cardiovascular disease

Atherosclerosis is the buildup of fats and other substances in and on the artery walls called plaque. The accumulation of plaque over time can cause arteries to narrow, restricting blood flow. These plaques can also burst, leading to blood clot formation and risk of heart attack and stroke. Even though ASCVD is often considered a heart problem, with plaque development in the coronary arteries termed coronary artery disease  (CAD),  it can affect arteries anywhere in the body. 

With symptoms only arising once a significant blood flow-blockage of blood flow has already occurred.  This has resulted in ASCVD becoming a leading cause of morbidity and mortality worldwide by affecting more than 500 million individuals globally and accounting for 19 million deaths annually.  Here in the United States, ASCVD afflicts about 26 million people and is responsible for 2 million hospitalizations and 400,000 deaths every year.

Current disease treatment approaches focus on reducing approaches to disease treatment of low-density lipoprotein cholesterol (LDL-C) blood levels.  There is a broad list of approved LDL-C lowering medications currently available. However, ~50% of patients who suffer a heart attack have normal LDL-C levels.  This therapeutic paradox is now readily recognized in the research community, and investigational interest is now in exploring LDL particles (LDL-P) rather than LDL-C.  A key LDL-P in the development of ASCVD is the small dense LDL (sdLDL).  High atherogenic in nature, current diagnostic approaches do not account for LDL-P characterization, nor are there any therapeutics to specifically address the sdLDL issue. 

Both MCI and AD are neurodegenerative diseases that are associated with the loss of memory and cognitive function. MCI is commonly viewed as the early transition from normal aging into dementia. As 50% of patients diagnosed with MCI develop AD within five years, there is a clear pathogenic link between the two diseases.  

Currently, AD affects more than 5 million Americans and is ranked as the sixth leading cause of death in the nation.  The exact causes of AD aren't fully understood. Still, scientists believe that, for most people, it is caused by a combination of lifestyle and environmental factors that affect the brain over time. There are also inheritable components, with the single most significant genetic risk factor being the presence of Apolipoprotein E4 (ApoE4), which can leave patients potentially at a 20-fold greater risk of disease development. AD pathology begins years before the first symptoms and most often starts in the region of the brain that controls memory. The loss of neuronal function and their eventual death spread in a somewhat predictable pattern to other regions of the brain regions, resulting in significant brain shrinkage by the later stages of the disease.

1) metabolic function, 2) neuroinflammation, and 3) abnormal neuron protein deposit formation.  To date, the most extensive investigational research has focused on the role of two key proteins: Beta-amyloid in the development of amyloid plaques and tau in the formation of tangles.  Despite recent successes with the approval of Leqembi®, the risk of a serious complication called Amyloid Related Imaging Abnormalities (ARIA) limits the current risk-reward of this treatment.  The risks associated with ARIA are even more pronounced in patients with the ApoE4 gene, resulting in a black box warning and exclusion from use.  This leaves the highest-risk patient group currently without any therapeutic option.