Alzheimer’s is the most common cause of dementia. It gradually damages brain cells, leading to worsening problems with memory, thinking, communication and the ability to manage everyday life.
Placental Nanoparticles Travel Straight to the Brain’s Memory Center
Scientists are investigating an unconventional approach to fighting neurodegeneration by turning to the protective biological signals found during human pregnancy. A research collaboration involving Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario A. Menni Research Center of Fondazione Poliambulanza has developed an experimental nasal formulation utilizing extracellular vesicles.
These minuscule packages, naturally released by cells, carry proteins, fats and genetic instructions that cells can use to communicate with one another. Specifically, the team focused on a particular kind of MSC-derived EV – called human amniotic mesenchymal stromal cell-derived vesicles (hAMSC-EVs) – sourced from the placental amniotic membrane, the innermost layer of the sac that surrounds a developing baby during pregnancy.
When administered nasally to transgenic mice that had been genetically engineered to develop features of Alzheimer’s disease, the nanoparticles successfully crossed into the central nervous system. The mice received doses of the experimental spray twice a week for six months, from three months of age – at which point they hadn’t yet manifested Alzheimer’s-like symptoms – to nine months of age. Tests using fluorescent dyes confirmed that the hAMSC-EVs had reached all regions of the hippocampus, an area essential for learning and memory, and were co-localized with both neurons and microglia.
Reshaping the Brain’s Inflammatory Environment
Traditional Alzheimer’s research has heavily concentrated on two proteins linked to the disease, beta-amyloid and tau. Abnormal forms of these proteins can build up in the brain, but researchers increasingly believe that inflammation and changes in the environment surrounding brain cells also play important roles. Another factor implicated in cognitive decline is the chronic activation of specific cells in the brain – namely microglia and astrocytes – which can damage neurons through neuroinflammation.
In a new study reported in Translational Neurodegeneration, scientists may have found a way to help counter that inflammation, with help coming from what might seem like an unlikely source: the placenta.
“A particularly promising avenue within regenerative medicine involves harnessing the therapeutic potential of extracellular vesicles, particularly those isolated from mesenchymal stromal cells (MSCs),” the team writes in their paper, led by first author and cell biologist Andrea Papait.
“MSC-derived EVs (MSC-EVs) are nanoparticles that mediate intercellular communication and have been demonstrated to potentially deliver bioactive molecules with anti-inflammatory and neuroprotective properties.”
The investigators noted that the treatment appeared to influence several processes associated with Alzheimer’s disease. These included neuroinflammation and neuronal function, as well as the health of synapses, through which information is transmitted between nerve cells.
Cognitive Gains and Human Cell Testing
According to the researchers, these effects were associated with significant improvements in cognitive abilities. The vesicles appeared to prevent memory deficits from developing while also counteracting cognitive decline after it had already emerged.
To evaluate whether these animal model findings might translate to humans, researchers at the Fondazione Policlinico Universitario A. Gemelli IRCCS helped give the research a translational element. At its Memory Clinic, researchers collected skin biopsies from people with Alzheimer’s disease and healthy participants. The researchers also reported positive findings in experiments using human neurons grown in the laboratory.
Preclinical Realities and What Lies Ahead
While the non-invasive nasal delivery method offers an appealing avenue for targeting deep brain structures without invasive surgery, researchers emphasize that clinical application remains a distant horizon.
Claudio Grassi, senior researcher and neuroscientist
Future studies will need to determine safe human dosages, proper safety margins, and consistent efficacy before amniotic extracellular vesicles can emerge as a viable therapeutic strategy for halting neurodegeneration.
