Nanotechnology treatment reverses multiple sclerosis in mice
A nanotechnology treatment derived from bone marrow stem cells has reversed multiple sclerosis symptoms in mice and could eventually be used to help humans, according to a new study led by University of California, Irvine researchers.
“Until now, stem cell therapies for autoimmune and neurodegenerative diseases have produced mixed results in clinical trials, partly because we don’t know how the treatments work,” said corresponding author Weian Zhao, an associate professor of pharmaceutical sciences and biomedical engineering who is affiliated with the Sue & Bill Gross Stem Cell Research Center.
“This study helps unravel that mystery and paves the way for testing with human patients.”
In past experiments, intravenously injected stem cells – taken from bone marrow and activated with interferon gamma, an immune system protein – often got trapped in filter organs before reaching their target.
For this study, published in the journal ACS Nano, researchers avoided that problem by extracting nano-sized particles called exosomes from the stem cells and injecting them into rodents with MS.
Loaded with anti-inflammatory and neuroprotective RNA and protein molecules, the exosomes were able to slip through the blood-spinal cord barrier.
In addition to rejuvenating lost motor skills and decreasing nerve damage caused by MS, they normalized the subjects’ immune systems, something conventional drugs can’t do, said study co-lead author Reza Mohammadi, a UCI doctoral candidate in materials science & engineering.
More experiments are in the pipeline.
Loaded with anti-inflammatory and neuroprotective RNA and protein molecules, the exosomes were able to slip through the blood-spinal cord barrier.
In addition to rejuvenating lost motor skills and decreasing nerve damage caused by MS, they normalized the subjects’ immune systems, something conventional drugs can’t do, said study co-lead author Reza Mohammadi, a UCI doctoral candidate in materials science & engineering. The image is in the public domain.
“This novel treatment will be tested on humans in early 2020, initially on people with Type 1 diabetes,” said co-lead author Milad Riazifar, who worked on the study as a pharmacological sciences doctoral student in Zhao’s lab and is currently helping prepare for a City of Hope clinical trial of the method.
“If successful, it could pave the way for treating other autoimmune diseases, including multiple sclerosis.”
Other UCI researchers involved were Egest J. Pone, Aude I. Segaliny, Laura L. McIntyre, Ashley Hamamoto, Erika N. Calle, Wenbin Liao, Victor Pham, Jayapriya Jayaraman, Jonathan R.T. Lakey and Craig M. Walsh.
HSCT (Hematopoietic Stem Cell Transplantation) attempts to “reboot” the immune system, which is involved in damaging the brain and spinal cord in MS.
In HSCT for MS, hematopoietic (blood cell-producing) stem cells, which are derived from a person’s own “autologous” bone marrow, are collected and stored, and the rest of the individual’s immune cells are depleted by chemotherapy.
Then the stored hematopoietic stem cells are reintroduced to the body.
The new stem cells migrate to the bone marrow and over time reconstitute the immune system.
The Study: For this randomized, controlled clinical trial of HSCT in relapsing MS, investigators at Northwestern University (Chicago, Illinois), Sheffield Teaching Hospitals (Sheffield, England), University of Uppsala (Uppsala, Sweden), and University of São Paulo (Ribeirão Preto, Brazil) enrolled 110 people, 18 to 55 years of age, who had aggressive relapsing-remitting MS.
To be enrolled participants had to have experienced at least 2 relapses (or 1 relapse and MRI evidence of disease activity at a separate time) despite treatment with disease-modifying therapies (DMT) in the previous year. Individuals with less aggressive MS and those with progressive forms of MS were excluded from the study.
Fifty-five were randomly assigned to undergo HSCT, and 55 were randomly assigned to receive a different type or stronger DMT than the therapy they had taken the year before. A provision of the study allowed participants in the DMT group to receive HSCT if they experienced progression of disability after one year in the study.
The primary endpoint of the trial was sustained disease progression after at least 1 year, defined as a worsening of EDSS score of 1 point. The EDSS is a standard scale that measures physical disability. The professionals who measured participants’ EDSS were not aware of (blinded) their treatment group. The team also tracked safety, relapses and other outcomes.
Key Results: The study met its primary endpoint, with significantly fewer people in the HSCT group experiencing disease progression after 1 year compared to those in the DMT group: progression occurred in 3 out of 52 people in the HSCT group and in 34 out of 51 people in the DMT group. Progression increased over time, but significantly fewer progressed over time in the HSCT group compared to the DMT group.
In the first year, 1 person out of 51 experienced an MS relapse in the HSCT group, compared to 36 out of 52 in the DMT group. Significantly fewer experienced relapse over time in the HSCT group compared to the DMT group.
The HSCT group also showed significantly less disease activity on MRI scans at 1 year and showed improvement in scores on a scale measuring quality of life (Short Form 36). Those who underwent HSCT after being in the DMT group for one year generally tended to do well.
Funding: Support was provided by the National Institutes of Health, a National Institute of Neurological Disorders and Stroke training grant, an Otto W. Shaler Scholarship and France’s ARC Foundation for Cancer Research.
Thanks to Peter Zekert of the UC Irvine for submitting this news for inclusion.
Source:
UC Irvine
Media Contacts:
Weian Zhao – UC Irvine
Image Source:
The image is in the public domain.
Original Research: Open access
“Stem Cell-Derived Exosomes as Nanotherapeutics for Autoimmune and Neurodegenerative Disorders”. Milad Riazifar,
M. Rezaa Mohammadi, Egest J. Pone, Ashish Yeri, Cecilia Lässer, Aude I. Segaliny, Laura L. McIntyre, Ganesh Vilas Shelke, Elizabeth Hutchins, Ashley Hamamoto, Erika N. Calle, Rossella Crescitelli, Wenbin Liao, Victor Pham, Yanan Yin, Jayapriya Jayaraman, Jonathan R. T. Lakey, Craig M. Walsh, Kendall Van Keuren-Jensen, Jan Lotvall, Weian Zhao.
ACS Nano. doi:10.1021/acsnano.9b01004
