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.
[00:00-00:11] R. Hargreaves
Scientists are inherently curious and they're persistent and breakthroughs don't really always happen easily, but they're resilient.
[00:12-00:16] R. Hargreaves
Understanding the brain is probably one of the most complex pieces of biology.
[00:17-00:33] R. Hargreaves
Not only is the access to it restricted, but also it's actually made up of millions and millions of cells that are interconnected, forming associated circuits that drive all of the emotions, motor behavior, senses.
[00:34-00:40] R. Hargreaves
And understanding these in health then allows us to examine them in disease.
[00:45-00:50] K. Rhodes
Neurodegenerative and neuropsychiatric diseases represent some of the greatest therapeutic challenges of our time.
[00:51-01:01] K. Rhodes
My grandfather actually drove my interest in science and medicine. As he aged, he developed the symptoms of Parkinson's disease, and so I watched his experience with neurodegenerative disease.
[01:02-01:08] K. Rhodes
I saw the impact that that had on him as an individual and as a clinician on the family.
[01:09-01:20] K. Rhodes
These diseases have a huge impact on families, on their caregivers, obviously on the patient themselves and also on society. And as the disease progresses, those impacts become greater.
[01:22-01:27] S. John
Even with the need for better treatments, progress has been hard fought in neuroscience.
[01:28-01:37] S. John
It's been very iterative, we have tested many hypotheses in the clinic and many of those have failed. But with each hypothesis we test, we learn something.
[01:38-01:46] S. John
And we learn something about the human causal biology or the root cause of disease, or we learn something about the targets and the medicines that we've tested.
[01:47-01:54] S. John
Until quite recently, the tools and the knowledge to help us make progress just didn't exist.
[01:58-02:07] K. Rhodes
We're at an incredible new frontier in neuroscience, where we have this deep understanding of the causal drivers of neurodegenerative and psychiatric diseases.
[02:08-02:16] K. Rhodes
Insights from the genetics and the underlying pathology of disease give us clear insights into potential treatment paths that we can take.
[02:17-02:49] S. John
The way that industry and academia have come together to develop neuroimaging techniques and also less invasive biomarker measures that allow us to measure neuroscience, biomarkers from the blood have been hugely powerful. We have now blood-based biomarkers for diseases like Alzheimer's disease and Lou Gehrig's disease and these allow us to really monitor disease and even start to find patients who have pre-symptomatic disease.
[02:50-02:59] S. John
We have much more confidence that we can recruit the right patients with the right pathology at the right time to test the right medicine.
[03:01-03:05] R. Hargreaves
A great example is understanding how Alzheimer's disease progresses over time.
[03:06-03:15] R. Hargreaves
We see the deposition of toxic proteins of amyloid and tau and neuroinflammation within the brain and these occur in a time sequence.
[03:16-03:19] R. Hargreaves
We know where in the disease process we want to intervene.
[03:20-03:34] R. Hargreaves
We now have amyloid therapeutics which are able to slow the progression of the disease and future therapies now have the potential to add on to those and have an even bigger impact.
[03:38-03:56] R. Hargreaves
We have a holistic view of the disease, both from the pathology and from the symptomatology. And our programs really consider that whole human experiences. How can we slow the disease? How are we able to treat the symptoms of the disease? Because that's what's most important to the patient.
[03:57-04:15] K. Rhodes
Whether we're developing an oral drug or an intravenous drug, an antibody or a small molecule, we want to use whatever modality we believe is best to interfere or interact with the underlying biology of disease, guided by that causal human biology.
[04:16-04:21] S. John
Another key to advancing research and development in neuroscience is the use of informatics and predictive sciences at Bristol Myers Squibb.
[04:22-04:42] S. John
Throughout our research history, we generate and collect data and these have become huge data sets. And really, it's the advances in computational methods and mathematics that now allow us to mine those data sets and learn more about targets.
[04:43-04:58] S. John
The goal of these efforts is to enable our research and development teams to run the highest-quality investigational studies faster and more efficiently, and this will enable us to bring transformational medicines to patients more quickly.
[05:03-05:19] K. Rhodes
We have tremendous expertise that we're building across the Bristol Myers Squibb organization that will allow us to efficiently translate discoveries into the laboratory, into our clinical programs, ideally advancing molecules as quickly as possible to treat some devastating diseases.
[05:20-05:35] K. Rhodes
One of the challenges that we still face is delivery of our medicines to the brain. We're actively pursuing technologies that allow us to enhance the transport of molecules across the blood-brain barrier so that they can reach their site of action in the nervous system.
[05:36-05:39] K. Rhodes
I believe there's a tremendous progress on the horizon in neuroscience.
[05:40-05:53] R. Hargreaves
It's a really fulfilling time when you can see that you can bring benefit to people through your career and through work and science that you love to do, so I think it's actually a privilege to work on these problems.
[05:54-06:09] S. John
I really became a geneticist because I just love the idea that genetics can help us answer some of the really tough questions. As I pursued my career, it became obvious that neuroscience is almost the sort of last frontier of biology.
[06:10-06:25] S. John
My dad was diagnosed with schizophrenia when I was a girl, and as I grew up I really saw and understood how invasive and debilitating these diseases can be on all aspects of a person's life.
[06:26-06:37] S. John
What's been really amazing to see is the way that people do come together and share our learnings so that we can accomplish things in neuroscience that simply wouldn't have been possible before.
What you should know: |
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Neurodegenerative and neuropsychiatric conditions are inherently complex and represent some of the greatest challenges of our time. Our experts at Bristol Myers Squibb are boldly pursuing novel approaches with a clear vision to bring new, transformational therapies to patients living with these conditions. Hear from a few of these experts below as they unpack the progress ushering in a new golden era of neuroscience research.
