Exosomes: A New Way for Biologics to Cross the Blood-Brain Barrier

Biologics, Quality Testing

The blood brain barrier is notorious for blocking therapeutic biologics passage into the brain. Do exosomes offer an avenue around this problem?
Image Source: Wikimedia Commons user Kuebi

For a long time, the blood-brain barrier (BBB) has posed a significant hurdle for researchers seeking to develop therapeutics for neurological disorders. Because of its highly selective permeability, the BBB prevents large-molecule biologics and even the majority of small-molecule drugs from crossing over. As a result, many potentially beneficial diagnostic and therapeutic agents are unable to reach the brain.

Challenges Facing the Transport of Biologics across the Blood-Brain Barrier

Currently, the most common method used to bypass the BBB is direct injection. Unfortunately, this delivery mode poses several risks, including possible infection or the need to remove a piece of the skull in order to access the brain.1 It’s easy to understand why patients and caregivers would get nervous upon hearing this. While the risks associated with this form of delivery may be acceptable for serious neurodegenerative disorders like Huntington’s, their use for diseases like early stage Alzheimer’s seem less appropriate.

That’s where exosomes could play a role in the future. Exosomes are small vesicles that are naturally present in many body fluids such as blood, saliva, urine and cerebrospinal fluid.2 One of their main roles in the body is to ferry chemical messages between cells. In addition, they’ve been implicated in the delivery of genetic material from cell to cell. As a result, scientists have been looking at exosomes as a potential mode of transport across the BBB.

Using Exosomes to Ferry Biologics across the Blood-Brain Barrier

The results have been promising. In 2011, scientists engineered exosomes to contain an RNA sequence that switches off a gene implicated in Alzheimer’s disease. They then injected the RNA-containing exosomes intravenously into mice. Now this is where it gets exciting. Those exosomes later made their way across the blood-brain barrier, as demonstrated by a 60% decrease of the target protein in the brain, meaning that the RNA sequence successfully knocked out the gene in question.3

These findings suggest that the vesicles could be a viable way to transport RNA and protein-based biologics across the BBB. There’s still a lot of work to be done, however. For one, the research was conducted in mice, so several more steps must be taken before we can use exosomes in clinical trials and hopefully validate them as a viable transport vehicle for therapeutic biologics.

Future clinical trials also raise another question: the scalability of using exosomes as a delivery vehicle. The biggest difficulty with using biologics to target the brain has been getting them across the BBB in sufficient amounts to provide effective treatment. If exosomes are to serve as a viable transport vehicle, they need to be created in adequate amounts as well. But that introduces another issue: could synthetic exosomes be developed? A synthetic version certainly could be manufactured more easily and in larger amounts than a more labor-intensive in vitro counterpart, but it could also face more regulatory guidelines and safety hurdles to pass before widespread acceptance and adoption.

Regardless of which version wins out, companies developing biologics must comply with all manner of regulatory guidelines. In an increasingly competitive field, firms need to keep up the pace of innovation and development. Unfortunately, quality testing is the stage at which companies typically face a bottleneck. How can therapeutic biologics companies keep their release cycles short while simultaneously minimizing compliance risks?

That’s where the BIOVIA Quality Testing Solution can be helpful. By integrating directly with your firm’s existing infrastructure, it replaces paper-based systems, thereby eliminating potential errors. Among its features include automated transfer of sample information and results, documentation of analytical test methods and SOPs, electronic data reviews and advanced reporting. Not only does it offer increased regulatory compliance as a result, the solution minimizes costs, improves productivity and most important of all, reduces quality testing cycles.

While there’s been lots of research into various ways to treat neurological disorders, finding methods to cross the BBB has presented one of the biggest obstacles. If exosomes become the preferred mode of therapeutic biologics delivery to the brain, it’s likely that companies will need to decide which type to pursue: in vitro vesicles developed from the patient’s cells or synthetic ones. Regardless of which one they choose for their neurological drug delivery, quality testing and quality control will remain a top concern. Contact us today to learn more about the BIOVIA Quality Testing Solution.

  1. “No place like exosome,” April 7, 2001, http://www.nature.com/scibx/journal/v4/n14/full/scibx.2011.386.html
  2. “Exosomes: an opportunity for a new class of biologic therapies,” August 21, 2015, http://nextbigfuture.com/2015/08/exosomes-opportunity-for-new-class-of.html
  3.  “New method delivers Alzheimer’s drug to the brain,” April 5, 2011, http://www.sciencedaily.com/releases/2011/04/110405124546.htm

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