Imaging agent spots TDP-43 clumps in ALS patients in trial

AC Immune’s experimental imaging agent ACI-19626 continues to show a good safety profile and has shown promise for detecting toxic TDP-43 protein clumps in people with amyotrophic lateral sclerosis (ALS).

That’s according to new data from an ongoing Phase 1 clinical trial (NCT06891716), in which the PET tracer was taken up at significantly higher levels in people with ALS than in healthy controls in key brain regions. The findings are consistent with earlier results in people with frontotemporal dementia (FTD), a neurodegenerative disease that, like ALS, is associated with abnormal TDP-43 buildup in the brain.

“These data in ALS patients provide further evidence of ACI-19626’s potential to detect [disease-causing] TDP-43 in the brains of patients with [TDP-43-related diseases],” Andrea Pfeifer, PhD, CEO of AC Immune, said in a company press release.

ACI-19626 also showed a rapid entry into the brain after injection and relatively quick clearance afterward, pharmacological properties suitable for brain imaging and for evaluating of therapies targeting TDP-43-related disease mechanisms, the company said.

The company presented the findings in a talk titled, “Initial clinical characterization of [18F]ACI-19626: the first-in-class TDP-43 PET tracer,” at the 2026 TDP43 Summit, held May 21 in Madison, Wisconsin.

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Tracer designed to bind to clumps, enabling identification

TDP-43 helps regulate gene activity. In most people with ALS, however, the protein misfolds and forms abnormal clumps inside nerve cells. These clumps are believed to emerge early in ALS and to play a key role in driving the disease, which is marked by the progressive loss of nerve cells that control movement.

This has made TDP-43 clumps a promising ALS biomarker. However, there has been no reliable way to directly detect and measure these abnormal protein deposits in the brain and spinal cord of living patients.

PET tracers are radioactive compounds that bind to specific targets in the body. Once injected, they travel through the bloodstream and accumulate in areas where the target is present. PET scans then detect the radioactive signal, allowing researchers to indirectly measure the amount of the target.

AC Immune’s ACI-19626 is a PET tracer designed to bind to abnormal TDP-43 clumps. By enabling doctors to identify those clumps, the tracer could serve as a biomarker to help physicians diagnose ALS earlier and monitor whether therapies targeting TDP-43 are working.

In preclinical studies using patient-derived brain samples, the tracer was found to selectively bind to the abnormal clumped form of TDP-43, but not to the normal TDP-43 protein or clumps formed by other proteins. Studies in monkeys also suggested the tracer had pharmacological properties suited for PET imaging, including rapid brain entry and clearance from the body within hours.

These promising findings supported the launch of the ongoing Phase 1 trial, which is being conducted in two parts. The first part evaluated the tracer in a small group of healthy volunteers and people with FTD to assess its safety and pharmacological properties, including how quickly it reached the brain and was cleared from the body.

Preliminary findings from this part showed that ACI-19626 was safe and well tolerated, and PET scans also showed stronger tracer signals in people with FTD than in healthy volunteers, particularly in brain regions where abnormal TDP-43 buildup is known to occur.

These findings provided early evidence that the tracer could detect TDP-43 clumps in the brains of living patients.

The second part, now underway, will involve up to 30 people with FTD, ALS, or a form of dementia called limbic-predominant age-related TDP-43 encephalopathy. The goal is to further evaluate the tracer’s ability to detect TDP-43 buildup in the brain.

“Early diagnosis is essential for early intervention, and the data generated so far on ACI-19626 further underline the promise of the AC Immune pipeline and our technology to enable a precision medicine approach to multiple neurodegenerative diseases,” Pfeifer said.