The Impact of MDF Seed Funding on Scientific Discovery and Investigator Development
The Movement Disorders Foundation's (MDF) Young Investigator Pilot Grant (YIPG) program is designed to provide promising early-career investigators with the resources needed to pursue innovative, high-risk research that can lead to larger studies, additional funding, and ultimately new treatments for people with movement disorders.
The experiences of MDF grantees demonstrate the catalytic impact of this approach. Their projects have:
- generated new scientific knowledge,
- established important research platforms,
- produced preliminary data for larger studies,
- fostered collaborations, and
- helped position the investigators for significant subsequent funding.
Importantly, the grants have also contributed to the development of the investigators themselves. Each has used the initial MDF investment to build expertise, establish or expand an independent research program, develop collaborations, and position their work for continued external support.
Michael Flower, MD, PhD / University College London, UCL Institute of Neurology
Michael Flower, MD, PhD
University College London, UCL Institute of Neurology
Dr. Michael Flower received an MDF Young Investigator Pilot Grant to develop minimally invasive biomarkers capable of measuring Huntington's disease biology—including somatic CAG repeat expansion, DNA repair activity, and treatment response—using extracellular vesicles (EVs) isolated from patient biofluids.
The project represents a technically ambitious approach to one of the major challenges in Huntington's disease research: developing biomarkers that can provide information about molecular changes occurring in the brain without requiring invasive brain tissue sampling.
Advancing the Science
The MDF-supported research has produced several important technical and scientific advances.
The research team successfully optimized methods for isolating and characterizing extracellular vesicles from cerebrospinal fluid and plasma. After comparing multiple approaches, size-exclusion chromatography emerged as the most effective method for achieving EV purity and recovery. The team also developed a scalable, cost-effective custom method for EV isolation and began developing approaches for selectively capturing neuron-derived EVs.
Perhaps most significantly, the team developed highly sensitive methods for measuring the HTT CAG repeat in extremely small amounts of DNA. Using optimized extraction, amplification, fragment analysis, and PacBio long-read sequencing, the investigators successfully measured CAG repeat lengths from CSF samples containing as little as 0.001–0.01 ng of DNA.
The findings revealed substantially greater somatic CAG expansion in CSF than in matched plasma samples, including alleles exceeding 300 CAG repeats. Importantly, the CAG repeat distributions observed in CSF resembled those observed in brain tissue, while blood and dura showed substantially less expansion. These results provide evidence that CSF extracellular vesicles may provide a meaningful window into molecular events occurring within the central nervous system.
The project also produced validated digital PCR assays for HTT, HTT1a, MSH3, FAN1, and neuronal markers and demonstrated that HTT1a production increases with CAG repeat length and is particularly elevated in differentiated neuronal cells.
Together, these advances establish an important foundation for developing minimally invasive biomarkers that could eventually be used to monitor disease progression or evaluate therapeutic response in clinical trials.
Building a Translational Research Network
The project has also generated an unusually broad collaborative network spanning clinical research, neurogenetics, extracellular-vesicle biology, proteomics, neurodegeneration, and industry.
Collaborators include investigators at UCL, the University of Cambridge, the University of Oxford, UCL/Birkbeck, the University of Hamburg, Harvard's Wyss Institute, Evotec, Ionis Pharmaceuticals, CHDI Foundation, and major brain-bank resources. These collaborations provide access to patient cohorts, specialized technologies, therapeutic compounds, proteomic capabilities, and postmortem tissue.
The breadth of this network demonstrates how a relatively small pilot award can serve as a catalyst for a much larger translational research effort.
Follow-on Funding
Dr. Flower's project provides a clear example of the financial leverage created by an MDF pilot award.
The preliminary data generated through the MDF-supported research directly enabled applications for substantially larger grants, including:
- HDF Transformative Research Award: $500,000 per year for two years, submitted in March 2025, to support clinical validation of EV-based biomarkers.
- UK DRI–LifeArc Translation Pilot Award: £50,000, awarded, supporting optimization of repeat-instability and transcript-quantification assays.
- CHDI Academic Fellowship: $850,000 over two years, awarded, supporting long-read sequencing, digital PCR, EV profiling, mechanistic studies, and therapeutic experiments.
Thus, the MDF investment helped generate the proof-of-concept data necessary to compete successfully for more than $1.8 million in subsequent major research funding, in addition to the £50,000 UK award.
Advancing the Investigator's Career
Dr. Flower described the MDF award as having a "transformative impact" on his research trajectory. The funding provided the resources and protected time needed to establish an independent research program focused on minimally invasive biomarkers for Huntington's disease—an area that he described as previously inaccessible because of technical limitations and the difficulty of obtaining funding for high-risk pilot work.
The award enabled him to generate the foundational data necessary to compete successfully for major subsequent funding and helped establish his research group as a translational hub integrating molecular measurements from patient biofluids with disease staging and therapeutic monitoring.
The work now provides a foundation for future clinical-trial biomarker development and positions Dr. Flower's group to contribute to the development of molecular tools for evaluating disease progression and therapeutic response.
In 2024, the Movement Disorders Foundation announced its inaugural round of Young Investigator Pilot Grants. Recipients included Michael Flower, MD, PhD, Senior Clinical Research Fellow and Consultant Academic Neurologist at the University College London Institute of Neurology and National Hospital for Neurology.
To be eligible for consideration, Dr. Flower was required to address specific applicability to Huntington’s disease in his research project: CSF biomarkers for somatic instability and treatment efficacy, as well as one other movement disorder, and demonstrate the potential to facilitate rapid translation to clinically useful therapies.
View the video to learn about Dr. Flower's project. Click below to read Dr. Flower's research proposal.