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Shifting the Paradigm of ‘Winner Drug Takes All’ for Neurodegenerative Diseases

Power of Ideas
Shifting the Paradigm of ‘Winner Drug Takes All’ for Neurodegenerative Diseases

A dream for many is to live long and to live well. Alzheimer’s, Parkinson’s, and ALS, three diseases of aging, turn this dream into a nightmare.

Age-associated neurodegenerative diseases account for most life-years lost to disability and are the second leading cause of death worldwide. As the global population ages, the prevalence and societal impact of Alzheimer’s, Parkinson’s, and ALS will become ever greater—with annual costs in the US expected to exceed $1 trillion by 2050 for Alzheimer’s alone. While the financial costs are quantifiable, the impact on the person with the disease and on family members caring for their loved one is incalculable.

Currently, treatments for Alzheimer’s, Parkinson’s, and ALS target symptoms but leave the underlying causes of disease unchecked, leading to the inexorable progression of neurodegeneration. Despite valiant efforts for decades and investments of billions, cures for these diseases remain elusive.

Reasons for the current state of treatment for these diseases are many, but two loom large: focus on a single therapeutic target and the “winner take all” business model.

Paradigm shifts in business and policy sectors will ensure that effective treatments ultimately reach patients who need a cure today.

What’s the ‘Germ Theory of Disease’ Got to Do With It?

This theory captured the minds of scientists and the public, with its ability to explain and treat many of the maladies encountered by humans in the 19th century. The germ theory of disease works—and is lifesaving—when there is a single target. It works when the target is a bacteria or virus, and when a single molecule is dysregulated (for example, statins, which target a single enzyme to lower cholesterol levels). Thanks to this single target drug, millions have averted life-threatening disease.

When this theory works, the “single target” therapeutic strategy can be incredibly effective. Its seductive power is understandable. However, with the neurodegenerative diseases of the 21st century, this approach has met its match.

Alzheimer’s disease (AD) serves as a case study for the limits of a single target therapeutic approach. For Alzheimer’s, beta amyloid plaque has been the signature single target. The controversy regarding the outcomes of anti-amyloid antibody clinical trials has been substantial, captured the public’s attention, and highlighted flaws in the “single target” approach.

Targeting beta amyloid plaque removal can modestly slow progression but does not reverse progression of the disease. Waiting in the wings is another single target: neurofibrillary tangles and associated protein, tau. The first clinical outcomes of anti-tau antibody trials failed to provide clinical benefit. Single target strategies for the hallmark pathologies of AD are not the cure many had hoped for.

Multiple Targets That Change with Progression of Disease

Progressive neurodegenerative diseases of aging like Alzheimer’s are complex, have multiple etiologies, and require a coordinated assault across multiple systems. To complicate matters even more, they are a moving target as evidenced by their progressive nature. Adding to this complexity are sex differences and multiple risk factors that can contribute to these diseases.


The complexity of these diseases requires a multiple target strategy that depend on three major advances. First, a portfolio of therapeutics that target the systems of biology affected in the disease. An example is our therapeutic to regenerate the Alzheimer’s brain, which promotes regeneration and energy production while also reducing neuroinflammation. Second, a portfolio of predictive biomarkers. Third, a precision medicine strategy that integrates predictive biomarker profiles with optimal therapeutic combinations.

The Good News

The building blocks for a precision medicine approach exist. A broad portfolio of well characterized Food and Drug Administration-approved drugs to treat the metabolic, bioenergetic, and immune systems exists. Blood-based clinical assessments exist to monitor metabolic and immune system function. Advances in blood-based metabolic and immune profiling are underway that can be coupled with computational strategies to accurately predict the status of the brain to select optimal treatment combinations.

Business of Winning

To achieve curing Alzheimer’s, Parkinson’s, and ALS, the “winner takes all” business model requires a paradigm shift from the single target blockbuster drug to the blockbuster therapeutic portfolio. Paradigm shifts in business and policy sectors across the spectrum of stakeholders will ensure that effective treatments (new and approved drugs, natural molecules) are patent-enabled for business engagement to ultimately reach those patients who need a cure today. We can win this!