University of Helsinki Researchers Find a Molecule (BT13) that has Therapeutic Potential Against Parkinson’s Disease

University of Helsinki Researchers Find a Molecule (BT13) that has Therapeutic Potential against Parkinson’s Disease

University of Helsinki researchers made a breakthrough in their discovery that a molecule known as BT13 has the potential as a therapeutic for Parkinson’s disease. In preclinical research studies including in vitro and in vivo studies in mouse models, the Finnish team reported their results in the journal Movement Disorders. The preclinical investigators have received support from Parkinson’s UK and others.

Researchers at the University of Helsinki’s Institute of Biotechnology Centre of Excellence in Molecular and Integrated Neuroscience have developed an exceptional center of excellence targeting work on the structure and function of neuronal growth factors and their targets in brain development, neuronal signaling and basic mechanisms of disease.

The Problem

There is no cure for Parkinson’s disease. Present day drugs can potentially alleviate symptoms but fail to halt the marching neurodegeneration. Over 6.2 million are afflicted with the disease. The disease is caused by degeneration and progressive loss of nigrostriatal dopamine neurons.

The Study

The team noted that Glial cell line-derived neurotrophic factor (GDNF) can protect and repair dopamine neurons in vitro and in animal models of Parkinson’s disease however the clinical use of GDNF is complicated by pharmacokinetic properties. Consequently, the research team sought to evaluate the neuronal effects of a blood-brain-barrier penetrating small molecule GDNF receptor Rearranged in Transfection agonist, BT13 in the dopamine system.

During the study the Helsinki team characterized BT13’s ability to do the following:

·       activate RET in immortalized cells

·       support the survival of cultured dopamine neurons

·       protect culture dopamine neurons against neurotoxin-induced cell death

·       activate intracellular signaling pathways in both in vitro and in vivo

·       regulate dopamine release in the mouse striatum and BT13’s distribution in the brain

The preclinical investigators found that BT13 potentially triggers RET and downstream signaling cascades such as Extracellular Signal Regulated Kinase and AKT in immortalized cells as summarized by Movement Disorders in Wiley Online. They report that BT13 actually supports the survival of cultured dopamine neurons from wild-type however not originating from RET-knockout mice. Moreover, the molecule secures cultured dopamine neurons from 6 Hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+)—induced cell death only if they express RET. Also, they found that the molecule is absorbed in the brain while also activating intracellular signaling cascades in dopamine neurons in both in vitro and in vivo and triggers the release of dopamine in the mouse striatum

Consequently, the team’s work, as summarized online, reveals that BT13 demonstrates potential as a future treatment for Parkinson’s disease.

Study Funders

The following organizations are identified as contributors to this research:

·       Genecode Ltd

·       Lundbeck Foundation

·       Sigrid Jusélius Foundation

·       Parkinson’s UK (innovation Grant)

·       Academy of Finland Project Grants

·       Centre of Excellence in Molecular Cell Engineering

·       Estonian Research Council

·       Finnish Parkinson’s Foundation Fellowship

·       Finnish Funding Agency for Innovation

·       Yulia A Sidorova, CSO GeneCode Ltd

·       Mart Saarma 

Centre of Excellence in Molecular and Integrated Neuroscience at the Institute of Biotechnology, University of Helsinki

This group led the research and can be considered on the forefront of research combining seven internationally recognized groups to work on the structure and function of neuronal growth factors and their targets in brain development, neuronal signaling and basic mechanisms of disease. These teams collaborate at the Viikki Campus of the University of Helsinki and bring to the table a wide variety of complementary expertise in critical fields from molecular and cellular neurobiology to neurophysiology and systems neuroscience.

Lead Research/Investigators

Lead researcher Mart Saarma, PhD, is an academy professor and director of the Centre of Excellence in Molecular and Integrated Neuroscience at the Institute of Biotechnology, University of Helsinki. He focuses on the role of neurotropic factors in development and neurodegenerative diseases. His group has characterized several new GDNF family receptors and demonstrated that RET receptor tyrosine kinase is the signaling receptor for GDNF. He has received several domestic and international science prizes for his team’s work including the Nordic Science Prize by Lundbeck Foundation in 2009.

·       Mart Saarma, PhD (corresponding author)

·       Maxim M. Bespalov, PhD 

·       Mati Karleson, PhD 

·       Arun Kumar Mahato, MSc 

·       Jaakko Kopra, PhD

For the rest, see source.

Patents

These University of Helsinki researchers have been getting down to business filing patents—note that Maxim M. Bespalov, PhD, Mati Karleson, PhD, and Mart Saarma, PhD are inventors in composition of matter patents of BT Compounds US Patent No. 8,901,129 B2 and European Patent No. 2509953 while Mati Karleson, PhD and Mart Saarma, PhD are inventors in patent application WO 2014041179 A1 on the treatment of peripheral neuropathy using GDNF family receptor alpha 3 (GFRα3) type receptor agonists.

Call to Action: Interested in connecting with these researchers—exploring future commercial opportunity. Perhaps connect with Dr. Saarma