Open label, crossover, pilot study to assess the efficacy and safety of perispinal administration of etanercept (Enbrel®) in combination with nutritional supplements versus nutritional supplements alone in subjects with mild to moderate Alzheimer's disease receiving standard care
Authors: Hirsh Steven , Huber Luke , Stein Richard , Schmid Kira , Swick Andrew , Wand Paul , Brody Mark , Strum Stephen , Joyal Steven V. 
Published: November 2023

Background

While the cause of Alzheimer's disease (AD) remains unknown, evidence suggests it develops due to a complex series of events in the brain that occur over time. Two pathways possibly involved in development of AD are inflammation and oxidative stress. Scientists have linked chronic inflammatory events in the brain with the onset and progression of AD. Oxidative stress has also been implicated in the pathogenesis of a number of neurological disorders including AD. Tumor necrosis factor (TNF‐α), a proinflammatory cytokine, has been suggested to play a role in the pathogenesis of AD. Etanercept, an immunomodulating agent approved by the FDA for the treatment of certain arthritic disorders and plaque psoriasis, binds to TNF and blocks its interaction with cell surface TNF receptors. Open label studies with small numbers of patients have reported etanercept may be beneficial for treating AD, however a recent randomized, placebo‐controlled trial did not show benefit. Several nutrients have been shown to decrease TNF‐α levels, act as antioxidants in the body, or alter amyloid‐beta behavior, which may prove beneficial in AD.

Objectives

To compare the effects of weekly etanercept perispinal injections plus daily oral nutrional supplements versus daily oral nutritional supplements alone on cognitive assessment scores in subjects with AD receiving standard care. Assessment also included short term effects of entanercept plus nutritional supplements in cognitive assessment tests before and two hours after etanercept administration.

Methods

Each treatment was received for six weeks with the two treatment periods separated by a 28‐day washout period during which no study treatment was received. The protocol was amended for the final five subjects who continued taking the nutritional supplements for an additional 12 weeks with a visit at the 6 week interval. Treatment effects were evaluated using scores obtained from the ADAS‐cog, MoCA and MMSE assessment tools.

Results

Statistical analysis was conducted on 10 subjects who completed the trial (five of whom completed the additional 12 weeks of nutritional supplementation) and two subjects who dropped subsequent to completing Period 1. The analysis showed no clear, consistent treatment effect in the cognitive function scores in subjects receiving the perispinal injections of etanercept plus nutritional supplements compared to the nutritional supplement‐only arm of the study. In reviewing the safety parameters, the treatments were well tolerated and changes from baseline for clinical laboratory parameters, vital signs, and body weight were minimal.

Conclusion

The treatments demonstrated no clear, consistent benefits in cognitive function in subjects receiving the perispinal injections of etanercept with nutritional supplements compared to the nutritional supplements‐only group. The study medication was well tolerated in individuals with mild to moderate AD.

Support or Funding Information

Supported by Life Extension Foundation, Inc