PET Radiotracers for Diagnosis and Patient Stratification of Neurodegenerative Disorders

Small molecules that bind to alpha-synuclein deposition and can be used for PET imagining in patients with synucleinopathies
Problem:
Imaging alpha-synuclein (αS) using noninvasive techniques such as positron emission tomography (PET) can help with the early diagnosis of synucleinopathies. Previous PET radiotracers suffer from low binding affinity and off-target binding to structurally similar proteins, such as amyloid-beta (Ab) and tau. Currently, there is no clear candidate for PET imaging studies in patients with synucleinopathies.
Solution:
Dr. Robert Mach and his team at the Medical School of the University of Pennsylvania have identified different scaffolds that exhibit varying propertied for imaging alpha-synuclein in the brains of patients with Multiple System Atrophy (MSA) and Parkinson's Disease (PD. This is a promising development in the clinical differentiation of MSA and PD patients and the monitoring of therapeutic strategies aimed at reducing alpha synuclein burden in the synucleinopathies.
Advantages:

• High binding affinity for alpha-synuclein: low nanomolar range
• 10-20 fold selectivity vs. tau
• 5-20 fold selectivity vs. amyloid beta
• High brain uptake and rapid washout

Stage of Development:

• Proof of Concept
• Early stage clinical trials

PET radiotracers combining autoradiography enable visualizing the distribution of aggregated α-synuclein in PD and MSA tissues

Intellectual Property:

PCT Filed
Reference Media:

Ferrie, JJ et al. Chem Sci, 2020, 11(37): 12746.
Lee, VMY et al. J. Med. Chem. 2023 Aug, 66(17): 12185.
Desired Partnerships:

• License
• Co-development

Docket# 23-10326