Drug Discovery

Determine which existing drugs or novel chemical compounds most safely and effectively disrupt the Alzheimer’s pathology generated by the highest priority genes.

Three Studies of ACAT Inhibitors as Potential Therapies for AD

Funding year(s): 
2004 to 2010
Funding to date: 
$300,000

It is known that high cholesterol is associated with cardiovascular disease. Cholesterol also regulates the production of the toxic amyloid beta (Aβ) peptide in Alzheimer’s disease (AD). Therapies already developed or in development for dyslipidemia and atherosclerosis are becoming attractive for reducing Aβ in the brains of patients affected by AD. We have previously reported that drugs specifically targeting one step of the cholesterol pathway, acyl-coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, reduced generation of toxic Aβ peptide in cells and an animal model of AD. While currently not marketed, ACAT inhibitors are available for testing in animal models and clinical trials against AD. Our work in these studies, including the design and development of novel ACAT inhibitors, should result in one or more novel ACAT inhibitors with the potential to prevent and treat AD.

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Curcumin Collaborative Project

Funding year(s): 
2010
Funding to date: 
$400,000

This collaborative project will identify and characterize novel curcumin-like derivatives for the treatment and prevention of Alzheimer’s disease. The purpose of the study is to develop means of overcoming obstacles to rapid breakdown and creating methodologies for precisely delivering curcumin derivatives to appropriate locations within the brain.

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Peek and Treat Approach to Diagnosis, Treatment and Monitoring of AD

Funding year(s): 
2010
Funding to date: 
$40,000

The objective of this project is to develop a nanotechnology platform that can simultaneously be used to diagnose and treat Alzheimer's. The work will explore how to develop multifunctional nanocarriers that contain both an imaging agent and a therpeutic agent and also will improve the binding capabilities of the nanocarrier allowing regulation of the release of therapeutic molecules to amyloid lesions.

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Understanding the Up-Regulation of Neuroserpin in the Alzheimer’s Brain and Isolating a Potential Therapeutic Inhibitor of its Action: Continued

Funding year(s): 
2010 to 2011
Funding to date: 
$100,000

The goal of this project is to determine if there is a strong correlation between Alzheimer’s patients with high neuroserpin and high thyroid hormone levels (for both males and females).

Since our initial proposal in Spring 2010, several papers have appeared making the association between thyroid hormone levels and dementia. Thyroid hormones are associated with poorer cognition in mild cognitive impairment. (Dementia Geriatrics & Cognitive Disorders 30:205-11. Bensenor, IM et al. 2010, Subclinical hyperthyroidism and dementia. BMC Public Health 10:298.)

Interestingly, the latter publication only found a correlation among males. We have not assayed enough samples to see whether there is a gender difference with thyroid hormones and neuroserpin among Alzheimer’s disease males. In contrast, there are publications relating hypothyroidism and Alzheimer’s disease; however, this is not surprising since there are probably a number of insults that may trigger Alzheimer’s disease in different individuals.

Still, if we can establish a strong correlation between those Alzheimer patients with high neuroserpin levels and high thyroid hormone levels, treatment of their hyperthyroidism may be a rapid and effective means to diminish neuroserpin levels. Thus, such treatment may delay the progression and extent of cognitive decline, plaque formation and neuronal death in those individuals.

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