Healight: A UVA light catheter that heals
Invented at Cedars-Sinai Hospital in Los Angeles, Healight is a novel technology with the potential to save countless lives and solve the problem of antibiotics resistance. Aytu Bioscience has the exclusive global licensing deal with Cedars-Sinai on all endotracheal and nasopharyngeal indications.
What is Healight?
Led by Mark Pimentel, MD, the research team of the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai has been developing the patent-pending Healight platform since 2016 and has produced a growing body of scientific evidence demonstrating pre-clinical safety and effectiveness of the technology as an antiviral and antibacterial treatment. The Healight technology employs proprietary methods of administering intermittent ultraviolet (UV) A light via a novel endotracheal medical device. Pre-clinical findings indicate the technology’s significant impact on eradicating a wide range of viruses and bacteria, inclusive of coronavirus. The data have been the basis of discussions with the FDA for a near-term path to enable human use for the potential treatment of coronavirus in intubated patients in the intensive care unit (ICU). Beyond the initial pursuit of a coronavirus ICU indication, additional data suggest broader clinical applications for the technology across a range of viral and bacterial pathogens. This includes bacteria implicated in ventilator associated pneumonia (VAP).
What is UV light?
Above is a diagram of the electromagnetic spectrum. This spectrum measures the entire range of light (or electromagnetic radiation). The waves on the far right are the weakest (radio waves for example) while the waves on the left are the strongest (gamma rays for example). In the middle, is the spectrum of light from 400nm to 700nm that we can see — we call this the visible light spectrum. You can think of this as a scale from high energy waves on the left, to low energy waves on the right. Directly to the left of the visible light spectrum, is the ultraviolet (UV) light spectrum, ranging from 100nm-400nm.
The image above may be familiar to some of you — it’s a diagram of the spectrum of light. As stated before, the UV light spectrum is 100–400nm. Based on what we just learned about the electromagnetic spectrum — we can see that UVC (100–280nm) is a higher energy wave, whereas UVA (315–400nm) is a lower energy wave. UVC light from the sun is almost entirely filtered out by the ozone layer, so very little of it every reaches our skin. UVC light can however be emitted from a light source — this is a technology that is used for sterilization in hospitals quite often. This high energy spectrum of light eliminates virus, bacteria, and fungi, but it is extremely dangerous if it is absorbed by human skin or eyes. Therefore UVC light is only used to sterilize rooms and equipment.
How does UV light kill bacteria and viruses?
It’s important to note that while there are quite a few working theories on this — there isn’t a concrete scientific consensus in all cases. We’ve reviewed as much data as we can find on the topic, so this explanation is based on the best evidence available.
One of the traits that bacteria, viruses, and human cells all share — is that they call contain DNA (or at least, RNA). DNA stands for deoxyribonucleic acid. In simple terms, DNA is two strands of building blocks connected together, and twisted into a double helix. These building blocks are called nucleotides — you can see them in the diagram, differentiated by which colour they are. There are 5 nucleotides — adenine, cytosine guanine, thymine, and uracil (only in RNA). Depending on the order in which these building blocks are arranged, they convey different information. A good comparison is to consider a recipe book. There are 26 letters in the alphabet, and when organized in the right order, they become the instructions for how to bake a cake. But what happens when you spill a drink on your recipe book? Part of the instructions are destroyed, if you still try and bake the cake, it will turn out all wrong. DNA works in the exact same way — the different nucleotides are arranged in a specific order, and they become instructions for creating proteins, repairing the cell, or even for cell-division itself. So what happens if the order of nucleotides is changed, or part of the instructions are destroyed? Just like the recipe that can no longer be made, the cellular processes can no longer continue. This is what UV light does, it damages the DNA or RNA in the cell, destroying the instruction manual that the cell needs to carry out all of its important functions.
To be more specific, as cited in the Healight pre-clinical data, it was noted that the working theory for this mechanism is that formation of pyrimidine(6–4)pyrimidone and cyclobutane pyrimidine dimers upon exposure to light disrupts microbial DNA and RNA, inhibiting replication. You can see in the image above a very simple example of this process, where the UV light causes a disruption to the nucleotides. Remember from earlier that UV light is just a form of electromagnetic radiation. This wavelength has enough power, to disrupt the nucleotide connections it comes into contact with.
Why doesn’t Healight damage human cells?
Once again, the answer is complicated. It might not be a fair statement at all in fact to suggest that Healight doesn’t damage human cells. More specifically though, so far it appears that the UVA light from Healight can damage viruses and bacteria much more effectively and much more quickly than human cells. This is why the Cedar Sinai team are confident they can treat patients in short intervals without significant risk.
To better understand why UV light is so damaging to bacteria and viruses, but not to human cells, it is important to understand the physical differences between these three cell types. There is a great deal of variation between different subcategories of bacteria, viruses, and human cells, but for the sake explanation we’ll take a look at some generic examples. On the next page are two diagrams that helps to explain the size difference between these organisms. One image has a measurement for each organism, while the other attempts to show you the true scale of the size difference.
This image depicts the sizes of various objects ranging from atoms on the far left, and a frog egg on the far right. More importantly though, this graphic has the sizes of a flu virus, a bacterium, and an animal cell. The left side of the graph is measured in nanometers (one billionth of a metre) and uses micrometers on the right (one millionth of a metre). The next graphic helps to put those numbers into perspective, showing the massive difference between the size of a red blood cell, an e. coli bacterium, and a common virus.
