Leptin has been considered as a novel treatment for Alzheimer?s disease (AD), but we lack adequate evidence of a biological signal indicative of a therapeutic effect in patients with AD. Some concerns are related to side effects, along with uncertainty about dosing. We will therefore perform a pilot study in patients with AD that is sufficient in scope to assess the impact of Leptin on biomarkers selected for their relevance to the mechanism of action of Leptin and the pathobiology of AD. In addition, the study will help clarify tolerability, safety, and feasibility issues relevant for consideration of a larger subsequent trial. The trial may be used as a stepping-stone to a larger and longer multicenter trial in patients with AD or mild cognitive impairment. 45 patients with mild-moderate probable AD and plasma leptin levels of (
Leptin is an endogenous peptide, native to the endocrine system and was first discovered and patented by Dr. Jeffrey Friedman of Rockefeller University in 1994. Leptin supplementation was able to reverse the obesity in the mutant ob/ob mouse (that does not make Leptin) and this raised hopes for an obesity therapy. While the peptide was well tolerated by humans and exhibited an excellent safety profile in clinical trials, it failed to demonstrate efficacy for the targeted condition (obesity) as a monotherapy. Seminal preclinical research, published in December 2004, showed that Leptin augmentation treatment substantially reduced the brain levels of amyloid beta (?Aβ?) in mouse models. More recently, it was shown that Leptin can also decrease phosphorylation of tau. Importantly, circulating Leptin levels decline in most Alzheimer?s disease (AD) patients prior to cognitive deterioration and continue to gradually decline as the disease progresses. Therefore, Neurotez believes that therapy with a recombinant human Leptin product should be beneficial to AD patients, as a modulator of A and phospho-tau and as an insulin sensitizer. The latter may be quite significant, as the majority of AD patients are characterized by hyperinsulinemia or some form of insulin resistance, including type II diabetes.
| Johnston, Jane M; Hu, William T; Fardo, David W et al. (2014) Low plasma leptin in cognitively impaired ADNI subjects: gender differences and diagnostic and therapeutic potential. Curr Alzheimer Res 11:165-74 |
| Johnston, Jane M; Greco, Steven J; Hamzelou, Ashkan et al. (2011) Repositioning leptin as a therapy for Alzheimer's disease. Therapy 8:481-490 |
