Blood-Based Biomarker for Alzheimer's Disease

NanoSomiX has the exclusive rights to a newly developed breakthrough technology, based on a recently published study by Goetzl,, which measures a key protein associated with the development of Alzheimer's disease (AD). The introduction of a predictive, reliable and cost-effective screening blood test for early AD is expected to have a significant impact on research into drug development and patient management.

Alzheimer's Disease

Alzheimer's disease (AD) is the most common type of dementia affecting individuals 65 years and older, and is the sixth-leading cause of death in the U.S. It's estimated that 5.2 million Americans of all ages have AD, and because this condition is underdiagnosed, an estimated 50% of these individuals may not know they have this disease. As the nation's population continues age, by 2050 the number of Americans with AD may almost triple, to 13.8 million.

Scientists now know that changes in the brain begin many years prior to the onset of AD symptoms such as memory loss. Abnormalities such as protein accumulation (plaques) and nerve cell damage (tangled nerve cells) may start to appear more than 20 years before cognitive decline is diagnosed. Recent research indicates that AD pathology develops in a staggered sequence, with plaques comprised of amyloid-β protein starting to develop very early in the disease pathology and neurofibrillary tangles following, accelerating before symptoms emerge.

Disease Progression

The National Institute of Aging and the Alzheimer's Association guidelines recognize this continuum of disease progression and identify three stages of AD. The earliest stage is Preclinical AD, which is characterized by detectable changes in the brain, spinal fluid and blood, but cognitive symptoms have not yet developed. The next stage is Mild Cognitive Impairment (MCI) due to AD, where patients exhibit mild, measureable changes in cognitive abilities but these changes do not affect their ability to perform daily activities. The final stage is Dementia due to AD, where the symptoms are obvious and affect the ability of an individual to function in daily life.

The damage that has been done by the final stage of the disease appears to be irreversible. So researchers and drug companies are focusing on gaining a better understanding of the two earlier stages where intervention may have a greater impact in slowing or even reversing disease progression. A major challenge, however, is to identify patients in these earlier stages.

Biomarkers for Alzheimer's Disease

A rapidly growing area of interest is in identifying biomarkers for AD. Biomarkers have the potential to detect changes in the brain many years prior to the onset of symptoms and may provide anatomical evidence to help in characterizing the stage of disease. It's also anticipated that biomarkers will be critical in:

* Monitoring treatment effects and outcomes;

* Helping to define appropriate therapy regimens, and

* Pre-selecting, for inclusion in clinical trials, individuals who are clinically normal but have a high risk of developing AD.

Eventually, biomarkers will also be used in clinical practice to diagnosis and predict future disease risk.

Two leading biomarker candidates, beta amyloid and tau, are of particular interest because they are directly involved in the brain abnormalities associated with AD. Studies indicate that the accumulations of these two proteins together in the brain are associated with neuronal injury: beta amyloid accumulates outside of the neurons to create plaques and an abnormal form of the tau protein accumulates inside the neurons creating tangles.

Cerebrospinal fluid (CSF) levels of both beta amyloid and tau are substantially altered very early in the disease progression. In particular, multiple studies have shown that CSF tau is tightly correlated with the neuronal injury associated with AD. The detection of tau through the collection of CSF, however, is an expensive and painful process for the patient.

Because tau protein is so closely aligned with the onset of AD, alternative methods for detecting changes in tau protein levels is highly desirable. Potential imaging techniques currently under investigation to detect tau accumulation, however, will be expensive and not readily accessible to everyone. One of the most highly desirable approaches, using a blood-based assay to detect changes in tau, has not been feasible until now.

Breakthrough in Tau Detection in Blood

The form of tau protein that is associated with AD and detected in CSF is phosphorylated-tau (“p-tau”). Once p-tau crosses the blood/brain barrier and enters the blood stream, however, it's no longer directly detectable because exposure to enzymes changes the structure of the protein.

To overcome this problem, NanoSomiX is offering an innovative, proprietary method based on the work of Dr. Goetzl to detect p-tau in the blood via exosomes. Also known as extracellular vesicles, ectosomes and nanosomes, exosomes are tiny membrane-encased vesicles that are excreted from cells. They are present in a variety of biological fluids including blood, CSF and urine.

Prior to this study, neuronal exosomes were known to exist in CSF, but had never been detected in blood. Dr. Goetzl's research identified the unique signature for neuronal exosomes, and developed an assay for their detection and isolation in blood. It is now estimated that around 10% of exosomes in the blood originate from the nervous system.

Once the exosomes are excreted into the circulating bloodstream, the exosome membrane protects the proteins encapsulated inside, preventing exposure to enzymes that can alter their structure. In the case of p-tau, for example, exosomes preserve the phosphorylation structure of the protein.

Availability of Blood-Based Assay

NanoSomiX is in the process of commercializing the only blood-based assay for the measurement of p-tau. This process uses a proprietary method to detect and isolate neuronal exosomes from blood plasma. Newly published data shows that the assay can detect p-tau up to 10 years prior to diagnosis of AD and can differentiate between normal cognitive controls, AD and frontotemporal dementia.

The NanoSomiX p-tau blood test will be available in the fall of 2014 for researchers and pharmaceutical companies that are currently using, or would like to use, p-tau as a biomarker for drug evaluation and/or patient sample enrichment in clinical trials. All testing is performed in a federally regulated clinical laboratory (known as an approved CLIA laboratory).

NanoSomiX has multiple patents pending on the method of sample preparation and assay process. The process is automatable and expandable to other disease states. NanoSomiX is interested in collaborating or partnering with interested parties to generate additional data.