New avenues for rapid progress
The neuroscience team at Bristol Myers Squibb is focused on neurological conditions for which there are currently limited options — such as Alzheimer’s disease, autism spectrum disorder, bipolar disorder, multiple sclerosis and schizophrenia — and advancing research of new approaches that may modify the disease or alleviate symptoms. A strong foundation in causal human biology coupled with scientific creativity and serendipitous discovery have led to recent scientific breakthroughs for these conditions and a pipeline with the potential to produce a cascade of new medicines for patients.
“Though some advances in treating neurological and psychiatric disorders have been made over the past 25 years, existing treatments still leave many patients and their families without the relief they urgently need. To address these unmet medical needs, our teams at Bristol Myers Squibb are exploring a broad range of mechanisms and targets with the goal of applying insights related to understanding brain pathways to develop therapies that will have a bigger impact for patients. We already see this approach succeeding in neuropsychiatry with the modulation of muscarinic acetylcholine receptor pathways. We have demonstrated efficacy for this approach in schizophrenia and are looking at how modulating these receptors can potentially treat cognitive and behavioral symptoms across a range of neuropsychiatric conditions. Similarly, with the advancement in understanding the underlying causal biology of Alzheimer’s disease and other neurodegenerative disorders, we are developing and testing novel approaches to treat these devastating conditions.”
Laura Gault, senior vice president, head of development, Neuroscience
Unraveling genetics with artificial intelligence and machine learning
Human genetics has played an immeasurable role in the expansion of our scientific knowledge, revealing key causal human biology and new therapeutic targets. Now, researchers are applying artificial intelligence (AI) and machine learning (ML) to vast data sets to uncover patterns, trends and targets previously unknown.
Sally John, senior vice president, Informatics and Predictive Sciences
“What's been really amazing to see is the way that the industry has come together to share learnings within this new data-rich environment, all so that we can accomplish things in neuroscience that simply wouldn't have been possible before. We have a much deeper understanding of the genetics of neurological disorders than we did even a decade ago; we are gathering insights into the genes that cause disease and contribute to symptom progression and how they influence biomarkers that we can measure. And we are now generating new, highly relevant data from patient-derived cells and cell systems — including neurons, microglia and astrocytes — to further explore the functional impact of disease mutations. For example, we are able to grow a population of motor neurons from people living with ALS that carry disease-causing mutations and look at how they affect the broader genome compared to normal motor neurons. These data can then be analyzed by our skilled scientists using advanced computational methods to find the next generation of new targets and, ultimately, therapies for patients.”
Expanding mechanisms and modalities
Following in the footsteps of diseases such as cancer, neurological disorders have seen rapid progress and expansion in the pathways, targets and modalities that are being explored to slow or stop disease progression and/or alleviate symptoms. Researchers are working diligently to continue identifying new approaches to amplify the potential for breakthroughs across these devastating conditions.
“There have been many recent advances in the exploration and treatment of neurological conditions, particularly Alzheimer’s disease. Over the past decade there has been a shift from focusing solely on the removal of the protein amyloid-beta to a broader range of therapeutic approaches, including targeting the protein tau, improving access of therapeutics to the brain with blood-brain-barrier shuttles and approaches using genetic medicines. The value of tailoring treatments to individual patients based on disease stage and characteristics is now being realized, and we are aligning therapeutic modalities with underlying mechanisms of disease and disease symptoms to enhance patient outcomes and quality of life.”
Richard Hargreaves, senior vice president, Neuroscience, Immunology, Integrative Sciences and Cardiovascular Research
Breaking boundaries with new biomarkers
Biomarkers are transformative tools currently facilitating rapid progress within neuroscience research, particularly in the development of more accurate diagnostic tests and effective treatment strategies as the field strives to bring better care to patients earlier in the course of the disease. In progressive neurodegenerative disorders, such as Alzheimer’s disease, early diagnosis — particularly before symptoms appear — remains an elusive goal. The emergence of blood-based biomarkers could shift this diagnostic paradigm, enabling earlier and more accessible screening for at-risk individuals.
Ken Rhodes, vice president, Neuroscience Research
“To succeed in transforming the treatment of Alzheimer’s disease, we must deeply understand the biological risk factors so we can begin treatment as early as possible with an array of choices at hand, spanning modalities and mechanisms. We need to work towards a future where we evaluate risk for developing Alzheimer’s disease with biomarkers in the same way we use cholesterol to evaluate risk for cardiovascular disease, because Alzheimer’s disease pathology begins many years before symptom onset. We could focus on preventing rather than treating disease. If we can succeed in this regard, we’ll look back and say we have redefined the course of Alzheimer’s disease.”
Bringing CAR T cell therapy to neuroinflammatory disorders
Chimeric antigen receptor (CAR) T cell therapy, which reprograms the body’s own T cells (or fighter cells) to attack diseased cells, has proven to be a transformational modality in certain cancers. But its utility has the potential to extend into other disease areas, including neuroscience. Researchers at Bristol Myers Squibb have deep expertise in cell therapy and are applying that knowledge in the research and development of CAR T cell therapies for neuroinflammatory disorders.
“We are at a pivotal moment in understanding the promise of CAR T cell therapy. We have the opportunity to reset the immune system by directly targeting the underlying cause of neuroinflammatory disorders, such as multiple sclerosis (MS). We hope an immune reset and long-term response are possible for MS based on the therapeutic benefit of B cell depletion and data from the use of stem cell transplant; together, this knowledge provides the scientific basis for the application of CAR T in MS.”
