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Microglia are specialised immune cells in the brain<\/p>\n
Science Photo Library\/Alamy<\/p>\n<\/p>\n
Replacing the brain\u2019s immune cells halts the progression of a rare and deadly brain disorder called ALSP, short for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia. This is the first time the treatment, known as microglia<\/a> replacement therapy, has been tested in humans \u2013 and it lays the groundwork for future trials to treat other neurological conditions.<\/p>\n Numerous studies indicate that dysfunctional microglia \u2013 specialised immune cells in the brain \u2013 contribute to a range of neurological conditions, such as Alzheimer\u2019s<\/a> disease and schizophrenia<\/a>. With ALSP, people have mutations in a gene that encodes for a protein essential for these cells\u2019 survival, which results in fewer microglia and progressive cognitive decline. There is currently no cure for the fatal condition.<\/p>\n So Bo Peng<\/a> at Fudan University in China and his colleagues turned to an experimental treatment known as microglia replacement therapy. Previous research in rodents has shown that transplanted stem cells \u2013 which have the ability to develop into other cell types \u2013 can replace microglia. But the brain\u2019s existing microglia must be depleted in order for this to happen, so there is an opening for the new cells to migrate into the brain and transform into a microglia-like form. This can be done using drugs that inhibit a protein microglia depend on to survive.<\/p>\n Peng and his colleagues first tested this strategy in five mice with genetic mutations similar to those in ALSP. Because these mutations already affect the protein microglia rely on, the researchers didn\u2019t have to deplete the protein with drugs. The team then transplanted stem cells from healthy mice into the sick ones. After 14 months, the treated mice had about 85 per cent more microglia in their brains, on average, than six untreated rodents with the same mutations. Their motor function and memory also improved.<\/p>\n Encouraged by these results, the researchers next treated eight people with ALSP using stem cells from donors without the condition. Brain scans collected one and two years later were almost no different from those taken before the procedure. In contrast, four people with ALSP who didn\u2019t undergo treatment saw significant brain deterioration and lesioning over the same period. This suggests the microglia replacement therapy had halted the condition\u2019s progression.<\/p>\n At the start of the study, all of the participants took an exam that measures cognition on a 30-point scale, with lower scores indicating worse cognition. When they took the same test a year later, scores remained stable, on average, for those who underwent microglia replacement \u2013 and fell almost 10 points for those who hadn\u2019t.<\/p>\n These results suggest microglia replacement therapy is an effective treatment for ALSP. Yet because this is the first human trial, \u201cwe still don\u2019t know the potential side effects\u201d, says Peng. \u201cBut since this is a rapidly progressive fatal disease, the benefits may be much more important to consider than the potential side effects.\u201d<\/p>\n Chris Bennett<\/a> at the University of Pennsylvania points out that stem cell transplants have been used to treat neurological conditions for decades. \u201cIt is thought to be effective specifically due to microglia replacement,\u201d he says. In fact, the US Food and Drug Administration recently approved two similar therapies for two other rare brain conditions. \u201cThose prior studies didn\u2019t use this specific term, but did the same thing, for a different disease,\u201d says Bennett. \u201cSo I would describe this as a clever and wise use of [stem cell transplants], but that microglia replacement therapy by [stem cell transplant] has been done for decades.\u201d<\/p>\n Still, these results highlight the broader potential of microglia replacement therapy. Peng believes the approach could one day treat more common brain conditions. For instance, several genetic mutations that greatly increase the risk of Alzheimer\u2019s disease affect microglia. Replacing these cells with ones from people without such mutations could be a promising treatment for the condition.<\/p>\n Topics:<\/p>\n\n