Parkinson’s Disease Therapeutic Conference Focuses on Critical Tools and Disease-modifying Drugs

Since its founding in 2000, The Michael J. Fox Foundation (MJFF) has pursued a singular mission to accelerate the next generation of therapies for people with Parkinson's disease (PD). To achieve that goal, the Foundation funds therapies, supports cutting-edge science, develops research tools, harnesses the potential of emerging technology and mobilizes stakeholders. This year’s annual Parkinson’s Disease Therapeutic Conference (PDTC), held October 16 in New York City, highlighted the benefits of this ambitious approach — and the potential it holds for improving the future of PD. 

In its 17th year, PDTC, the only scientific conference worldwide that is focused exclusively on Parkinson's disease drug development, hosted an overflow audience of more than 300 researchers and industry leaders for an agenda that revealed a shift underway in therapeutic development for the disease.  

While 25 years ago, the therapeutic landscape for PD focused almost exclusively on managing symptoms by replacing dopamine, “we are facing a very different therapeutic landscape” today, according to Sohini Chowdhury, chief program officer at MJFF, in opening remarks to the conference attendees. 

She cited growing knowledge of the disease and an expanding array of research-enabling tools that are resulting in a surge of activity in the development of urgently needed therapeutics to slow or stop the disease from progressing. Promising advances in the development of these so-called “disease-modifying therapies” — and essential tools to measure their impact on the disease process — forecast a field on the verge of a new way of treating PD.  

The event featured cutting-edge discussions on new approaches to treating Parkinson’s and on critical tools for detecting and measuring changes in the disease and accelerating clinical trials. Here’s an overview of the takeaways. 

Biomarkers Are Essential Tools for Achieving Next-Generation Therapies 

Much of the improving therapeutic landscape for PD rests on biomarker tools, which are a major focus area for MJFF. MJFF supports a wide array of research through its biomarker advancement programs and imaging work.  

The MJFF-led 2023 breakthrough discovery of a biomarker tool that detects the PD’s misfolded alpha-synuclein protein has helped dramatically accelerate the search for next-generation treatments. This was quickly followed by ongoing work to evolve the tool — so that it is more informative about Parkinson’s progression over time and more readily integrated into drug trials — and apply it to learn about the presence of alpha-synuclein pathology across a range of neurodegenerative diseases. At the same time, researchers also are pursuing additional biomarkers, including sophisticated imaging tracers that would allow researchers, for the first time ever, to visualize Parkinson’s-related biology in the living brain. 

This year’s PDTC featured groundbreaking updates on next-generation biomarkers to track biological changes in the disease and reveal how treatments impact its progression.  

• Presenters from the Institute for Neurodegenerative Disorders, Xing Imaging and Shanghai Institute of Organic Chemistry shared major advances in imaging PD, including a new analytic method that makes DaTscan (an imaging test to detect PD) more sensitive for measuring change over time in dopamine (the chemical lost in PD) and a PET scan innovation that can do something the field been striving to achieve: measure changes in the amount of alpha-synuclein in the brain. 
• The audience learned about a microfluidics-based technology for measuring changes in the amount of alpha-synuclein in spinal fluid. The lab at Cambridge University that developed the technology now is scaling it for use in clinical trials. 

These advances can make clinical trials faster by reducing the number of participants needed, and clearer by revealing whether a therapy being tested affects the biology that underlies the disease. At the same time their use can expand understanding of how the disease starts and progresses, information that can help inform treatment approaches.  

In addition to their scientific value, biomarkers also are key to the business of drug development. As one speaker noted, they are essential to better PD treatments because they help build evidence that convinces investors to advance more drugs further in clinical trials. 

Diverse Range of Disease-modifying Therapies Fill the Clinical Pipeline 

PDTC also highlighted two biological pathways of growing therapeutic interest for PD.  

One session focused on therapies targeting the endolysosome system that handles the breakdown and recycling of materials in cells. This system is a growing area of interest for PD therapeutic development, according to the session moderator, due to compelling evidence indicating that autophagic clearance — the process by which cells break down and remove misfolded alpha-synuclein and other damaged proteins — is associated with the risk for disease. Data also indicates that people with Parkinson's disease carry an increased burden of variants in genes associated with lysosomal storage disorders. The session featured scientific updates on notable endolysosomal-targeted therapeutics:  

• Mutations in LRRK2, among the most common causes of inherited Parkinson’s, trigger cellular dysfunctions that impair the endolysosomal system and disrupt the clearance of alpha-synuclein. The audience heard about progress on a LRRK2-targeted drug from Montara Therapeutics that is specially designed to penetrate the blood–brain barrier that blocks many drugs from entering the brain. Montara is a member of MJFF’s ambitious LRRK2 Investigative Therapeutics Exchange (LITE) program, which is designed to both fast-track the development of LRRK2-targeted drugs for PD and advance progress toward new LRRK2-relevant clinical biomarkers.
• Other companies reported on different approaches to restore functioning to the endolysosomal system. Endlyz Therapeutics reported on its efforts to target ATP13A2 and ATP10B to restore lysosomal function, based on evidence that changes in these genes can cause a buildup of cellular waste that leads to PD. Vanqua Bio provided an update on its drug targeting the inherited mutations in the GBA gene that impair the breakdown of cellular waste. Lysoway Therapeutics provided information on its drug to activate TRPML1, an endolysosomal ion channel whose dysfunction is linked to PD. TRPML1 is one of five priority targets of MJFF's recently launched Targets to Therapies Initiative that is expanding and mechanistically validating promising but understudied targets, with the goal of building evidence that reduces the risk of biotech and pharmaceutical investment in exploring new treatment opportunities in the PD field.  

Another session focused on therapies to protect the brain from inflammation, which contributes to Parkinson’s by causing damage to dopamine-producing neurons, although it remains unclear if inflammation is a trigger or a consequence of the disease. The session featured reports from three companies — Longevity Biotech, Ventyx Biosciences and Vesper Biosciences — taking different approaches to target immune dysfunction that is linked to inflammation. As with therapies targeting the endolysosomal system, there is hope that therapies to fix dysfunction in the immune system will have an effect on slowing the progression of PD.  

Building on Lessons Learned to Find the Cure for Parkinson’s 

Bringing researchers, clinicians and thought leaders together for events like PDTC creates space to share new ideas and tackle barriers to better treatments. 

In a keynote address, Samantha Budd Haeberlein, PhD, a leader in international drug development for neurological disorders, acknowledged the daunting challenges that make neurodegenerative diseases like PD hard to treat. She cited the variable biological factors that contribute to PD, difficulties posed by a disease process that may start long before diagnosis, and the blood–brain barrier that blocks many drugs from reaching the brain where they are needed.  

But sounding much like MJFF’s founder Michael J. Fox, who so often tackles challenges through a lens of optimism, she noted “difficult doesn’t mean that we don’t do it.” She cited successes in the Alzheimer’s disease field, which since 2021 include three approved disease-modifying therapies that slow the progression of disease by addressing the underlying pathophysiology.  

Moreover, she expressed hope that disease-modifying therapies for Parkinson’s are closer than ever because of ongoing fieldwide efforts to learn from the past and to collaborate, communicate and share progress so that promising ideas can continue to accelerate in clinical testing and advance faster toward regulatory approval and into patients’ hands.