Drug Development

Byoung Hyuck Kim; Keun You Kim; Woo-Yoon Park; Aryun Kim; Eun-Hee Hong; Ji Young Kim; Seong-Jun Cho; Hak Young Rhee; Weon Kuu Chung

doi:10.1002/alz.084076

Drug Development

Alzheimers Dement. 2024 Dec:20 Suppl 6:e084076. doi: 10.1002/alz.084076.

Authors

Byoung Hyuck Kim¹, Keun You Kim¹, Woo-Yoon Park², Aryun Kim², Eun-Hee Hong³, Ji Young Kim³, Seong-Jun Cho³, Hak Young Rhee⁴, Weon Kuu Chung⁴

Affiliations

¹ Seoul Metropolitan Government Seoul National University (SMG-SNU) Boramae Medical Center, Seoul, Korea, Republic of (South).
² Chungbuk National University Hospital, Cheongju-si, Chungcheongbuk-do, Korea, Republic of (South).
³ Korea Hydro & Nuclear Power Co Ltd., Seoul, Korea, Republic of (South).
⁴ Kyunghee University Hospital at Gangdong, Seoul, Korea, Republic of (South).

PMID: 39782493
DOI: 10.1002/alz.084076

Abstract

Background: Recent preclinical studies have revealed a significant reduction in amyloid-β plaques and pro-inflammatory cytokines in Alzheimer's disease (AD) mouse models following low-dose radiation therapy (LDRT). This phase II, multicenter, prospective, single-blinded, randomized controlled trial (NCT05635968, funding from Korea Hydro & Nuclear Power: Grant No. A21IP11) aims to investigate the efficacy and safety of whole-brain LDRT in patients with AD.

Method: Probable AD dementia patients (MMSE 13-24 & CDR 0.5-1) with evidence of amyloid pathology (confirmed by a positive 18F-flutemetamol PET scan) were randomly assigned to one of three groups. They received a total of six fractions of LDRT: Group A with total 0 cGy (sham irradiation), Group B with 24 cGy, and Group C with 300 cGy. The effectiveness of LDRT was assessed through 18F-flutemetamol PET, brain MRI and neurocognitive function tests at baseline, and at 6 and 12 months post-LDRT. The primary endpoint was the change in the ADAS-K-cog score. The secondary endpoints included the changes in 18F-flutemetamol PET, brain MRI, and scores of K-MMSE, CDR, CGA-NPI and K-iADL.

Result: A total of 15 patients (5 in each group) who completed 6 months post-LDRT follow-up were analyzed in this interim analysis. Baseline ADAS-K-cog (mean values in the order of group A, B, and C: 40.8 vs. 30.2 vs. 37.4, p = 0.111), CDR (1.0 vs 0.7 vs. 0.8, p = 0.141), K-MMSE (19.6 vs. 22.4 vs. 19.2, p = 0.125) scores were not statistically different across the three groups. After 6 months, mean differences in cognitive test scores compared to baseline were 3.4 vs. 0.2 vs 0.4 (ADAS-K-cog, p = 0.369), 0.6 vs 0.0 vs 0.0 (CDR, p = 0.089), and -1.8 vs. 0.8 vs. 1.2 (K-MMSE, p = 0.081). Compared to Group A, more subjects in experimental groups (B+C) showed improvement in K-iADL (0/5 in Group A vs. 4/10 in Group B+C) and CGA-NPI (0/5 in Group A vs. 5/10 in Group B+C). LDRT was well-tolerated in all patients without any adverse events.

Conclusion: Whole-brain LDRT for patients with AD was tolerable and demonstrated potential benefits in neurocognitive function tests. Quantitative imaging analysis will follow, and final results with the planned follow-up are awaited.