Celltex Therapeutics has joined forces with Texas A&M Institute for Regenerative Medicine on a project that hopes to have a stem cell-derived therapy for Alzheimer’s in the clinic within three years.
Houston-based Celltex, which built its business as a stem cell bank allowing people to store their mesenchymal stem cells (MSCs) for later therapeutic use, is licensing intellectual property from the Institute on stem cell "exosomes," and the two organizations will work together on a multiyear research project led by Texas A&M professors Darwin Prockop, M.D., Ph.D., and Ashok Shetty, Ph.D.
Exosomes are small vesicles that split off from cells and are though to play a role in cell-to-cell communication, possibly used to transmit large molecules such as proteins and nucleic acids. MSC-derived exosomes have been explored as potential therapeutics for various diseases, with interest growing after the approach seemed to have a benefit in a mouse model of cardiovascular disease in 2010.
Since then, MSC-exosomes have been shown to help in other diseases and are now being touted as a potentially simpler way to harness MSCs than using the cells themselves, which can lead to regulatory challenges.
Stem cell transplantation therapy for a disease like Alzheimer’s is likely to be a tough call. There are many different neurons in the brain that are destroyed by the disease which "make each case unique and very difficult to treat," according to the EuroStemCell laboratory consortium.
To be successful, stem cells will have to delivered to the right areas of the brain, differentiate into the correct type of neuron and other supportive cells, and become "wired into" existing neural networks—all without causing serious side effects, it points out.
Exosomes won’t sidestep all these issues. However, being "cell-free" could make them easier to produce, work with, and deliver and—in principle at least—avoid potential toxicities such as cancer that are a perennial concern with stem cell therapies.
The collaboration between Celltex and Texas A&M will see Prockop’s team preparing adults' MSCs and using them to prepare MSC-exosomes with anti-inflammatory properties, while Shetty’s lab will focus on testing their ability to reduce brain inflammation, with the objective of being ready for human trials within three years.
The hope is that they will also assist in repair of neuronal damage related to Alzheimer’s disease, drawing on earlier experiments that have demonstrated how exosomes can reduce traumatic brain injury- and seizure-related damage to the brain.
“There are more than 5 million Americans living with Alzheimer’s,” Shetty said. “The best that drugs can do is conceal the cognitive and behavioral symptoms of Alzheimer’s in the short term, but they do not cure the underlying disease or halt its advancement.”
“We are hopeful that this research might someday treat the disease effectively by stopping or delaying the neuronal damage. Alternatively, exosomes may rejuvenate the networks of surviving but sick neurons via anti-inflammatory and neuroprotective effects.”