In mouse model of Friedreich's ataxia, a single infusion measurably restored normal cellular functions
Researchers at University of California San Diego School of Medicine report that a single infusion of wildtype hematopoietic stem and progenitor cells (HSPCs) into a mouse model of Friedreich's ataxia (FA) measurably halted cellular damage caused by the degenerative disease.
In this reconstituted schematic, hematopoietic stem cells (HSC) transplanted in a mouse model of Friedreich's ataxia differentiate into microglial cells (red) and transfer mitochondrial protein (green) to neurons (blue), preventing neurodegeneration.
Image courtesy of Stephanie Cherqui, UC San Diego School of Medicine
The findings, published online in the October 25 issue of Science Translational Medicine, suggest a potential therapeutic approach for a disease that currently is considered incurable.
Friedreich's ataxia is an inherited, degenerative neuromuscular disorder that initially impairs motor function, such as gait and coordination, but can lead to scoliosis, heart disease, vision loss and diabetes. Cognitive function is not affected. The disease is progressively debilitating, and ultimately requires full-time use of a wheelchair. One in 50,000 Americans has FA.
FA is caused by reduced expression of a mitochondrial protein called frataxin (FXN) due to a two mutated or abnormal copies of the FXN gene. In their study, Stephanie Cherqui, PhD, associate professor in the UC San Diego School of Medicine Department of Pediatrics, and colleagues used a transgenic mouse model that expresses two mutant human FXN transgenes, and exhibits the resulting progressive neurological degeneration and muscle weakness.
Human hematopoietic stem and progenitor cells (HSPCs), derived from bone marrow, have become a primary vehicle for efforts to replace or regenerate cells destroyed by a variety of diseases. Previous research by Cherqui and colleagues had shown that transplanting wildtype or normal mouse HSPCs resulted in long-term kidney, eye and thyroid preservation in a mouse model of cystinosis, another genetic disorder.
In this study, Cherqui's team transplanted wildtype HSPCs into an FA mouse model, reporting that the HSPCs engrafted and soon differentiated into macrophages in key regions of the mice's brain and spinal cord where they appeared to transfer wildtype FXN into deficient neurons and muscle cells.
"Transplantation of wildtype mouse HSPCs essentially rescued FA-impacted cells," said Cherqui, "Frataxin expression was restored. Mitochondrial function in the brains of the transgenic mice normalized, as did in the heart. There was also decreased skeletal muscle atrophy."
The scientists note that the mouse model is not perfect mirror of human FA. Disease progression is somewhat different and the precise pathology in mice is not fully known. However, Cherqui said the findings are encouraging and point toward a potential treatment for a disease that currently has none.
Co-authors include: Celine J. Rocca, Spencer M. Goodman, Jennifer N. Dulin, Joseph H. Haquang, Hya Gertsman, Jordan Blondelle, Janell L.M. Smith, and Charles J. Heyser, all at UC San Diego.
Disclosure: Stephanie Cherqui is cofounder, shareholder and a member of both the scientific board and board of directors of GenStem Therapeutics Inc. The terms of this arrangement have been reviewed and approved by the University of California San Diego in accordance with its conflict of interest policies.
Scott LaFee | EurekAlert!
Unique brain 'fingerprint' can predict drug effectiveness
11.07.2018 | McGill University
Direct conversion of non-neuronal cells into nerve cells
03.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
17.07.2018 | Life Sciences
17.07.2018 | Information Technology
17.07.2018 | Power and Electrical Engineering