NIH grant: Amyloid clearing therapy in dementia with Lewy bodies plus Alzheimers disease (ACT DLB+) (1U01NS145959-01)

retained text

NIH grant 1U01NS145959-01: Amyloid clearing therapy in dementia with Lewy bodies plus Alzheimers disease (ACT DLB+)
Institute: {'code': 'NS', 'abbreviation': 'NINDS', 'name': 'National Institute of Neurological Disorders and Stroke', 'admin_org_id': '12500053', 'admin_funding_url': ''}. PI: DOUGLAS R GALASKO. Award: $4161896.
Start: 2026-08-01T00:00:00.
ABSTRACT
Dementia with Lewy bodies (DLB) is the second most common dementia after Alzheimer’s disease (AD). AD
pathology co-occurs in over 50% of people with DLB. There are no FDA approved medications for DLB.
Recently, monoclonal antibody treatments have been approved for the treatment of mild AD, but there are no
data on their safety and efficacy in people with concomitant DLB. Though these drugs are available to
providers, any additional benefit or harm to patients with DLB+AD is unknown. Pathology studies have shown
that AD and DLB pathology co-occurrence correlates with higher tau pathology burden and α-Synuclein
pathology, raising the possibility that AD and α-Synuclein pathology in DLB+AD may interact rather than co-
occur as independent pathologies. If true, then anti-amyloid therapy in people with DLB+AD may slow α-
Synuclein seeding and pathology. Conversely, amyloid deposition may be incidental and associated with age.
Thus, there is equipoise about the potential benefits and an urgent need to systematically study amyloid
clearing immunotherapy in DLB+AD.
Our proposal in this U01 application will evaluate the safety and efficacy of donanemab in a phase 2 double
blind placebo controlled clinical trial of 400 participants with DLB+AD (Aims 1-3) with a long-term extension
observational period of 12 months to gather additional clinical, biomarker, and imaging data to share with the
greater scientific community (Aim 4). Because longitudinal data are minimal in this population of biomarker
confirmed DLB+AD, we plan to provide this data for public use and establish a community engagement
research and inclusivity committee and involve people with lived experience of this disease in shaping this
project to enhance participation. By including people representative of the community, the data will enhance
the generalizability of results. Discovering new treatments for DLB, specifically whether donenamab and
possibly other mAbs targeting amyloid therapies are helpful in patients with DLB+AD, will only be possible
because of this unique partnership with our team of experts and Pharma partner. This therapeutic approach, if
successful, will enable a critical step in discovering a new treatment for patients with DLB +AD, where there
currently are none.

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