By Jasmine Gill
This figure demonstrates that intranasally administered exosomes enter different regions of the brain and get incorporated into neurons and microglia.
Parkinson’s, Alzheimer’s, Multiple Sclerosis — diseases with no cure. However, this may not be the case in the distant future in part due to a Texas A&M University researcher and his study on status epilepticus, a condition where a single seizure lasts longer than 30 minutes.
Ashok K. Shetty, Ph.D., is this notable Texas A&M researcher. Originally from Karnataka, India, he received his doctorate from the All India Institute of Medical Sciences, New Delhi. After completing his education, he went on to be a professor at Duke University in North Carolina for 19 years.
“When Texas A&M started the Institute for Regenerative Medicine, they were looking for [an experienced neuroscientist],” says Shetty. “I was hired as the director of neurosciences.”
Now he is the associate director of Texas A&M College of Medicine’s Institute for Regenerative Medicine and a professor in the Department of Molecular and Cellular Medicine. There, he is testing the efficacy of cell and exosome therapy for brain repair.
“I’ve always been interested in the brain — very curious about how the brain [recovers] when it gets injured,” says Shetty. “My research has been focusing on brain repair after injury or disease. I have been involved in the development of cell therapy approaches for brain repair for a variety of neurological disorders such as Epilepsy and Traumatic Brain Injury.”
In the recent decade, the basic dogma of neuroscience has been refuted. “When I was an undergraduate student, we were taught that you had a certain number of neurons and that if they were injured [or lost], you would have [permanent] deficits,” says Shetty. “Now that is not the case — it is possible to regenerate neuronal precursor cells in the brain with the application of certain factors or the addition of new neurons from cultured stem cells.”
In 2017, Shetty published a paper where his team tested an improvised cell therapy approach involving the intranasal application of anti-inflammatory exosomes on a status epilepticus model.
This figure shows protection of neurons with intranasal administration of exosomes after status epilepticus
“Status epilepticus is a medical emergency,” says Shetty. “The longer the seizure, the greater the loss of neurons. The first focus of the doctor is to stop the seizure with antiepileptic drugs. When the patient goes to the ER, it stops the seizure [in most cases] but does not prevent it in the future. In the brain, certain changes are still happening, such as inflammation and swelling, which long-term can develop cognitive problems, depression, and chronic spontaneous seizures. This is why we need more than just antiepileptic drugs.”
In this study, the anti-inflammatory exosomes were extracted from adult mesenchymal stem cells and administered to mice after they were induced into a seizure for two hours, according to Shetty. The findings were significant.
There are certain proteins that cause inflammation and swelling in the brain get elevated after status epilepticus and can cause long-term brain damage. Findings showed that exosomes reduced the concentrations of these inflammatory proteins as well as reduced the loss of neurons. To top it off, intranasal administration of exosomes averted cognitive and memory impairments in the chronic phase. Essentially, the administration of anti-inflammatory exosomes significantly obstructed damage from occurring to the brain after the status epilepticus episode.
Although this research was done on status epilepticus, many other neurodegenerative diseases have a similar pathology.
“Many brain diseases have one common thing — brain inflammation from abnormal microglia activation,” says Shetty. “This is why we think this intranasal exosome approach can possibly help with other neurological diseases.”
Some of the diseases with similar pathologies include Alzheimer’s and Parkinson’s. Although there is still much progress to be made with additional testing, the promise of this new therapy can give hope to many individuals who suffer from different kinds of neurodegenerative diseases.
