Scientists Develop HANABI Device to Identify Toxic Aggregates in Parkinson’s Patients’ Brains

Joana Carvalho, PhD avatar

by Joana Carvalho, PhD |

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A new test can analyze cerebrospinal fluid samples and help measure how many toxic aggregates of alpha-synuclein can be found in the brains of patients with Parkinson’s disease.

The new assessment strategy was developed by Japanese researchers and was reported in a study, “Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid,” published in Nature Scientific Reports.

Parkinson’s disease is a neurodegenerative disorder mainly resulting from the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for controlling body movements.

Overproduction of the protein alpha-synuclein in nerve cells of the brain, another hallmark of the disease, leads to the formation of small toxic deposits called Lewy bodies that will gradually damage and kill nerve cells. Growing evidence has demonstrated that these alpha-synuclein aggregates are associated with Parkinson’s onset and progression.

A therapy that would be able to prevent the accumulation of these protein aggregates in nerve cells could become a potential treatment for people with Parkinson’s disease.

However, to accurately test the efficacy of such therapies, clinicians must be able to tell how many alpha-synuclein aggregates are present in a patient’s brain before and after treatment. Until now, no specific method assessing the degree of protein accumulation in the brain had been successfully established.

But this may be about to change. A group of researchers from Japan’s Osaka University developed the first strategy that is able to measure the exact amount of alpha-synuclein aggregate buildup in the brain.

The HANdai Amyloid Burst Inducer (HANABI) assay is a fully automated tool that can detect the number of alpha-synuclein aggregates in a patient’s cerebrospinal fluid (CSF) — the liquid that circulates in the brain and spinal cord — using a technique called ultrasonication.

Ultrasonication is a technique in which sound waves are transformed into mechanical disruptive energy. Researchers are able to measure the rate at which alpha-synuclein clumps together to form toxic protein aggregates, a process known as alpha-synuclein seeding activity.

Investigators showed that the seeding activity of alpha-synuclein was higher among 44 patients with a diagnosis of confirmed or probable Parkinson’s disease who participated in a prospective observational study, compared with 17 participants who did not have any neurodegenerative or neuroinflammatory disease.

“This system has the potential to distinguish patients with Parkinson’s disease from controls based on seeding activity of alpha-synuclein aggregates in cerebrospinal fluid,” Hideki Mochizuki, MD, PhD, senior author of the study, said in a news release. “This tells us that the HANABI device is sensitive enough to have real clinical potential, and supports the idea that alpha-synuclein aggregation is a marker of the disease.”

The team also found that the seeding activity of alpha-synuclein in CSF was linked to the uptake of 123I-meta-iodobenzylguanidine (MIBG), a radioactive compound whose low uptake has been linked to neurodegeneration and is considered an important clinical feature of Parkinson’s.

“Therefore, our data, showing a correlation between the HANABI assay and MIBG uptake, suggest that the seeding activity of CSF from patients with Parkinson’s disease could reflect the progression of Lewy body [disease],” researchers said.

Scientists said one of the advantages of using the HANABI assay is the speed at which it can measure alpha-synuclein aggregates in the CSF, surpassing other methods by a large margin.

“The HANABI device was developed to overcome limitations of existing methods and process multiple samples simultaneously,” said Keita Kakuda, lead author of the study. “This has allowed us to drastically shorten the time to perform the assay, from around 10 days to only several hours.”

Further studies are still needed to confirm the clinical relevance of these findings. The team is hoping the new assay might be used to aid clinicians diagnosing, assessing disease severity, and selecting the best course of treatment for patients.