How Strategic De-Risking is Fueling Parkinson’s Treatment Development

Developing new medicines and devices for Parkinson's disease (PD) is a high-stakes endeavor that can be costly, complex and often uncertain. But a growing number of promising therapeutic programs suggest that de-risking this process may be the key to moving promising therapies forward. By pairing targeted funding with scientific and collaborative support, The Michael J. Fox Foundation (MJFF) helps companies overcome early development barriers, strengthening the therapeutics pipeline and accelerating clinical trials.

"De-risking isn't just about funding early science - it's about giving promising ideas the support they need to mature and demonstrate their value," said Shalini Padmanabhan, PhD, head of translational research at MJFF. "When we reduce early uncertainty, we help move potential treatments forward faster and more efficiently."

De-risking is one way MJFF works to improve the treatment pipeline and speed the pace of clinical trials. Success in this area means generating the data, partnerships, investments, and momentum needed to advance promising therapies into well-designed clinical trials and, ultimately, closer to people living with Parkinson's. Increasingly, that strategy is paying off.

Engaging Genetic Targets

Developing new therapies requires understanding underlying PD biology. Genetics and other biological studies have identified a number of cellular proteins and pathways that may contribute to how PD develops and progresses. One of the most advanced areas of this work focuses on the LRRK2 gene, one of the most common genetic causes of Parkinson's. As knowledge in the genetics of PD grows, researchers are turning these insights into new treatments designed to directly target genes such as LRRK2.

"LRRK2 research shows what's possible when genetic discovery is paired with sustained, strategic investment," said Dr. Padmanabhan. "We now have tangible opportunities to translate decades of genetic insight into therapies that could meaningfully change the course of Parkinson's."

In some people with PD, mutations in the LRRK2 gene cause its enzyme activity to become abnormally high, disrupting normal cellular cleanup and contributing to toxic protein buildup in the brain. MJFF recently awarded SciNeuro Pharmaceuticals $5 million to support the development of SNP614, a synthetic gene snippet designed to act on the LRRK2 gene and reduce LRRK2 protein levels. Funding from MJFF, along with $53 million in equity financing raised by SciNeuro from new and existing investors, will help move the therapy closer to human clinical trials.

To further advance their work into LRRK2 therapeutics, SciNeuro has joined MJFF's LRRK2 Investigative Therapeutics Exchange (LITE). LITE is a collaborative program that brings together researchers, clinicians and industry experts to accelerate LRRK2-focused therapies and biomarker development by sharing data, tools and discoveries in real time.

Advancing Mitochondrial Health

While targeting LRRK2 addresses an important genetic driver of Parkinson's disease, genetic and biological studies have also shown PD is driven by biological pathways involved in cellular dysfunction, including impaired protein clearance, chronic inflammation, and disrupted energy regulation. Many of these processes involve mitochondria, energy-producing structures within cells that are essential for neuronal health, making therapies that improve mitochondrial health a promising pathway for slowing disease progression.

"Dopamine-producing neurons are incredibly energy-hungry," said Dr. Padmanabhan. "When their mitochondria stop functioning properly, those cells are especially vulnerable to damage and death. Protecting mitochondrial health is critical to protecting these neurons."

Building on this understanding of mitochondrial health, MJFF, in partnership with Parkinson's UK, has awarded Mission Therapeutics $5.2 million to support the clinical development of MTX325, a drug designed to improve mitochondrial quality control in neurons. The drug inhibits USP30, a protein that interferes with the removal of damaged mitochondria. MJFF's support along with $13.3 million raised by Mission Therapeutics, will help test MTX325 in people with PD for the first time, seeing if the drug impacts mitochondrial quality control and other PD-related biomarkers.

Another company targeting USP30 is Vincere Biosciences. MJFF has long supported Vincere's efforts to develop their drug, VB-08. In 2022 and 2024, MJFF supported preclinical studies that evaluated the safety and dosing level of VB-08 and confirmed the drug impacted mitochondria removal. Most recently, in 2025, MJFF awarded additional funding to Vincere Biosciences Inc. to gather preclinical data on the safety and impact of VB-08 at higher doses. Preclinical data on the safety, dosing level and therapeutic impact of VB-08 are especially important, as this information is necessary before the therapy can be considered for human trials.

A company taking a different approach to mitochondrial cleanup is NRG Therapeutics. In the fall of 2024, MJFF awarded the company a $5 million grant to help support the development of NRG5051, a drug that targets openings in the cell wall of mitochondria called mitochondrial permeability transition pores (mPTP). These channels open when mitochondria are stressed, allowing an influx of small molecules that causes the mitochondria to swell and burst, leading to neuronal death.

MJFF's funding supported preclinical studies that gathered information on the quality, consistency and safety of NRG5051 - information needed before human clinical trials can begin. Building on this foundation, NRG Therapeutics recently announced they have gathered $67 million in investments to conduct a Phase 1b study of NRG5051. This study will test the therapeutic potential of the drug for treating amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) and collect clinical data in people with PD.

Rethinking Deep Brain Stimulation

In addition to advancing therapies that target the underlying biology of Parkinson's disease, researchers are also focused on improving treatments for symptoms that most directly affect daily life. Persistent motor symptoms, such as freezing of gait, remain a major unmet need, even as disease-modifying research advances.

"When freezing of gait occurs, people can suddenly feel stuck and unable to move forward, increasing their risk for falls," said Dr. Padmanabhan. "Improving therapies in this area could make a meaningful difference in how people navigate their daily lives."

To help address the need for therapeutics in this area, MJFF supported Newronika in developing an adaptive deep brain stimulation (DBS) system. In DBS, a surgically implanted device sends electrical signals to the brain. These signals regulate communication between neurons, helping the brain control movement. Most currently used DBS systems provide a static and unchanging level of stimulation, but Newronika's system is different. It uses real-time information from the brain to adapt and change the level of electrical stimulation, making it personalized to each person and, hopefully, more effective.

In early 2025, Newronika received FDA approval to begin human testing under an investigational device exemption. These trials will compare adaptive DBS to standard systems in people with advanced Parkinson's. The outcome of this trial will provide critical evidence needed to gain FDA approval for their adaptive device so it can become available to the public.

Investing in What Comes Next

These projects represent just a snapshot of how MJFF is accelerating therapeutic development and clinical trials by reducing early uncertainty in the therapeutic-development process and supporting rigorous science. By de-risking therapeutic development, MJFF helps ensure that promising ideas are advanced and tested rather than abandoned.

"Our goal is to make sure good ideas don't stall because of early risk," said Dr. Padmanabhan. "By stepping in early, we help ensure that the most promising therapies are tested, refined, and ultimately delivered to the people who need them."

As these programs and others advance, MJFF remains focused on pushing the boundaries of discovery to build the preventative therapies and treatments of tomorrow.

• Claire Cole, PhD

  Director of Research Communications