Brain imaging agent shows promise for detecting toxic ALS protein
Trial data show PET tracer safely detects TDP-43 clumps
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- PET tracer ACI-19626 safely detects toxic TDP-43 protein clumps in the brain.
- TDP-43 clumps are a hallmark in 97% of ALS cases and about half of FTD cases.
- This tracer could aid early diagnosis and monitor treatment response.
ACI-19626, an experimental imaging agent developed by AC Immune, may safely detect abnormal clumps of the protein TDP-43 in the brain, a hallmark of amyotrophic lateral sclerosis (ALS) and other neurological conditions.
That’s according to early data from a Phase 1 clinical trial (NCT06891716) evaluating the safety and pharmacological properties of ACI-19626 in healthy volunteers and people with TDP-43-related diseases. Researchers also aim to assess whether the tracer can reliably measure abnormal TDP-43 buildup in the brain.
Initial imaging findings from the first part of the trial, which enrolled healthy volunteers and people with frontotemporal dementia (FTD), were shared in an oral presentation titled, “Initial clinical characterization of [18F]ACI-19626: the first-in-class TDP-43 PET tracer,” at the International Conference on Alzheimer’s and Parkinson’s Disease (AD/PD), held March 17-21 in Copenhagen.
According to the company, ACI-19626 demonstrated good safety and tolerability and achieved significantly higher levels in key brain regions in FTD patients than in healthy people. The early data support ACI-19626’s potential as a diagnostic tool in people with TDP-43-related diseases.
“These first-in-human data presented at AD/PD are very encouraging and indicate that ACI-19626 could have an important role in early diagnosis of multiple neurogenerative diseases, with a clear path to precision medicine,” Andrea Pfeifer, PhD, CEO at AC Immune, said in a company press release.
Biomarker difficult to detect
TDP-43 normally helps regulate gene activity, but it often misfolds and forms toxic clumps in nerve cells in people with certain neurological diseases.
Abnormal TDP-43 buildup occurs in about 97% of people with ALS and in about half of those with FTD. While this makes it a promising disease biomarker for TDP-43-related diseases, there has been no reliable way to accurately detect abnormal TDP-43 clumps in a living person’s brain and spinal cord.
AC Immune’s ACI-19626 is a PET tracer developed to detect abnormal clumps of TDP-43, with the potential to aid in diagnosing TDP-43-related diseases and monitoring treatment response.
PET tracers are radioactive compounds that bind to specific targets in the body and emit signals detectable by PET scans. Once injected into the bloodstream, the tracer accumulates in areas where its target is present, allowing doctors to indirectly measure the amount and distribution of that target. ACI-19626 is designed to bind to abnormal clumps of TDP-43.
In preclinical studies using patient-derived brain samples, the tracer showed strong binding to the abnormal form of TDP-43, but not to the normal form of the protein or to aggregates of other proteins.
Based on the promising preclinical findings, AC Immune launched the Phase 1 trial, which is actively recruiting participants at a site in the Netherlands.
The study is being conducted in three parts. The first part is evaluating the tracer in a small number of healthy volunteers and people with FTD to assess its safety and its behavior in the body, including how quickly it reaches the brain and is cleared.
The now-ongoing second part expands the study to include up to 25 people with TDP-43-related diseases, including ALS, as well as additional healthy volunteers. The goal is to further evaluate the tracer’s ability to detect TDP-43 buildup in the brain.
A third part will assess test-retest reliability — that is, how consistent the imaging results are over time — by repeating scans in up to five participants from the previous parts within about one month of the first scan.
Early data the company presented showed that PET scans using ACI-19626 detected higher tracer uptake, meaning a stronger signal, in people with FTD relative to healthy individuals. The higher uptake was observed in specific regions of the brain, including deeper (subcortical) and outer (cortical) areas where abnormal TDP-43 buildup is known to occur.
The tracer was also found to be safe and well tolerated, with radiation exposure within accepted limits. It showed rapid uptake into the brain and rapid clearance, indicating it behaves in a manner suitable for brain imaging and could be used to monitor the efficacy of treatments targeting TDP-43-related disease mechanisms.
“We are looking forward to final data from Part 1 of this study, expected in [the first half of] 2026, and have started Part 2 in other patient populations to further define its potential role in this new treatment paradigm,” Pfeifer said.
