Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by the accumulation of α-synuclein in the brain. Now, scientists from Japan, in collaboration with three pharmaceutical companies, have developed a radioligand that facilitates imaging of α-synuclein aggregates in MSA patients. Their findings have the potential to completely change the scenario of diagnosing neurodegenerative diseases.
α-Synuclein is a neuronal protein involved in functions such as vesicle trafficking and neurotransmitter release. It is usually abundant in a healthy brain. However, α-synuclein aggregation has been closely linked to several neurodegenerative disorders, including Parkinson’s disease, multiple system atrophy (or MSA), and Lewy body dementia.
MSA is a movement disorder that also affects the autonomic nervous system, which controls essential functions such as movement, breathing and digestion. Thus, imaging of α-synuclein aggregates in vivo (or directly in a living organism), may be a possible diagnostic confirmation of MSA. However, the path to direct imaging of α-synuclein has been plagued with obstacles, including the lack of sensitive imaging agents.
Now, a collaborative effort of researchers from the National Institute for Quantum Science and Technology, including Drs. Makoto Higuchi and Dr. — Eisai Co., Ltd., Ono Pharmaceutical Co., Ltd., and Takeda Pharmaceutical Company Limited. They have successfully visualized α-synuclein aggregates in the brains of patients. To achieve this feat, the team developed a radioligand, 18F-SPAL-T-06, to be used as a positron emission tomography (PET) probe. “Pre-competitive collaboration between a research institute and three pharmaceutical companies enabled us to develop radioligand, 18F-SPAL-T-06, for in vivo imaging of α-synuclein aggregates,” says Dr. Higuchi, crediting the team’s work for their success. The team’s findings are published in the journal Movement Disorders.
Prior to clinical evaluations, in vitro studies on the binding properties of 18F-SPAL-T-06 was performed on postmortem brain tissue of MSA patients and healthy individuals, showing promising results. For the first-in-human imaging studies, researchers enrolled three patients who were clinically diagnosed with MSA and a 72-year-old healthy control (HC). Among the three patients with MSA, two were identified as having MSA with predominant parkinsonism (MSA-P) and one with MSA with predominant cerebellar ataxia (MSA-C). PET scans with 18F-SPAL-T-06 was performed in all patients and specific binding was assessed by tissue retention of the radioligand. “Surprisingly, we noticed improved 18Uptake of F-SPAL-T-06 in the putamen, pons and cerebellar white matter and peduncles
of MSA-P and MSA-C patients, in sharp contrast to the minimal radio signals in the corresponding areas in the HC brain,” explains Dr Higuchi.
The researchers also found that 18F-SPAL-T-06 has a high affinity for MSA-type α-synuclein aggregates and does not react with other off-target components, indicating its high specificity and potential subsequent use as a probe for the diagnosis of MSA .
Regarding the long-term applications of their work, Dr. Higuchi and Dr. Matsuoka shares, “We are encouraged by our findings, and investigations into the visualization of α-synuclein aggregates in other α-synucleinopathies are currently underway.”