Duration: 04/15/2020 - 04/15/2022

Abstract:

Alzheimer's disease (AD) is a hard process for patients, caregivers, and a threat to national health systems. It represents 60-80% of the 46.8 million cases of dementia worldwide. Diagnosed in advanced stages, early detection is essential to prevent severe damage of the brain, and to demonstrate new AD drug's efficacy in clinical trials. ADmit is the first IVD test for the early detection of AD even in the absence of signs of dementia. ADmit is protected by patent. Our main competitive advantage is the early detection of AD before the appearance of cerebral abnormal protein aggregates using a non-invasive technique. The test measures a pool of mitochondrial biomarkers in blood samples using next generation sequencing techniques.

Duration: 03/13/2020 - 03/13/2021

Abstract:

Alzheimer’s disease is the most common form of dementia, affecting approximately 5.8M people in the U.S. It is estimated that without effective therapies, the burden of this disease is predicted to increase from $172 billion in 2010 to a trillion dollars by 2050.

One of the critical challenges in developing therapies against Alzheimer’s disease is the lack of non-invasive objective blood-based tests for proteins associated with Alzheimer’s, called biomarkers. Today, detection these biomarkers requires lumbar puncture, a highly invasive and risky procedure, to collect cerebrospinal fluid (CSF) as a sample. Recently, it was discovered that the same proteins found in CSF could also be found on exosomes, which are small biovesicles that serve as messengers in cell-to-cell communications in the body. Once released by brain cells, exosomes cross the blood-brain barrier, disseminating into many biofluids, including CSF and blood.

Existing methods of analysis of the exosomes require laborious multistep workflows and expensive equipment, which prevents them from being commercially viable for high-throughput applications, such as drug development.

The Verita platform, developed by Biological Dynamics, enables a fully automated single-step on-chip capture and analysis of proteins on the surface of exosomes.  It has the potential to become the first platform to offer standardized testing for Alzheimer’s biomarkers at a high throughput.

This proposal outlines key activities needed to design a multi-biomarker testing panel for the detection of 10 of the most promising, to date, Alzheimer’s biomarkers on exosomes.  The panels will be evaluated on how well they detect the biomarkers of interest as well as on feasibility for use in commercial drug development for patient selection, the measurement of the intended effects of drugs, and the provision of evidence on the effectiveness of therapies.

Duration: 12/20/2019 - 12/20/2021

Abstract:

Alzheimer’s Disease is a terrifying illness that progressively destroys thinking and memory skills,embodying one of the greatest fears for people over the age of 60. Unfortunately, drug companies havefailed to discover medicines which are effective against Alzheimer’s. One reason for this is that oncepeople start to experience problems, nerve cells are already dead and cannot be brought back. However,there is hope: if we step in early, we have a bigger chance of slowing and possibly reversing theprogression of disease. This requires detecting the earliest signs of Alzheimer’s in the brain, long beforenerve cells start to die. This can already be done by taking pictures of the brain at a high resolution orthrough a puncture into the spine. However, these procedures are very unpleasant and expensive so thatthey are not suitable for the many people at risk. Fortunately, although the brain is partially separatedfrom the rest of the body through the so-called blood brain barrier, it is in constant conversation withthe blood system. Therefore, we want to take advantage of this crosstalk and use a simple, inexpensiveand minimally-invasive blood test to find out if Alzheimer’s is developing in the brain. The moleculewe are using for this are called “microRNAs”. They are tiny giants of gene regulation that act asmolecular thermometers reflecting a person’s health status. We propose to use a combination of severalmicroRNAs as biomarkers for the early detection of Alzheimer’s. If we are successful, our approachcould be used as a simple tool for disease screening but also improve the drug discovery process ascompanies would now have a better way to identify patients and evaluate the effects of their drugs beforeit is too late.

Duration: 03/04/2020 - 03/04/2022

Abstract:

A recently proposed new research framework defines patients affected by Alzheimer’s Disease (AD) based on pathological hallmarks, instead of symptoms or signs such as mild cognitive impairment (MCI). This research framework is intended to help guide studies developing potential new treatments for AD. The core of the research framework is to define patients according to the following biomarker levels: amyloid (Aβ), tau, and neurodegeneration status (A/T/N).

Currently, amyloid status can be assessed by imaging amyloid PET or Cerebral Spinal Fluid (CSF) Aβ measurements, both of which are either extremely costly (PET) or require invasive procedures (CSF lumbar puncture). Both of these procedures, and the aspiration to define patients by these criteria, are estimated to result in ~80% patient screen failure rate and contribute to the extremely high costs of clinical trials in Alzheimer’s Disease. Ideally, a much simpler blood-based test for amyloid status would help to simplify clinical trials, reduce patient burden, and reduce the costs required to identify and characterize AD, particularly as clinical research moves into earlier stages of the disease where patients need to be identified in a pre-symptomatic state (no cognitive impairments).

The goal of this project is to perform an independent validation of the top performing blood plasma Aβ assays and determine which are the most robust in terms of having a high degree of correlation with amyloid PET or CSF Aβ levels. The desired outcome is to offer the research community guidance on which assays might help streamline clinical trials and aid in AD diagnosis.

Duration: 03/16/2020 - 03/15/2022

Abstract:

In Alzheimer’s disease, molecules damaged by free radicals can build up and cause toxic damage in the brain. Currently, there are no established ways to measure this process in living patients. Therefore, identifying and developing methods to measure other aspects of the disease are needed. This project will fill this gap by further developing a novel MRI technique to image features of oxidative stress, which causes extensive damage to fats, proteins and DNA in the brains of Alzheimer’s patients. Validating this imaging approach will allow researchers to measure damaging molecules in living human brains and help identify patients for clinical trials of anti-oxidant therapies.