A new era in Alzheimer's R&D: Dual approach to disease modification and symptom management

‘Disease modification’ has long been the ultimate goal in neurodegenerative diseases, including Alzheimer’s disease. Despite decades of research, funding and collective initiatives, it was only very recently that the community has started to see forward progress. As researchers work to advance disease-modifying breakthroughs, we must also help patients and their families better manage the day-to-day challenges of the disease. It’s not enough to focus on just half of the Alzheimer’s disease experience.

Researchers at Bristol Myers Squibb are taking a holistic approach to Alzheimer’s disease, dually pursuing investigational therapeutics that aim to meaningfully slow disease progression, ease patient symptoms and help to give families and caregivers back some of what the disease has taken away. Managing the neuropsychiatric symptoms of Alzheimer’s disease, such as hallucinations and delusions, agitation and effects of cognitive decline, will undoubtedly improve the quality of life for patients and the people who care for them. Yet we still have little to offer patients and their families who are suffering from these symptoms.

The challenge we are confronting

Affecting an estimated 6.9 million Americans, Alzheimer’s disease is a progressive, multifaceted and devastating neurodegenerative illness and the most common cause of dementia—accounting for up to 80% of cases. Accumulating damage to the neurons in the brain has drastic consequences for cognition, resulting in memory loss, difficulty speaking or writing and problems completing familiar daily tasks, all of which challenge the ability to function and relate to others on a day-to-day basis. As a result, the burden of care in the face of an unforgiving disease often falls to families and loved ones.

The quest for disease-modifying therapies is an important one, not least because changing the progression of the disease changes the course of someone’s life. But the symptoms of Alzheimer’s disease are often front and center as the most challenging component of the disease. As Alzheimer’s disease progresses, it can affect mood and personality. Patients can eventually develop neuropsychiatric symptoms that are prevalent across all forms of dementia. This can manifest as visual and auditory hallucinations, paranoia, anxiety and sometimes extreme agitation, putting increased strain on caregiver relationships during an already difficult time.

Symptomatic-focused therapies have the potential to make near-term differences for patients and their families. So, while the research and development of treatments that slow or stop the progression of the underlying disease remains a major goal, treatments that manage Alzheimer’s disease symptoms are of equal priority.

Working to provide a continuum of care

We know that to take on both sides of this devastating disease, our research teams will need to take distinct scientific approaches. Through these different lenses, we are investigating ways to provide a continuum of care in Alzheimer’s disease, one that spans from slowing progression to helping patients and families better manage symptoms.

• Disease modification: Amyloid and tau are two widely recognized biomarkers used in the diagnosis and monitoring of Alzheimer’s disease. The progression of tau pathology is closely correlated with clinical progression. Tau deposition correlates with symptom onset at a younger age and faster disease progression, and with neurodegeneration which contributes to cognitive impairment.  Bristol Myers Squibb is investigating ways to more precisely target and remove pathogenic tau from the brain, in particular tau proteins that are found outside of neurons, which are thought to be a major cause of disease progression. This approach is currently being studied in a Phase 2 clinical trial.
  
  
• Symptom management: Multiple targets whose modulation has the potential to positively affect neuropsychiatric symptoms of Alzheimer’s disease, including hallucinations and delusions, agitation and cognitive decline are being explored to bring forward new symptomatic therapies for patients. For example, muscarinic receptors in the brain are a promising potential target in Alzheimer’s disease. Bristol Myers Squibb is exploring novel ways to treat the symptoms of psychosis in Alzheimer’s disease by selectively stimulating muscarinic receptors, an approach currently under investigation in late-stage clinical trials. Other novel approaches to symptom management are also being investigated.

Breakthroughs that modify Alzheimer’s disease remain mission critical, but our researchers at Bristol Myers Squibb are also centering on the human experience. By balancing cutting-edge research into tau pathology with a focus on addressing the day-to-day needs of patients and caregivers, we’re pushing the boundaries of scientific innovation to develop meaningful new therapeutics across the continuum of Alzheimer’s disease care and for the benefit of the full community impacted.