Bristol Myers Squibb is advancing neuroscience R&D through breakthroughs in human biology, biomarkers and computational science—pioneering new approaches to slow disease progression and improve outcomes for patients living with serious neurological conditions.
Neurological conditions are inherently complex and represent some of the most challenging diseases.
One particular challenge is the inability to easily biopsy tissue from the brain.
Advancements in biomarkers and medical imaging have been instrumental to groundbreaking research, clinical trials and treatment breakthroughs for neurological diseases.
Neuroimaging is often used in combination with fluid biomarkers from samples such as plasma and cerebrospinal fluid.
Together, they provide a window into the brain, helping answer key questions regarding disease biology and providing insight into if and how investigational medicines are working.
In the research and development of new medicines, neuroimaging can help determine important therapeutic properties, such as the ability of the medicine to get to the right place in the brain, whether the medicine is engaging the intended target, how much of the target is being engaged and how the medicine is affecting the target.
Two imaging technologies are especially notable in neuroscience research and development.
Magnetic resonance imaging, or MRI, is primarily used to reveal the structure of the brain and positron emission tomography, or PET, is used to visualize molecular properties and processes.
MRI creates detailed images of the brain by leveraging the fact that different tissues contain varying amounts of water. By using a strong magnetic field and radiofrequency waves to manipulate the water molecules, MRI produces detailed images of different tissue types.
Researchers can use these images to understand changes in the brain that may occur due to neurological conditions or as a response to a medicine.
PET can directly track therapeutics as they move through and affect the brain, which allows for a detailed understanding of how the medicine might affect the body and disease.
This is done at BMS by creating tracer molecules and modified versions of medicines that have a radioactive atom attached. The radioactive atom is created with a cyclotron or particle accelerator and attached to a tracer molecule or the medicine being studied.
The resulting molecules, called radioligands, can then be followed throughout the brain via PET scanners, as small particles called positrons are emitted.
The ability to create radioligands with an in-house cyclotron is a unique capability and enables BMS to accelerate the discovery and development of new medicines.
Neuroimaging has a wide-ranging impact on both neuroscience research and clinical trials, which results in significant time and cost savings.
As the field enters a new era in neuroscience, Bristol Myers Squibb continues to pursue bold science to deliver meaningful therapies for patients.
We are motivated by the rapid evolution of scientific knowledge within neuroscience, which we are using to discover, develop, and deliver transformative medicines for some of the most challenging diseases of our time.
The brain presents a unique challenge for researchers. Unlike any other organ in the body, the brain is both highly complex and largely inaccessible, consisting of complicated networks of neurons and neurotransmitters. Gaining insight into its intricate inner workings—without an invasive procedure— requires specialized tools and innovative approaches. Neuroimaging technologies, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), allow researchers to visualize activity and changes within the brain. These tools offer new understanding of disease processes and real-time feedback indicating if an investigational medicine is achieving its intended biological effect. In the interview below, BMS scientists describe how cutting-edge advancements in neuroimaging are accelerating progress in neuroscience R&D and providing new insights into the brain’s complexities.
What is neuroimaging and how does it help solve some of the challenges in neuroscience R&D?
Shuyan Du, PhD, executive director, Imaging, PMBATS, TMCP
Answer: Neuroimaging refers to a range of imaging technologies in radiology and nuclear medicine which have revolutionized neuroscience by providing a non-invasive way to visualize the anatomy and function of the central nervous system (CNS) in both healthy individuals and those living with neurological conditions. Neuroimaging plays a crucial role for diagnosing neurological conditions, monitoring disease progression and assessing treatment efficacy and/or safety.
One notable example is the application of neuroimaging in Alzheimer's disease:
- MRI provides detailed images of the brain structure to characterize early signs of Alzheimer’s disease, such as the loss of brain cells or shrinking of the brain. In addition to monitoring disease progression, MRI can also be used to assess the safety of treatments.
- PET scans, including amyloid PET and tau PET, can visualize amyloid plaques and tau tangles, which are hallmark features of Alzheimer’s disease. Amyloid PET and tau PET are critical for diagnosing the condition, monitoring the accumulation of these disease-causing proteins and evaluating the effectiveness of treatments aimed at reducing amyloid and tau levels.
How do you see neuroimaging continuing to transform neuroscience?
Shuyan: Neuroimaging is poised to continue transforming neuroscience through the advancement in imaging technologies and integration with data science, including artificial intelligence (AI) and machine learning (ML). What’s more, we are working across teams to find new ways to collaborate and leverage these capabilities to confidently identify disease pathology early on and accelerate the discovery and development of novel medicines faster than ever before. One example of this continued transformation is in clinical trials studying novel treatments for Alzheimer’s disease, where neuroimaging provides powerful ways to improve patient selection and to objectively and non-invasively monitor treatments for safety and efficacy.
How does Bristol Myers Squibb apply neuroimaging within R&D?
Joel Schwartz, PhD, scientific director, Translational discovery, Neuroscience Research
Answer: Teams at Bristol Myers Squibb use neuroimaging to inform patient selection and better understand target engagement (making sure the medicine is doing what it is intended to do) and pharmacodynamics, or how the drug interacts with and affects the body and brain, for our investigational medicines. Neuroscience is unique to other therapeutic areas—we cannot easily measure the direct effects of a medicine in the CNS because the brain is protected behind the skull and the blood-brain barrier. We can access the fluid around the brain, but this may not reflect the changes occurring inside the neurons, which are the cells that primarily make up the brain and CNS. Neuroimaging allows us to continuously measure target engagement and pharmacodynamics within the brain, providing scientists with essential information on whether the medicine is working.
How is the team using predictive science in combination with neuroimaging to accelerate drug discovery and development?
Adam Smith, PhD, scientific senior director, Clinical neuroscience imaging, PMBATS, TMCP
Answer: The combination of predictive science and neuroimaging is transforming how teams approach drug discovery and development, especially for complex neurological conditions like Alzheimer’s disease, multiple sclerosis, depression and schizophrenia. This integration happens across the R&D continuum to accelerate and streamline how we advance investigational medicines in many ways:
- Understanding disease: Neuroimaging approaches can reveal brain regions, pathways and targets that are disrupted in a disease. Predictive models—often powered by AI and ML—then analyze this imaging data alongside genetic, molecular and clinical information to identify promising drug targets, proteins or pathways that may contribute to disease.
- Studying potential new medicines: Investigational medicines can also be examined using predictive technologies in combination with neuroimaging tools to see if they can affect targets and pathways with the aim of restoring normal brain function or halting and/or reversing disease processes and symptoms.
- Improving clinical trials: In the clinic, imaging biomarkers may be used to predict disease progression or treatment response as well as validate the utility and reliability of other kinds of biomarkers. Predictive science helps to further validate these biomarkers by finding links with clinical outcomes across large datasets, ultimately getting more medicines to patients faster. Neuroimaging combined with AI and ML can also help identify distinct patient groups for inclusion in clinical trials as well as potentially accelerate the duration of trials by predicting long term outcomes based on early patient responses to treatment.
In short, neuroimaging has a wide-ranging impact on both neuroscience research and clinical trials - increasing the likelihood of scientific and therapeutic breakthroughs, while also delivering significant time and cost savings. As neuroimaging technologies continue to evolve, we will undoubtedly uncover more about the brain’s intricate architecture. These insights will pave the way for transformative progress in our understanding of neuropsychiatric and neurological conditions, leading to meaningful advances in patient care.