Back in July we reported that the Bill Gates had launched a new fund to support Alzheimer’s research called Diagnostic Accelerator. The project is a part of the Alzheimer’s Drug Discovery Foundation (ADDF) aims to accelerate bold new ideas for earlier and better diagnosis of the disease. This is important for will contests, since an accurate diagnosis sometimes forms the basis of litigation in challenging a will.
We thought it might be beneficial to do a deep dive on what exactly biomarkers are and explore where they have been beneficial in healthcare and why they are lacking in Alzheimer’s research. We will also show how the evolution of biomarkers in Alzheimer’s diagnosis could be a real game changer for how the disease is treated and potential for better outcomes.
As the sixth leading cause of death in the U.S., Alzheimer’s is the only one that can’t be prevented or even slowed. We currently have diagnostic tools to easily diagnose cancer and heart disease. And in the event of diagnosis, we have medications to treat the conditions. But despite considerable funding and hours of research, no new treatments have been approved to treat Alzheimer’s disease in the last 16 years. Let that sink in. In 16 years no breakthroughs have been significant enough to warrant an FDA approved treatment. Meanwhile, the number of individuals diagnosed with the disease climbs and is projected to do so into the foreseeable future.
Some say the reason there hasn’t been any progress is the research is because the emphasis has been on drugs targeting beta-amyloid proteins, the proteins that clump together to form the plaques in the brains of affected individuals, the root cause of Alzheimer’s. Now there has been a clarion call to shift the research to discovering an affordable option for diagnosis.
As Gates pointed out in launching his initiative, there is an absence of affordable and noninvasive biomarkers that can be effortlessly implemented in doctors’ offices.
These simple and inexpensive tests are one of the key things missing from Alzheimer’s diagnosis. Currently, many other diseases, such as diabetes, hypertension and cancer have these tools readily available that make immediate treatment — and specific treatments targeted to each individual case — readily available. For example, in the case of heart disease, measuring serum cholesterol levels has been used as a biomarker to identify patients at risk. This blood test is simple and affordable and if cholesterol levels prove to be elevated, drugs like statins can immediately be prescribed to lower it. Doctors are further able to continue testing levels to identify if medications are working and make necessary adjustments with dosage to ensure success. Furthermore, since the FDA recognizes blood cholesterol as a surrogate biomarker, clinical trials can simply show a drug lowers cholesterol and get approval, thus advancing heart disease research and treatment options.
Currently diagnostic and prognostic biomarkers such as PET brain amyloid imaging and CSF based amyloid and tau tests are currently clinically available for Alzheimer’s disease, but only 5 percent of patients in the U.S. have been tested with these confirmatory clinical biomarkers because of the prohibitive cost and access restrictions. And payers (i.e, insurance companies), including the Centers for Medicare & Medicaid Services (CMS), won’t cover these tests based on the perception that a definitive diagnosis has little clinical value.
However, biomarkers to specific molecular targets can be used to predict the likelihood a person will develop Alzheimer’s disease (such as the currently available blood tests for apolipoprotein E genotyping) and provide a diagnosis even before symptoms are noticeable (such as the currently available positron emission tomography [PET] amyloid scans and cerebral spinal fluid [CSF] tests). Biomarkers can also be employed to enroll patients in clinical trials directed to a specific target, like beta-amyloid, and measure how the body responds to a treatment, as was done most recently by Biogen with its anti-beta amyloid vaccines. Consequently, biomarkers can ascertain which therapies would be most effective for an individual.
In March of this year the FDA issued guidelines acknowledging the crucial role of biomarkers in illustrating efficacy (especially in early the stage) in clinical trials for Alzheimer’s disease. We will explore these guidelines in a future post. These new guidelines help clear a major hurdle in developing drugs to treat Alzheimer’s.
It is now imperative to put our focus on developing inexpensive and noninvasive biomarkers, ideally through simple blood tests conducted in doctors’ offices, that will help diagnose Alzheimer’s disease and track the effectiveness of treatments. This will pave the way for more efficient and rigorous clinical trials and speed up the development of new drugs. Not to be overlooked, the development of these diagnostic biomarkers will greatly improve clinical care and make it possible to assess more accurately which treatment and prevention strategy is best for each individual suffering from Alzheimer’s disease or other dementia related diseases.
We haven’t always had tests readily available to us that easily diagnose cancer, heart disease and other chronic age-related diseases. With concentrated focus on development of novel biomarkers its hopeful that targeted treatments of these diseases are not far away. You can read more about biomarkers in the book “Biomarkers in Alzheimer’s Disease” by Tapan Khan.