[p4–572]: Interim Report of a Phase 2 Pilot Safety and Efficacy Trial of Gm‐csf/leukine® in Mild‐to‐moderate Alzheimer's Disease
Year: 2017
Type: article
Abstract: Rheumatoid arthritis (RA) patients have a reduced risk of developing AD, which was originally hypothesized as attributable to their usage of non-steroidal anti-inflammatory drugs (NSAIDs). However, clinical trials with NSAIDs were unsuccessful in both AD and MCI subjects. We therefore pursued our hypothesis that intrinsic factors within RA pathogenesis itself may underlie the AD protective effect(s). We focused on the innate immune system, tested several protein cytokines upregulated in RA blood, and found that 20 daily injections of 5 ug GM-CSF reduced AD pathology more than 50% and completely reversed the cognitive impairment of transgenic AD mice. Additionally, we found that bone marrow transplant (BMT) patients treated with Leukine(recombinant human GM-CSF) plus recombinant G-CSF to treat leukopenia showed significantly improved cognitivion at six months compared to BMT patients who received G-CSF alone or no treatment. We are conducting a Phase 2 pilot safety and efficacy trial of Leukine in mild-to-moderate AD subjects at 250 ug/m/day SC for 5 days/week for three weeks with follow-up visits at 45 and 90 days. Neurological and neuropsychological assessments are carried out at baseline, at end of treatment, and at follow-up visits. MRIs are performed at baseline and at end of treatment. Interim analyses of 11 subjects treated with Leukine and 9 subjects receiving placebo showed no serious drug-related adverse events, including no evidence of amyloid-related imaging abnormalities (ARIAs), which indicate micro-hemorrhage or vasogenic edema. When comparing measures at the end of treatment to baseline, the mean changes of the MMSE score (Figure 1), Activities of Daily Living, and Delayed Word Recall score showed improvement in the Leukinegroup relative to the placebo group by repeated measures mixed model analysis and/or permutation T-tests (p<0.05). The differences became non-significant by the follow-up visits. These results, although preliminary and based on a very small number of subjects, indicate that completing the three-week trial and initiating our Alzheimer's Association “Part the Cloud”-funded 24-week trial of GM-CSF/ Leukine in subjects with mild-to-moderate AD are warranted. We will report on the progress of both trials and on the effect of Leukine using Amyvid PET imaging to assess amyloid load.
Source: Alzheimer s & Dementia
Authors: Huntington Potter, Jonathan H. Woodcock, Timothy Boyd, Stefan H. Sillau, Brianne M. Bettcher, Joseph Daniels, Kate S. Heffernan, Helen Gray
Institution: University of Colorado Anschutz
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2765728014