Why Bypassing the Blood-Brain Barrier Is So Difficult

The blood-brain barrier (BBB) poses one of the most significant obstacles to treating neurological disorders. While the BBB exists to protect the brain, it also shuts out many helpful medicines along with harmful substances. 

In the last three decades, there have been significant efforts to understand this shield-like barrier on the way to treating challenging diseases such as Alzheimer’s and Parkinson’s. Let’s take a closer look at why penetrating the blood-brain barrier is so difficult. 

Learning the Biology of the Blood-Brain Barrier


Before we can talk about getting past this barrier, it’s important to understand it. The blood-brain barrier (BBB) is a key security system of the central nervous system (CNS — the brain and spinal cord). 

Featuring a variety of cell types, the BBB acts as a functional and structural barricade to microorganisms and other external entities such as a number of biomolecules that are useful in systemic circulation but potentially harmful to the brain.

  • After almost 70 years of theorizing, scientists proved the existence of the BBB with the help of electron microscopy and cellular/biochemical research.1

In general, the BBB regulates and protects the microenvironment of the human brain.2

One important problem posed by the BBB is that it also prevents potentially beneficial drugs from entering the brain. 

Why is the blood-brain barrier so difficult to cross? This biochemical, physiological, and structural fortification adds dynamic layers of “armor” around the CNS. The blood-brain barrier acts like that shield, protecting the brain from intruders, but inevitably blocking out potentially beneficial molecules as well.

In a patient with head injuries, dementia, or Parkinson’s, this defense mechanism makes it hard to deliver what could be a life-extending or life-saving treatment. Unfortunately, research scientists and physicians have limited capability to deliver drugs past the BBB.3

The intricate biology of the blood-brain barrier makes its disruption challenging. Even fundamental factors such as sleep and wakefulness states may alter BBB function. Traditional medicine-delivery methods such as infusion, oral dosing, or standard nasal sprays have trouble penetrating the BBB effectively. In fact, it is estimated that only less than one percent of drugs considered for development are successful in getting past the BBB. 

Capillary endothelial cells (ECs), are an important BBB component. They are linked together by tight junctions that play a critical role in BBB maintenance and induction.4

Understanding Drug Delivery and Distribution in the Nervous System


The FDA has not yet approved a consistently effective delivery system for treating CNS disorders with drugs that are naturally blocked by the BBB.

Some molecules, such as oxygen, are capable of slipping past the tight junctions that connect endothelial cells in the BBB. Additionally, certain carrier proteins can escort specific molecules (such as glucose) past this barrier. Still, many large and small molecules — including critical medications — can’t get through. 

  • The involvement of the blood-brain barrier (BBB) is a key obstacle to getting adequate drug concentrations into brain tumors.5

So, how do we bypass the blood-brain barrier? Doctors at times use invasive tactics to treat the brain, such as intra-arterial delivery or direct surgical access (opening the skull and placing the drug in or on the tumor). Even then, these methods often produce lackluster results. Scientists have long been looking for less invasive and more effective methods to tackle this problem.6

How Kurve Is Helping


The brain is a delicate, vulnerable organ, susceptible to neurodevelopmental disorders (such as autism), neurodegenerative disorders (such as Alzheimer’s), as well as infection and physical trauma. In addressing these problems, getting through the BBB has persisted as a daunting challenge. 

The complex nature of the blood-brain barrier requires a new approach. Kurve has developed a technology platform to address this need. 

What started as a device to treat our CEO’s chronic sinusitis transformed into a technology with the potential to reshape the treatment of debilitating diseases such as Alzheimer’s. Our technology and specialty-drug formulations are designed to modify central nervous system diseases by delivering medication directly to the brain. We do this by crossing the BBB where it is unusually easy to penetrate — at the top of the nasal cavity, where the nerves for smell penetrate from the brain through the skull. In clinical studies, Kurve’s patented Controlled Particle Dispersion® (CPD) technology has been shown to bypass the blood-brain barrier and deliver significantly more medication to the brain than infusions. We are closer than ever to finding the “holy grail” of neurological disorder treatment.

With precise dosage control and innovative aerosol geometry, we can penetrate the blood-brain barrier and send drug formulations where they are needed. We are on a mission to turn the tide on cognitive aging and neurodegenerative disorders — but we can’t do it alone.

An investment in Kurve is an investment in the future of neurodegenerative diseases — one that is not so devastating. 

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