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A new avenue for Huntington therapy


A neuroscientist reports on Huntington disease results and a Nobel Prize reaction.

Neural transplants offer a new path to possible Huntington disease (HD) treatments. Experiments with an HD mouse model show that transplanting human neuronal cells delays HD symptoms and death in the mice. The results, published in Nature Communications, were from Steven A. Goldman’s group at the Center for Translational Neuromedicine, University of Rochester, and the Center of Basic and Translational Neuroscience, University of Copenhagen.

HD is an inherited neurodegenerative disorder characterized by loss of movement control, cognitive decline, and eventually death. HD currently has no cure. The disease causes deterioration of medium spiny neurons, which are abundant in the brain striatrum. When affected by HD, the neurons do not properly take up potassium, which is essential for nervous system signalling. The study by Goldman’s group did not focus directly on medium spiny neurons, though. The researchers worked on glial cells instead.

Why and how glial cells might protect against HD

Glial cells support the health and function of other neural cells so they are an obvious candidate for protecting or correcting defects in medium spiny neurons. Goldman and colleagues were the first to explore the effects of glial cells on HD development, though. The researchers generated human glial precursor cells with and without the genetic mutation that causes HD. They introduced these cells, at birth, into mice engineered to have HD and found that the human cells were incorporated into the brains of the chimeric mice.

The researchers then compared lifespan, learning ability, and motor performance of animals with HD and non-HD glial cells. They examined brain structure and measured signalling function of striatal neurons. On all tests, mice that received non-HD glial precursor cells were healthier than mice with HD glial cells—they had slower disease progression and lived longer. Additional experiments provided a possible explanation.

Mice with HD glial cells had too many potassium ions around the cells. The non-HD glial cells from the transplanted human cells maintained a normal potassium balance. These results point to glial cells as a possible target for HD therapy. “We’re progressing to preclinical assessment of glial progenitor cell transplants in different mouse models,” Goldman says. For example, his group is exploring transplanting the cells in adult rather than newborn mice. “Our priority is learning the therapeutic potential of the transplanted glial cells,” he says. NovoSeeds is supporting this early stage work.

An unexpected link to a Nobel-winning field

The HD study is one of several recent high-impact publications from the Goldman group. Another paper in an entirely different area brought them into a Nobel award-earning field. The 2016 Nobel Prize in Physiology or Medicine went to Professor Yoshinori Ohsumi for work on autophagy. This internal cell recycling process has implications for all of biology, including human disease. Goldman and his colleagues were collaborators on a study published in Cell Stem Cell that showed Zika virus, which can cause brain damage in a fetus if the mother is infected during pregnancy, inappropriately activates autophagy.

The Nobel Prize was “well deserved,” Goldman says. “Knowing about the pathway and the biologic process of autophagy has changed our conception of how cells age and what can go wrong in cell homeostasis.” Goldman’s primary interest is studying how nervous system stem and progenitor cells might be used for new therapies for neurological diseases. Every piece of information about how cells operate is valuable in that research. The autophagy work, he says, is a “spectacular observation, in terms of potentially modulating autophagy for therapeutic purposes.”

REFERENCE: Benraiss A, Wang S, Herrlinger S, Li X, Chandler-Militello D, Mauceri J, Burm HB, Toner M, Osipovitch M, Xu QJ, Ding F, Wang F, Kang N, Kang J, Curtin PC, Brunner D, Windrem MS, Munoz-Sanjuan I, Nedergaard M, Goldman SA. Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. 2016. Nature Communications 7:11758

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