Stem Cell Therapy as a Treatment for Lewy Body Dementia
Researchers here demonstrate a stem cell therapy that produces improvements in a mouse model for dementia with Lewy bodies, a common form of neurodegenerative condition in which the mechanisms and progression overlap with those of Parkinson's disease to some degree. This looks like a compensatory therapy, partially restoring some of the lapse in necessary function in the brain that occurs due to damage without actually addressing the damage itself. In that it is an incremental improvement in the present mainstream approach to therapies for age-related disease, but still cannot possibly be as effective as approaches that succeed in repairing the damage. In synucleinopathies like dementia with Lewy bodies, that most likely means the development of methods to safely clear alpha-synuclein aggregates from brain tissues:
Neural stem cells transplanted into damaged brain sites in mice dramatically improved both motor and cognitive impairments associated with dementia with Lewy bodies. DLB is the second-most common type of age-related dementia after Alzheimer's disease and is characterized by the accumulation of a protein called alpha-synuclein that collects into spherical masses called Lewy bodies - which also accumulate in related disorders, including Parkinson's disease. This pathology, in turn, impairs the normal function of neurons, leading to alterations in critical brain chemicals and neuronal communication and, eventually, to cell death.The researchers transplanted mouse neural stem cells into genetically modified mice exhibiting many of the key features of DLB. One month later, the mice were retested on a variety of behavioral tasks, and significant gains in both motor and cognitive function were observed. The researchers examined the effects of the stem cells on brain pathology and circuitry connecting neurons. They found that functional improvements required the production of a specific growth factor - called brain-derived neurotrophic factor - by neural stem cells. The team examined two of the key brain structures that become dysfunctional in DLB - dopamine- and glutamate-making neurons - to determine how BDNF might drive recovery. "Our experiments revealed that neural stem cells can enhance the function of both dopamine-and glutamate-producing neurons, coaxing the brain cells to connect and communicate more appropriately. This, in turn, facilitates the recovery of both motor and cognitive function."
To further confirm the importance of BDNF in these effects, the researchers modified the stem cells so that they could no longer produce the growth factor. When these modified cells were transplanted, they failed to improve behavioral function and no longer enhanced dopamine and glutamate signaling. Testing the possibility that BDNF alone might be an effective treatment, the researchers used a virus to deliver the growth factor to the brains of DLB mice. They found that this treatment resulted in good recovery of motor skills in the test rodents but only limited recovery of cognitive function. This suggests that while BDNF is critical to stem cell-mediated motor and cognitive recovery, it does not achieve this outcome alone.