Clinical diagnosis of synucleinopathies like parkinson disease

New family of alpha-synuclein ligands for synucleinopathies PET imaging. Parkinson’s disease (PD), Multiple System Atrophy (MSA) and Dementia with Lewy Bodies (DLB) are devastating synucleinopathies. As of today, The deposition of filamentous insoluble protein inclusions termed Lewy bodies and Lewy neurites whose main constituent is aggregated into alpha-synuclein (α -syn) and characterizes synucleinopathies. PD diagnosis certainty is histological and can not be done during the lifetime of the patient. Diagnosis of PD is thus based on the existence of clinical signs. An early disease and stratification reliable diagnostic test is urgently needed ! Described here is a new family of chemical compounds that highly bind to α–syn aggregates and can be used to develop synucleinopathie imaging diagnosis tool and especially early detection of Parkinson disease.

Competitive Advantages

Development of highly specific ligands to α–synuclein :

• Numerous ligands and back-up available

• Optimized-synthetic chemistry

• 18F ligands available and suitable for clinical trials

• High affinity to α–syn in a nanomolar range

• High specifity to α–syn against other aggregates likeTau or A-Beta

Development Status

Preclinical POC based on 18F labelled molecules :

• Chemistry:

- Design and synthesis of a huge library of small molecules

- Conversion of the best candidates into F derivatives

- Production of 18F ligands

• α–syn binding studies:

- In vitro testing on post-mortem human brain tissues

- In vivo testing on rats and transgenic mice overexpressing form of human α–syn

• In vivo validation of BBB crossing

• Validation of chemical and plasma stability

Business Opportunities

Imaging / Early Detection / Companion diagnostic :

• 18F labeled tracer for PET enabled synucleinopothies diagnostic

• Early detection of Parkinson Diseases

• Differential diagnosis of PD from other neurological lesions resulting from Tau or A-beta aggregates, e.g. Alzheimer

• Therapeutic follow-up /clinical monitoring for synucleinopathy drugs

• Synucleinopathies progression follow-up