a receptor that is overexpressed in prostate cancer. By modifying the structure of RM26, a peptide designed to bind to GRPR, the team has achieved both clearer imaging and increased circulation time in the blood.

“Despite intensive research, early diagnosis and treatment of prostate cancer remains a challenge for healthcare. Theranostics enables detecting even the smallest tumor cells as well as monitoring how individual patients respond to treatment. By binding RM26 to the blood protein Albumin, we have extended its systemic half-life and in parallel developed a method to create clearer contrast in the PET camera. Still work remains, but we hope that our results will ultimately contribute to more effective care.”

As global life expectancy increases, neurodegenerative diseases are becoming more common and are currently deemed the fastest growing cause of death. Currently, over 55 million people are estimated to be living with Alzheimer's disease, and in the search for methods to strengthen our cognitive abilities, such as learning and memory, Esther Olaniran Håkansson has reconstructed the structures of the peptide-like molecule HA08.

“Here, we are working with a focus on inhibiting the IRAP enzyme, which in turn can generate nerve cell growth and cognitive improvement. HA08 is already widely used, but we are convinced that it holds further potential and have developed twelve variations of the molecule. Our results show that it is definitely possible to improve its properties, and that each attempt provides knowledge that hopefully brings us closer to new effective drugs for Alzheimer's disease.”

Friday 12 September, Esther Olaniran Håkansson will defend her thesis Novel Synthetic Strategies for the Development of Peptides and Peptidomimetics in Alzheimer's Disease and Prostate Cancer. Ten years have passed since she first enrolled in Uppsala University's Master of Science Programme in Pharmacy, and immediately after her dissertation, Esther will take the next step in her career as she takes on a position in the Swedish Armed Forces.

“I have experienced some truly amazing years at the Faculty of Pharmacy and I really want to express my gratitude to my supervisor Luke Odell for the opportunity to develop in an environment characterized by scientific generosity. As I am about to leave the Biomedical Center, I do it with new knowledge and friends for life, and I cannot imagine a better starting point for my professional journey.”

text: Magnus Alsne, photo: Mikael Wallerstedt, Ottilia Andersson a o