AADC Activity Can Be Assessed with High Resolution FMT-PET, Study Shows

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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AADC deficiency and gene therapy

Changes in the activity of the enzyme aromatic l-amino acid decarboxylase (AADC) can be assessed through a high-resolution imaging technology called FMT-PET, a new study has confirmed.

The study also showed that measuring changes in AADC activity in the brain by FMT-PET — an abbreviation for 6-fluoro-meta-tyrosine positron emission tomography — could help identify people with rapid eye movement (REM) sleep behavior disorder who are more likely to progress to Parkinson’s disease or related neurological disorders.

The study, “Longitudinal study of striatal aromatic l-amino acid decarboxylase activity in patients with idiopathic rapid eye movement sleep behavior disorder,” was published in the journal Sleep Medicine.

AADC is critical for the production of certain neurotransmitters, which are chemicals that neurons use to communicate. Specifically, AADC is needed for the production of dopamine, and several neurological disorders are characterized by an abnormal function or loss of dopamine-producing neurons. That is why measuring the activity of AADC might offer insights about disease progression.

REM sleep behavior disorder (RBD) is a condition in which a person acts out actions taken during dreams. Sleep disorders like RBD are common among people with Parkinson’s. Apart from Parkinson’s, previous research has indicated that people with RBD also are more likely to develop neurological disorders such as dementia with Lewy bodies and multiple system atrophy (MSA).

However, not all people with RBD will develop these neurological conditions. As such, there is an ongoing need for ways to determine which people with RBD are most likely to develop neurological disorders, so these individuals can receive appropriate care.

Researchers in Japan tried to identify predictors of neurodegeneration of dopaminergic neurons in RBD patients.

The research team used FMT-PET to measure the activity of the AADC enzyme. This method has been used before to evaluate the effectiveness of an experimental gene therapy for AADC deficiency. (In this case, the gene therapy increased the levels of AADC enzyme in children.)

In total, the study reports data from 24 people with RBD (average age at baseline of 65.4 years) who underwent two FMT-PET scans (at baseline and follow-up). Participants were regularly assessed by neurologists for any sign of neurological disease, and were referred for additional testing if there were suspicious results.

As of the end of the study (in 2019), six of the study participants had developed Parkinson’s, and five had developed dementia with Lewy bodies (one case with parkinsonism). On average, these conditions were diagnosed 4.8 years after the second FMT-PET scan.

The remaining 13 participants showed no signs of parkinsonism or dementia at the end of the study, an average of 6.4 years after the second scan.

There were no obvious differences in FMT-PET readings at the baseline scan. However, individuals who progressed to develop neurological disorders had significantly lower scores on the second scan; that was evidence that AADC activity was decreasing over time in this group. This pattern was consistent across multiple regions of the brain.

“These results clarified that the process of dopamine synthesis in dopaminergic nerve terminals changed over time and suggest that FMT-PET may predict the risk of developing neurodegenerative diseases in patients with [RBD],” the researchers wrote.

Based on the results, a single baseline FMT-PET measurement is not as good at predicting disease progression as changes in this metric over time, the team noted. Multiple FMT-PED scans during a short-term follow-up period could therefore be useful in assessing a RBD patient’s risk for neurological disorders.

Importantly, according to the researchers, this technology also could have applications for measuring whether investigational treatments are working, as previously shown in patients with AADC deficiency.

“These findings provided further evidence of the utility of measuring changes in AADC activity using high resolution FMT-PET as an objective, more sensitive biomarker for investigating the effects of novel, short-term interventions,” the researchers wrote.