RESULTS:
The Laura Fund was established in 1995 within the nationally renowned MS program at Oregon Health & Sciences University, the largest brain research community in the West and known for its cutting-edge brain science.
“The Laura Fund has been a significant force in advancing our work. We simply would not be where we are without its funding.”
Moving forward, we’re eager to review and fund ideas from all over the world and across different disciplines. The Fund is open to traditional medical research institutions and the business and technology sectors and is especially interested in projects rooted in collaboration, sharing, and rethinking existing research.
Here are some of the past and current projects the Fund has supported:
Legacy Projects
Development of drugs that protect mitochondria
(Team Leader: Michael Forte, PhD, OHSU Vollum Institute)
Mitochondria serve as cellular powerhouses by generating the chemical ATP, the key chemical energy supply of cells. A prevailing theory regarding progressive MS suggests that mitochondria in the brain and spinal cord may undergo impairment, contributing to the gradual degeneration of nerve fibers.
A team at OHSU proposed that an aberrant opening of part of the mitochondria (the permeability transition pore or PTP) occurs in MS, leading to mitochondrial dysfunction and reduction of their ability to produce ATP. Inhibiting this process could safeguard nerve fibers. The financial support from the Laura Fund enabled the team to demonstrate that genetic manipulation could prevent PTP opening, offering protective nerve fibers in a mouse model of MS.
Subsequently, NIH funding facilitated a small molecule development program, synthesizing drugs capable of inhibiting the pore in vitro. However, these drugs require further refinement to enhance their ability to penetrate the brain, a crucial step for ensuring their efficacy in protecting nerve fibers in MS.
Developing novel MRI methods for measuring brain mitochondrial impairment
(Team Leader: William Rooney, PhD, OHSU Advanced Imaging Research Center (AIRC)
The research team utilized a grant from the Laura Fund to acquire a specialized coil for the 7 Tesla magnet at AIRC. This particular coil enabled the team to quantify the ATP production by mitochondria within the brain. The findings demonstrated that individuals with MS exhibit abnormal and reduced ATP production compared to health controls. The application of this MRI technique now empowers the team to assess whether drugs designed to safeguard mitochondria can elevate ATP levels in the brains of individuals with MS.
Antioxidant therapy to reduce brain injury in MS
(Team Co-Leaders: Rebecca Spain, MD, and Vijayshree Yadav, MD, OHSU MS Center)
Support from The Laura Fund has facilitated the development of a natural antioxidant, lipoic acid, as a novel therapy for MS. Initial studies showed that lipoic acid was highly effective at treating a mouse model of MS. Subsequent studies determined the optimal dose of lipoic acid for humans. In a 2-year pilot trial, it was observed that lipoic acid dramatically reduced shrinkage of the brain in MS compared with placebo-treated patients. With funding from the Department of Veterans Affairs and the US and Canadian MS Societies, a multi-center trial of lipoic acid will be completed at the end of this year. It will be an essential milestone for The Laura Fund.
Thyroid-like drugs for promoting remyelination in MS
(Team Co-Leaders: Thomas Scanlan, Ph.D. and Dennis Bourdette, MD, OHSU Departments of Chemical Physiology and Biochemistry and Neurology)
A substantial initiative backed by the Laura Fund spearheaded the creation of thyroid-like drugs capable of breaching the blood-brain barrier, ensuring elevated drug levels in the brain. These drugs demonstrated the ability to stimulate remyelination in three distinct mouse models, marking the success of a two-year endeavor. The outcome yielded a collection of brain-permeable thyromimetic drugs. OHSU secured a patent for this approach as a potential treatment for MS and subsequently licensed the technology to Autobahn Therapeutics, a biotechnology company actively advancing the technology for eventual commercial implementation.
Current Projects
Investigating a novel molecule controlling myelin formation
(Team Leader: Swetha Murthy, PhD, OHSU Vollum Institute)
Dr. Murthy discovered a set of molecules that were sensitive to stretching cell surfaces. She and her colleagues proposed that one or more of these molecules would be important to the control of normal myelin formation in development and remyelination following demyelination in MS. Support from The Laura Fund allowed Dr. Murthy to gain valuable pilot data supporting her novel idea, which led to the team applying for grant support from the NIH. This project is ongoing.
Measuring remyelination following aerobic exercise in MS
(Team Leader: Lindsey Wooliscroft, MD, OHSU Department of Neurology)
Dr. Wooliscroft and her team are investigating the positive effects of aerobic exercise in people with MS and assessing whether aerobic exercise stimulates remyelination as measured by an electrophysiological test, somatosensory evoked potentials, and by MRI. She will complete her pilot trial in December and will submit for further NIH funding. Support from The Laura Fund was critical to moving this research forward.
Measuring small vessel abnormalities in MS
(Team Co-Leaders: Drs Elizabeth Silbermann, MD and David Huang, MD, Ph.D., OHSU Departments of Neurology and Ophthalmology, and William Rooney, PhD, OHSU AIRC)
One theory about progressive MS is that small blood vessel abnormalities in the brain cause chronic ischemia that accelerates neurodegeneration. The challenge has been to measure small vessel changes in the brain. Dr. Silbermann and her team use optical coherence angiography to assess small blood vessels in the retina of people with MS and compare these to normal adults. Using funding from The Laura Fund, she will compare the results in the retina with small vessel blood flow as assessed with a newly developed MRI technology at the AIRC. This project is ongoing.
Developing a method to measure “smoldering inflammation” in MS
(Team Leader: Matthew Brier, MD, PhD, Department of Neurology, Washington University in St. Louis)
“Smoldering inflammation” is believed to be part of the cause of progressive worsening in MS. Dr. Brier is using funding from The Laura Fund to study combining MRI and PET imaging to measure “smoldering inflammation” in MS and determine whether a commonly used MS therapy, ocrelizumab, alters the “smoldering inflammation” as a test of the paradigm. Developing an imaging technique for measuring “smoldering inflammation” is critical to developing novel therapies for progressive MS. This project is ongoing.
Measurement of brain-derived extracellular vesicles in blood to assess tissue damage and repair in MS
(Team Leader: Jennifer Linden, Ph.D., Brain and Mind Research Institute, Weill Cornell Medical College)
Extracellular vesicles (ECV) carrying proteins and genetic material are shed by various cells within the brain and appear in the blood. Dr. Linden’s research focuses on conducting genetic analyses on ECV derived from myelin–producing cells, oligodendrocytes, and neurons. The goal is to identify gene expressions within the ECV that correlate with injury and repair processes in patients with MS. If successful, ECV measurement could be used in early clinical trials of treatments that might promote repair in MS. Support provided by The Laura Fund is critical to the development of ECV testing as a biomarker for MS.