Brain Games

Courtesy Photo | Illustration of the blood-brain barrier (BBB). The BBB is highly selective and allows certain large molecules, such as insulin, and small molecules, such as glucose, to pass through; but it may also inadvertently allow undesirable heavy metals into the brain’s environment, which at high enough concentrations can cause damage to the nervous system. (National Institutes of Health Medical Arts image)  

FT. BELVOIR, VA, UNITED STATES

07.29.2022

Courtesy Story

Defense Threat Reduction Agency's Chemical and Biological Technologies Department

Researchers are investigating methods to deliver life-saving pharmaceuticals through the brain’s selective barrier.

Chemical defense researchers are working on a way to deliver effective pharmaceuticals across the blood-brain barrier (BBB) that protects the brain and spinal cord of the central nervous system (CNS) to combat the serious threat that chemical warfare agents (CWAs) pose to the Joint Force. The BBB is a selective gate-keeper to the brain and spinal cord that allows useful small molecules like glucose to cross into the CNS while protecting it from some harmful toxins, bacteria, and viruses that can circulate through the rest of the body.

Organophosphate nerve agents (OPNAs), such as soman and sarin, and organophosphate (OP) pesticide poisoning cause severe symptoms throughout the human body, including those represented by the acronym SLUDGE: salivation, lacrimation (tears), urination, defecation, gastrointestinal upset, and emesis (vomiting). Many of the most serious symptoms are a result of OPNAs and OP pesticides blocking the function of acetylcholinesterase (AChE), which is a critical enzyme that is responsible for recycling and breaking down the neurotransmitter acetylcholine.

A neurotransmitter is a chemical released by nerve cells to transmit signals to other nerve cells. When OPNAs or OP pesticides render AChE dysfunctional, acetylcholine builds up to dangerously high levels and results in cholinergic crisis exhibiting the SLUDGE symptoms. The overstimulation in the synapses between neurons in the brain and CNS disrupts other neurotransmitters and ultimately causes severe seizures and even death if left untreated.

The current standard of care for OPNA/OP poisoning includes a pharmaceutical called pralidoxime or 2 PAM, which is effective peripherally in the body—meaning it acts everywhere except in the CNS. As an AChE reactivator, 2-PAM reverses the chemical damage of the AChE enzyme caused by the OPNA/OP pesticide poisoning and brings the acetylcholine down to its proper level.

The Defense Threat Reduction Agency’s (DTRA) Chemical and Biological Technologies Department in its role as the Joint Science and Technology Office (JSTO) for the Chemical and Biological Defense Program is investing in research at industry, academia, and government laboratories to apply a variety of approaches to deliver medical countermeasures (MCMs) across the BBB and into the CNS. One such effort is to possibly attach 2-PAM to a molecule known to be able to cross the barrier, such as glucose, as an effective treatment for OPNA/OP pesticide poisoning. There are MCMs that can cross the BBB, but they largely treat just the symptoms and do not eliminate or fully reverse the effects of the OPNA/OP pesticide poisoning as 2-PAM does.

DTRA JSTO is transforming CB science and technology to prepare for current chemical and biological threats and anticipate the emerging threats the Joint Force may face in the future. Recent advances in materials science and nanotechnology offer many opportunities to expand the ways that pharmaceuticals are delivered. New and advanced materials like nanomaterials and biomaterials can be used to stabilize drugs and vaccine formulations, as well as target them to different areas of the body. A relevant example: both of the messenger RNA (mRNA) vaccines approved for use in humans against COVID-19 would not have been successful without the nanoparticle formulation to encapsulate and protect the mRNA. (To read this article, see the link in the sidebar.)

DTRA-JSTO researchers across academic, industry, and government laboratories are working to apply a variety of different scientific nanotechnology and formulation approaches to deliver 2 PAM across the BBB and into the CNS:

• Date Taken: 07.29.2022
• Date Posted: 07.29.2022 16:41
• Story ID: 426157
• Location: FT. BELVOIR, VA, US