Novel Neuropeptide Combination Therapy for Treating Alzheimer’s Disease

Background

According to the 2024 Alzheimer’s Disease Facts and Figures, Alzheimer’s disease (AD) is the most common cause of dementia, accounting for 60-80% of cases in the United States. As of 2024, about 6.9 million Americans aged >65 years old are living with Alzheimer’s disease, of which 4.2 million are women and 2.7 million are men. It’s estimated that by 2040, ~11.2 million Americans will suffer from the condition.

Consistent with these epidemiological estimations, the global Alzheimer’s disease therapeutics market size is expected to expand significantly by 2033. Currently, there is no method to prevent or cure Alzheimer’s disease. Altogether, this highlights the significant unmet need to cure Alzheimer’s disease and dementia in general.

Technology Overview

Einstein researcher, Dr. Dongsheng Cai, in his quest to understand neurological changes associated with aging in the brain, discovered that the expression of neuropeptide oxytocin (OXT) and gonadotropin-releasing hormone (GnRH) were markedly reduced in aged-wildtype and 5xFAD mouse model of AD compared to their respective young or age-matched wildtype counterparts. The present study for the first time demonstrated that OXT signaling and GnRH signaling formed an integrated network, one depending on the other, suggesting that these two neuropeptides are necessary to work together for brain health. This significant finding led to the development of the novel OXT-GnRH neuropeptide combination therapy to treat AD.

In proof-of-concept studies, the team has shown that this new OXT-GnRH combination therapy was highly effective at reversing the severe motor and cognitive symptoms of AD in the 5xFAD mouse model (at 9 months old) compared to each peptide alone. Congruent to the improvement of neurobehavioral parameters, OXT-GnRH combination therapy drastically reduced amyloid β plaques in the brain of the 5xFAD mouse compared to monotherapy treatments ().

It is important to note that the 5xFAD mouse model is one of the most well-characterized disease models of AD. It should also be noted that both neuropeptides are already individually in clinical practice for reproductive issues and some other diseases such as cancers, thus warranting the safety for patient applications. The proposed combination therapy, founded on aging research and characterized by one of the most severe disease models of AD, offers promising prospects for patients suffering from Alzheimer’s or other dementia-related conditions unresponsive to current therapies.

Further Details:

• Usmani et al. Nat. Commun. 2024.

Stage of Development:

• In vivo work completed
• Proof-of-concept was completed using the 5xFAD disease model of AD

Benefits

• Targets a network of two neuropeptides related to aging and AD
• Proof-of-concept was developed using the 5xFAD disease model of AD.
• Effective at reversing motor and cognitive parameters associated with AD.
• New peptide-based strategy that reduces amyloid β plaques.
• End products could be peptides or analogs.
• OXT and GnRH therapies are routinely used in the clinics to treat other conditions and are well tolerated in patients.
• Potential to be delivered via nasal administration.

Applications

• Potential treatment for Alzheimer’s disease (AD).
• Potential treatment for other dementia-causing diseases.
• Combination therapy with current anti-amyloid β antibody therapies to treat AD.
• Combination therapy with current therapies to treat the symptoms of AD.

Opportunity

• Licensing
• Collaboration
• Sponsored research