A Spectroscopic Approach to Overcome the Barriers of Early Familial Hypercholesterolemia Diagnosis
Abstract
Critical Problem: Familial hypercholesterolemia (FH) is a common, life-threatening disorder where an individual has significantly elevated bad low-density lipoprotein (LDL) cholesterol. Diagnosing FH at a late stage in life is problematic since, when left untreated, it can result in heart attacks and heart disease at younger ages. The longer an individual experiences high bad cholesterol, the greater their risk for heart attack or stroke. These effects result because sustained exposure of the arteries to elevated bad cholesterol levels accelerate its deposition and can result in premature coronary heart disease (CHD). Knowing both the good (HDL) and bad (LDL) cholesterol levels is extremely important as it allows a person to reduce the risk of heart disease and stroke, the two leading causes of death in the United States, through lifestyle changes and medications. Unfortunately, for individuals with FH, modifications in lifestyle, such as exercising and eating a healthy diet, are insufficient to combat this disease. Medical treatment and medications are necessary, and early treatment can lead to substantial reductions of cardiovascular events and death. The critical problem is that only 10% of the individuals born with FH know they have it and are diagnosed, resulting in an urgent need to improve early diagnosis of FH. While FH can be diagnosed both clinically and genetically, these approaches require either a blood test, which is invasive and does not directly measure LDL but rather is estimated from other measurements, along with family history of elevated bad cholesterol or DNA-based genetic testing, which face significant challenges. Implementation challenges for genetic testing include factors such as availability, cost, concerns about insurance underwriting, and ensuring gender and ethnic diversity across populations screened, among others, which need to be overcome. Overall, health and socioeconomic benefits would result from earlier identification and management of FH. Innovation: Our innovation is to use near infrared light (just outside the visible spectrum) and gold nanorods as a means to measure bad (LDL) cholesterol more accurately and directly. Gold nanorods are tiny particles made of pure metallic gold. They are elongated and rod-like in shape, but only 0.1 microns in length. For perspective, a typical human cell is 10 microns across, and a hair is 100 microns wide. The nanorods therefore diffuse through solution and interact with other molecules, but since they are metallic they strongly scatter the near infrared light, and exactly how they scatter the light depends on the molecules near their surface. Our innovative approach exploits both the optical properties of the gold nanorods and their surface coatings. The nanorods will be coated with phospholipids, which are the fat molecules that make up the thin membrane that surrounds cells. Cholesterol permeates into cell membranes where it plays an important role in the membrane’s molecular structure and function. By disguising the gold nanorods so that they mimic a cell membrane, they will trap and detect the presence of nearby cholesterol. Our technology will be able to tell the difference between LDL (bad) and HDL (good) cholesterol by how quickly the cholesterol jumps onto the nanoparticle surfaces. Cholesterol is detected by looking at the scattering of different colors of light (spectra), which includes cholesterol-specific peaks. Our strategically designed nanoplatform, based on laser light scattering, will enable us to detect and directly measure LDL cholesterol in an individual more easily and effectively, reducing the painful process of obtaining blood and allowing for a more widespread and easily implementable means to directly measure LDL-C for earlier FH diagnosis. Applicability and Impact: The proposed research is submitted under the FY21 PRMRP Topic Area of Familial Hypercholesterolemia. We anticipate that our diagnostic app
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210002
Entities
People
- Carly S Filgueira
Organizations
- Houston Methodist Research Institute
- United States Army