A Ticking Timebomb: The Need to Invest in Research on Neurodegenerative Disease

February 15, 2018

Last month, Pfizer announced plans to end its new drug research efforts for Alzheimer's and Parkinson's diseasesa devastating blow for those seeking therapeutic developments for neurodegenerative disease. Cara Altimus, associate director of the Center for Strategic Philanthropy, appeared on Al Jazeera NewsGrid to speak about the unfortunate implications of this decision, and how to effect change in a positive direction.

 cara Al Jazeera

Cara Altimus, Associate Director of the Center for Strategic Philanthropy, on Al Jazeera NewsGrid.

Sadly, there is a certain inherent logic to this decision, given the dismal clinical trial success rate of 0.4% for these treatments (compared to 19% for cancer). It highlights the need for bolder approaches to a very difficult problem. 

Today, neurodegenerative disease is one of the most costly national health care expenses: the 2017 costs of dementia care were greater than 250 billion dollars. However, over the next 30 years, that number is expected to increase four-fold to reach 1.1 trillion dollars annually, dramatically increasing federal spending through Medicare and out-of-pocket expenses. 

Meanwhile, hundreds of drugs have been tested in clinical trials with abysmally low success rates leaving patients and families with no treatment options. As a global community, we must ask ourselves: Is this is a crisis that we will walk away from?

Decades ago, a cancer diagnosis was a death sentence. Researchers were just beginning to understand that cancer was a broad class of diseases that would require many unique therapeutics, and funders saw the importance of basic research to uncover the cellular mechanisms regulating cancer development. Through nationally coordinated research, innovation, and streamlined clinical trials, we are now able to celebrate a growing range of cancer therapeutics that continue to increase the cancer survival rate.

Why are neurodegenerative diseases different?

When we compare cancer’s trajectory to that of neurodegenerative disease, we see two very different paths.

Alzheimer’s and Parkinson’s disease were first described 100 and 200 years ago respectively, but they were not prioritized until the mid-20th century. Researchers have discovered that both diseases are characterized by clumps of aggregated proteins and the death of brain cells. However, neither the mechanism of death nor the mechanistic link between protein aggregation and disease are understood. Just as cancer was found to be a broad classification of many different diseases, scientists are discovering that Alzheimer’s disease and Parkinson’s disease are not monolithic but are a range of disorders. In order to identify and characterize the spectrum of Parkinson's disease and Alzheimer's disease, researchers have sought new diagnostic tools.

A telling example of the problem is in the Alzheimer’s clinical trials. Alzheimer’s is characterized by the aggregation of a specific protein, amyloid-beta, in regions of the brain important for memory. As such, many drugs have targeted the amyloid protein. However, in a recent study of clinical trial patients, one third of the Alzheimer’s treated group did not have amyloid protein deposits in their brain, while one third of the control patients who were not diagnosed with Alzheimer’s disease did have amyloid deposits--highlighting both our difficulty in defining the disease, as well as in assigning consistent diagnoses.

What do we do?

Similar to the cancer field decades ago, we need to understand the spectrum of diseases that lead to neurodegeneration. That means elucidating the underlying biology which leads the brain cells to die. Without this basic understanding, drug trials are shots in the dark.

Furthermore, we need definitive tests to accurately diagnose the diseases which will lead to more successful clinical trials and improve the care of individuals who develop the neurodegenerative disease. The size and complexity of the effort to understand and treat cancer contains an important lesson for the AD/PD communitypartnership and public investment are absolutely essential.

In 1971, President Nixon spoke about the Nation’s “War on Cancer” and signed legislation which provided additional funding and authority to the National Cancer Institute. Additionally, private foundations, such as the Prostate Cancer Fund and Melanoma Research Alliance, have aggressively funded the space, facilitating the successful translation of basic science discoveries into marketable therapeutics. Partnerships were formed between federal, non-profit, and private entities to streamline clinical trials. These are the types of activities that the country will need to undertake if we want to take on neurodegenerative disease. 

What’s already being done?

In 2016 and 2017, Congress approved a 400 million dollar increase in Alzheimer’s spending. In 2017, Bill and Melinda Gates also announced that they were investing their own philanthropic dollars in Alzheimer’s research.

While these are certainly huge steps forward, we have to ask ourselves if this is enough. Are our efforts coordinated? Are we taking the appropriate steps to understand the basic biology of the diseases or building tools to diagnose people? Is there a pipeline in place that moves promising discoveries from the lab, through translational and pre-clinical stages, and into the clinic? Is there a robust clinical trial infrastructure to streamline drug trials or ensure we test the appropriate drugs on the best patients?

Right now, the answer to these questions is a resounding “no.” However, as we continue to understand the magnitude of the crisis, these are also places where federal, philanthropic, and nonprofit funders can make a great impact. As these other sources of research funding continue to drive our understanding of neurodegeneration, they will entice risk-averse pharmaceutical companies like Pfizer to continue drug development for dementia.