To more effectively treat neurodegenerative conditions, we first need diagnostic tools that lend a more complete picture of protein aggregates in the brain.
In the U.S., we’ve recently seen remarkable progress in developing therapeutics for diseases like Alzheimer’s, where no approved disease-slowing treatments previously existed. While breakthroughs such as Biogen and Eisai’s Leqembi and Eli Lilly’s Kisunla have led to modest improvements in slowing cognitive decline in Alzheimer’s patients, there remains a need for safer, more effective and more targeted medications that treat the underlying causes of disease.
I am acutely aware of the growing need for more effective diagnostics and therapies to alleviate the suffering of people with neurological disorders, having witnessed firsthand the devastating toll that dementia took on my mother, who experienced 15 years of declining health without truly effective diagnostic or treatment options. At Sunbird Bio, where I serve as executive chairman and CEO, I lead a team of experts developing a broad panel of blood-based diagnostic tests that we believe could help transform care for patients suffering from neurological diseases.
Of course, I’m not alone in being personally affected by these conditions. Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and other neurological disorders affect more than 100 million people globally and have vexed scientists and physicians for generations. Even with the most modern scientific methods, the intricate nature of the brain and profound complexity of these disorders have kept diagnostic and treatment solutions out of reach.
Very fortunately, discoveries and innovations have accelerated over the past two to three years, and we are finally turning a corner as we gain unprecedented insights into the underlying biology of neurological diseases. Scientific research is unveiling their varying causes and indicators, and these discoveries are fueling dramatic advances in treatment—as well as an unprecedented need for accessible, affordable and complete diagnostics.
Breakthroughs Reshaping Neurology
We’ve known for some time that most neurological diseases are associated with certain proteins that aggregate in the brain. More recently, we’ve learned that at least 50 percent of patients have multiple and different types of protein aggregates in the brain—some of which were previously believed to be solely associated with a different neurological disorder. For example, patients with Alzheimer’s may have not only amyloid plaques but also aggregated alpha-synuclein, a protein associated with Parkinson’s disease or Lewy body dementia pathology. This means that their situation is compounded by co-pathologies. Unfortunately, we don’t yet have a comprehensive diagnostic platform that can easily detect many of these proteins.
In Alzheimer’s disease, we now have two disease-modifying therapeutics on the market, Leqembi and Kisunla, and more than 100 additional compounds in development that target various proteins associated with the disease. Despite the benefits that new treatments have shown in slowing disease progression in patients with aggregated beta amyloid, the lack of diagnostics has made it difficult to conduct studies that would show the safety and efficacy of the therapeutics in patients with co-pathologies. This information could completely transform the way patients are treated.
As we gain a deeper understanding of the range of protein aggregates involved in disease pathology and co-pathologies and get a fuller picture of the brain’s health, the need for diagnostics that can enable the development of more effective, precise therapies becomes increasingly compelling. We have seen how precision diagnoses and treatment have meaningfully altered survival rates in many types of cancer. For example, medical professionals no longer treat “breast cancer,” but instead treat HER2-negative breast cancer or triple-negative breast cancer or one of many other biomarker-specific forms of the disease. Our understanding of these biomarkers has led to the approval of treatments that otherwise may have failed—as a result, patients are experiencing meaningfully better outcomes.
In neurology, we may finally be on the cusp of joining oncology in the era of precision medicine. To make this a reality and accelerate development of effective therapies for neurological diseases, we still need to overcome several key challenges. Chief among them is the availability of diagnostic tests that can detect the full range of disease-relevant biomarkers quickly, accurately and at scale. As in oncology, this could ultimately lead to breakthroughs in therapies for certain patient segments and the introduction of combinatorial therapeutics that improve patient outcomes.
Complex Challenges
Neurodegenerative disorders are notoriously difficult to diagnose, and until very recently, diagnostic options were limited to methods that are inaccessible, expensive and not scalable, such as PET scans or cerebrospinal fluid testing. Most of the individuals impacted by these disorders are diagnosed through subjective cognitive tests. As a result, as many as 90 percent of patients with mild cognitive impairment, one of the earliest symptoms of Alzheimer’s and Parkinson’s, remain undiagnosed. Further, we don’t have any diagnostic tests available that can detect various protein aggregates directly from the brain, which is critical to accurately diagnose disease and co-pathologies.
Not only has the lack of effective diagnostics prevented timely and accurate patient diagnoses, it has also severely hampered the speed and success of therapeutic development, including clinical trial design and targeting, patient stratification for trials, monitoring of therapeutic efficacy and appropriate treatment adjustment. In particular, the lack of ability to detect co-pathologies in patients with neurological disorders may have contributed to the currently inadequate therapeutic landscape. To put it another way, some therapies that have failed in clinical trials may have succeeded for specific segments of the patient population, but without knowing relevant co-pathologies, the appropriate patients were not identified and evaluated.
Recent discoveries clarifying the roles that different protein aggregates play in neurological disease pathology highlight the need for better diagnostic approaches and technologies. To truly realize the precision medicine era for neurology, we need a comprehensive, flexible and scalable blood-based panel of diagnostic tests that can detect all of the proteins that may contribute to the pathology of neurological disorders.
This critical tool would give us a holistic, precise view of a patient’s neurological health to drive earlier, more accurate diagnoses, identify co-pathologies and facilitate therapeutic monitoring. This approach would also accelerate the discovery, development and availability of effective new precision therapies that target specific disease biomarkers, significantly reducing the time and money invested into clinical trials and drug development. We need this now in order to enable a future in which far fewer people experience the devastating decline of neurological health.
