Scientific achievements during 2^nd year of the project

• We designed, synthesized and tested in high throughput assay a library of derivatives of existing GDNF mimetics.
• We identified a third generation GDNF mimetics that supported cultured dopaminergic neurons in nanomolar concentrations
• We constructed several different computational models that explain behaviour of existing GDNF mimetics, however, we have not reached high enough statistical quality to attempt reverse-QSAR to construct new compounds.
• We selected several novel potential GDNF mimetics based on the results of screening of small molecules libraries
• We made a proof-of concept in vivo study and demonstrated that the first generation GDNF mimetic can prevent the development of behavioural symptoms of Parkinson’s disease in vivo.

Team members overseas

During the second year of the project the secondments of the researchers were continued: Dr. Yulia Sidorova and MSc. Ilida Suleymanova finished their first secondments, and we sent one more early stage researcher, MSc. Karmen Kapp, from University of Helsinki (Faculty of Pharmacy) to join Molcode team in Estonia for four months.

We said goodbye to Dr. Girinath Pillai, who worked for 12 months in Molcode, developing linear and nonlinear models using a variety of techniques and helping our secondee visitors to get an idea of the many theoretical chemistry tools. Dr. Wei Li, an experienced researcher, was recruited to work on the solubility of GDNF mimicking compounds in University of Helsinki.

Heads out from the lab – All the contacts we made!

During the second year of the project, our team members reached out actively to spread information about the project. We opened our doors in University of Helsinki to students of different fields, as well as to high school students still considering what and where to start studying. Team members gave several scientific presentations around the world. We participated many medicinal and pharmaceutical industry-academy partnering meetings, and had partnering and dissemination activities with representatives of industrial sector.

The research goes on with the support of funding from EU

At the end of first half of the project we submitted our 1^st periodic report to the REA, Research Executive Agency of EU. After the approval of the report, we received the interim payment from EU to our project. This means that we can proceed with the project full speed and are continuing hard work towards the goal of the project; to find a cure for Parkinson’s disease.

Future plans (3^rd year)

During the third year of the project we are focusing on the following issues

• We will find out if first generation GDNF mimetics is able to protect dopaminergic neurons in vivo.
• We will access the activity of third generation GDNF mimetics for the ability to alleviate behavioural symptoms of established Parkinson’s disease and regenerated injured dopaminergic neurons in vivo.
• We will try to refine our computational models to make them suitable for design of novel more potent GDNF mimetics.
• We will purchase or synthesize potential novel GDNF mimetics and test their biological activity in in vitro
• We will attempt to improve solubility and ADMET properties of GDNF mimetics to improve their applicability for clinical use.