Targeting Neuroinflammation in Huntington Disease: Rajeev Kumar, MD

Video

The medical director of the Rocky Mountain Movement Disorders Center talked about the motivations of the phase 2 study on ANX005 for Huntington disease at the 2023 AAN Annual Meeting. [WATCH TIME: 3 minutes]

WATCH TIME: 3 minutes

"Animal models have been studied with transgenic Huntington mouse models showing improvements in neuropathology, with treatments targeting neuroinflammation. Also, knockout models have been done in animal models of Alzheimer disease, showing that reduction in C1q also improves the pathology of those mice models. So, there has been increasing interest in developing specific complement targeted therapies."

Recent research has shown that neuroinflammation plays a critical role in various neurodegenerative diseases, including Huntington disease (HD). Despite no current proven disease-modifying therapies being approved for HD, there has been a growing interest in the field to develop specific targeted complement therapies to address this neuroinflammation.

In a recent analysis, Rajeev Kumar, MD, and colleagues reported the final results of ANX005, a humanized monoclonal antibody designed to inhibit C1q, from a phase 2 trial (NCT04514367) of patients with or at risk of manifesting HD. The findings were presented as an oral presentation at 2023 American Academy of Neurology (AAN) Annual Meeting, April 22-27, in Boston, Massachusetts by Kumar, who served as lead author and is the medical director of the Rocky Mountain Movement Disorders Center.1

In the study, participants with a CAG-Age-Product (CAP) score greater than 400 received intravenous ANX005 every 2 weeks through week 22. The end points were assessed on-treatment through week 24 and off-treatment follow-up through week 36. Kumar and colleagues concluded that ANX005 was generally well-tolerated, and maintained full target engagement, showing clinical improvement in a subgroup of patients with HD.

At the AAN Annual Meeting, Kumar sat down with NeurologyLive® in an interview to discuss the role of neuroinflammation in neurodegenerative diseases such as HD. He also spoke about how targeting the complement cascade, specifically C1q, helps in reducing neuroinflammation in neurodegenerative diseases. In addition, Kumar talked about the patients that were enrolled in the phase 2 trial with ANX005.

Click here for more coverage from AAN 2023.

REFERENCES
1. Kumar, R, Claassen D, Mongan A, et al. A Phase 2 Open-Label Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Intravenous ANX005 in Patients with, or at Risk of, Manifest Huntington’s Disease (HD). Presented at: 2023 AAN Annual Meeting; April 22-27, Boston, Massachusetts.
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