So, what’s the point? The point, is that there is evidence that the ability of UV light to penetrate the cell and to reach the DNA/RNA of the organism is dependent on the distance the light travels, as well as the medium it travels through. This concept is critically important for Healight. Typical bacterial cells are 1um in diameter, while the average human cell is 10–25um in diameter, and perhaps most importantly, Covid-19 is 0.125um in diameter. A study conducted by Columbia Medical Center on UV light penetration in various cellular models yielded some interesting results. It is important to take note that the wavelength of UV light they used is not the exact same as what will be emitted by Healight, so take the results with a grain of salt. The researchers concluded that the intensity of UV wavelengths of 200nm were reduced by half after penetrating only 0.3um of tissue, and wavelengths of 250nm were equally diminished after passing through 3um of tissue. So what does this mean? The researchers concluded that “It follows that ∼200-nm UV light can penetrate throughout typical bacteria, but cannot penetrate significantly beyond the outer perimeter of the cytoplasm of typical human cells — and will be drastically attenuated before reaching the human cell nucleus.”
To summarize in simple terms, their research indicates that UV light is able to penetrate bacteria and viruses significantly easier than human cells, as human cells are much larger, and the intensity of the UV light is severely diminished by the time it reaches the human cell’s DNA. It is important to keep in mind that this research was not conducted with the specific UVA light used by Cedar Sinai, however it is fair to assume that these principles will be relevant to Healight.
Is it possible that Healight will cause cancer?
Yes, it’s possible — but based on all of the data so far it seems extremely unlikely. The pre-clinical data exploring the viability of Healight, tested various human tissues and measured precancerious markers. These markers are reliable indicators that the damage leading to eventual cancer is taking place. Researchers measured levels of 8-hydroxy-2’-deoxyguanosineis (8-OHdG), a sensitive marker of oxidative DNA damage and oxidative stress, and at the conclusion of the study it is stated that exposure to NB-UVA did not increase the levels of 8-OHdG in cells treated with NB-UVA as compared to controls. More research is definitely needed in human models, but based on these tissue-based experiments, there is currently no indication that the UVA light from Healight will cause cancer. What is also important to note, as depicted in the graphic on the left, is that the human body has many defense mechanisms in place to help repair damaged DNA and prevent the host from developing cancer. The mechanism in this graphic illustrates the process of a photolyase repairing a DNA segment. The segment of the DNA strand represents a pyrimidine dimer created after the DNA is damaged by UV light. Photolyases are repair proteins that are activated by light, and they work to restore the DNA in your cells back to their original order. This is just one of many mechanisms that can protect the DNA in human cells from being permanently damaged by Healight.
Can Healight be used for more than just Covid-19?
Based on the pre-clinical data, UVA light appears to be highly effective on a wide range of bacteria and viruses. Below is a table listing various potential applications for Healight, based on information from the original Healight patent, as well as the pre-clinical data. Some of the more interesting applications will be covered in more detail later on.
Healight Future Applications
Below is a list of potential future applications of Healight.
Respiratory
- Used in ETT tubes of intubated patients to reduce viral and bacterial load
GI
- Treatment of ulcerative colitis and other inflammatory bowel diseases (IBD)
Urology/Nephrology
- Sterilizing blood during dialysis
- Sterilizing urinary catheters and reducing UTI incidence rates
- Treatment of bladder and urethral cancer
Surgical
- Improving treatment of abscesses by equipping drains with UVA light
- Accelerating anastomosis healing
- Reducing surgical adhesions
Cardiology
- Treatment of bacterial and fungal endocarditis
- Reduction of bacterial load in LVAD patients
Dentistry
- Treatment of gingivitis
- Treatment of submucosal oral cancers
Hematology/Oncology
- Treatment of intestinal graft vs host disease
Gynecology
- Treatment of bacterial vaginosis
- Treatment of submucosal cancers
Rheumatology
- Treatment of large joint arthritis
Neurosurgery
- Treatment of refractory meningitis
- Potential treatment for prion diseases
- Prevention of neural shunt infections
ENT
- Treatment of sinusitis and otitis
- Treatment of halitosis
- Treatment of mucosa and submucosal cancers
How soon can we expect Healight to progress?
Based on the information available from the FDA on their medical device approval process, we know that Healight will not follow a phase 1–4 progression as a vaccine would need to. Based on the information on the Cedar Sinai clinical trial page, we know that Healight has been classified as an “investigational device”.
This designation, is what allowed Healight to be used in the initial pilot study of the 5 patients. Not all medical devices require a clinical trial in order to be approved, but because of the novel and invasive nature of Healight, one is definitely required.
So how do we progress from here? Below is a graphic from Premier Research, showing a side by side example of the typical approval process for medical devices versus pharmaceuticals. If the results from the Healight pilot study are a success, we will move to the next arm of the study and test Healight on a larger patient population. As stated previously, this isn’t a process that all medical devices take, but because this is the first time UVA light is being used inside the human airway, the study process will need to be as strict as possible. When CEO of Aytu, Josh Disbrow, told investors during the Company’s November earnings call that they were considering a multicenter European study for Healight, this may be what he was talking about. With that being said, ever since Covid began the normal FDA approval timelines have changed significantly.
This leds us to believe Healight might be coming sooner than some may think. There are indications that viral load is reduced with Healight therapy but we have to wait for official PR from AYTU or Cedars-Sinai to confirm it.
More information will be added when new updates on Healight are available.
