Moving From Symptom Management to Disease Modification in Parkinson’s Research: Q&A with Dr. Jan Stoehr

In 2023, Pharmaceutical Executive reported on AbbVie’s acquisition of Mitokinin, a biotech developing treatment’s for Parkinson’s disease. At the time, representatives for AbbVie stated that the acquisition was a direct effort to improve its Parkinson treatment pipeline, specifically in ways that prevent the progression of the disease.

Since then, that mindset has continued to grow at AbbVie.

Dr. Jan Stoehr, a neuroscience researcher at AbbVie, spoke with Pharmaceutical Executive about how the field is shifting from managing symptoms after they appear to targeting the underlying protein misfolding and aggregation that drives Parkinson's disease progression—and why intervening earlier, before the disease spreads across the brain, is the central challenge defining the next generation of neuroscience therapeutics.

Pharmaceutical Executive: How is the field shifting from symptom management to disease modification?
Dr. Jan Stoehr: The biggest shift in neurodegenerative disease research is the move upstream, targeting underlying disease biology to prevent disease progression. For many years, treatment for these diseases has focused primarily on managing symptoms after they appear. These therapies can make a meaningful difference for patients, but they do not necessarily address the biological processes driving disease and could become less effective over time as the disease advances. By addressing both the symptoms and underlying disease biology, we have an opportunity to potentially slow disease progression and extend the reach of symptomatic therapeutics to help support patients.

In Parkinson’s disease, the challenge is that the condition does not stand still. Scientists currently understand that the disease is caused by a certain protein misfolding, aggregating, and disrupting function and communication between neurons in the brain. Once that process starts, the disease can spread across the brain, almost like a domino effect.

Disease modification aims to intervene in exactly this process. In terms of therapeutic development––rather than focusing solely on symptom control, the goal is to potentially slow, delay, or otherwise alter the course of neurological disease progression.

At AbbVie, our approach to the next generation of neuroscience research is guided by the exploration of symptomatic control combined with disease modification.

PE: How do biomarkers help identify the disease earlier?
Stoehr: We now understand that to potentially slow disease progression, we must target the underlying disease biology, and sooner, before it has a chance to progress to further parts of the brain. Biomarkers provide a window into this disease biology that we simply did not have before. That is critical because many neurodegenerative diseases can begin years, sometimes decades, before a person receives a diagnosis or experiences noticeable symptoms. By the time they appear, significant changes may already have occurred in the brain. Biomarkers can help us identify biological changes earlier, understand how much or how far a patient’s disease has progressed and help determine if a patient may be appropriate or eligible for specific clinical trials.

Researchers are exploring a wide range of biomarkers, including measures from blood, cerebrospinal fluid, imaging and digital assessments. Together, these tools can support early detection, improve patient stratification, measure disease progression, and understand if a therapy is engaging its intended target.

Potential treatment options may not depend on one biomarker alone; instead, they may rely on integrating multiple sources of biological and clinical data to build a more complete picture of disease. At AbbVie, my team and I are focused on researching the foundational mechanisms of Parkinson’s disease biology, and we’ve been incorporating these technologies into our research to help inform drug discovery and development to become more precise, data-driven, and patient-centered.

PE: What role does patient experience play in neuroscience research?
Stoehr: Patient experience is what grounds our scientific research.

As scientists, we can look under a microscope and see how neurons degenerate, but that does not tell us what it feels like to live day-to-day with a neurodegenerative disease. If you have seen one patient with a brain disorder, you have only seen one patient. These conditions can present very differently from person to person. The unique experiences of each patient and caregiver help us understand that diversity in ways data alone cannot.

In Parkinson’s disease, many people think first of motor symptoms such as tremor or changes in movement. Those symptoms matter deeply, but they are not the full story. Patients may also experience cognitive changes, depression, hallucinations, or other non-motor symptoms that can have a significant impact on their quality of life and on their families.

When we listen to patients and caregivers, we gain a better understanding of what meaningful progress really looks like, from maintaining independence to reducing caregiver burden. Those insights help shape the questions we ask in research and how we measure outcomes. Ultimately, they help ensure that scientific advances are focused not only on disease biology, but also on what matters most to patients.

PE: What are the biggest challenges facing neurodegenerative disease research?
Stoehr: One of the biggest challenges is that neurodegenerative diseases are biologically complex and clinically heterogeneous. Conditions like Parkinson’s and Alzheimer’s disease are not driven by a single pathway or mechanism, and they do not look the same in every patient. That makes it difficult to identify the right therapeutic targets and determine which approaches may be most relevant for specific patient populations.

As we’ve discussed, timing is another major challenge. By the time a patient typically receives a diagnosis, the disease has already spread. That is why there is such a strong focus on biomarkers and other tools that may help us detect disease earlier, when intervention may have a greater opportunity to affect progression, and therefore patient outcomes.

Measuring success is also challenging. In many neurodegenerative diseases, progression can be slow and variable, making it difficult to demonstrate whether a therapy is not only improving symptoms in the near term, but truly changing the trajectory of disease. Studies often need to be large, carefully designed, and conducted over extended periods to answer those questions.