Safety and efficacy of the UVLrx Treatment System
This therapy arises from dual origins. Firstly, from “Ultraviolet irradiation of blood” (UBI) and secondly from “Intravascular laser irradiation of blood” (ILIB).
UBI removed a small amount of blood from the body and irradiated it outside the body (extracorporeal) with UV light and then reinfused it into a vein. The UV source was broad-band and included UVC (200-280nm), UVB (280-320 nm) and UVA (320-400nm). A large fraction of the light was 254 nm (low pressure mercury lamp). Less than 5% of the blood volume was treated (and more usually 1-2%). Although the UV employed contained germicidal wavelengths (UVC), it is quite clear that killing some (or even all) pathogens in such a small fraction of the blood could not have any significant effect on the total burden of pathogens in the body. Nevertheless UBI had major effects on many different diseases both infectious in nature but also on noninfectious diseases (see literature survey). The possible mechanisms of action of UBI are discussed in detail in the attached reviews, but are almost certainly multi-factorial in nature.
ILIB involves the insertion of a laser fiber into a blood vessel and delivering various wavelengths of laser light directly into the blood-stream. The most common wavelengths lie in the red region (600-700 nm) but blue and green wavelengths have sometimes been used. The mechanism of action was never proposed to involve killing anything in the blood, rather that it relied on the known principles of photobiomodulation also known as “low-level laser therapy” or LLLT. These involve stimulation of mitochondria, modulation of reactive oxygen species, changes in intracellular calcium, and activation of transcription factors. As the light was delivered into the blood, and red cells lack mitochondria, it was proposed that platelets and other leukocytes (monocytes, neutrophils and lymphocytes) must have been involved.
Next we will address the question of safety. There has never been any question that the extremely low power levels of green or red light (0.32 mW/cm2@ 630 nm 0.27 mW/cm2 @ 530 nm) which are only a tiny fraction (<1%) of the power of daylight, can possibly cause any damage. Next we come to the UVA component, which we propose is harmless based on several lines of argument.
1. UVC (200-280 nm) is most damaging to DNA causing well-known photo-lesions (thymine dimers and 6,4 photoproducts) and accounting for its germicidal action. UVC is filtered out by the ozone layer and does not reach the earth’s surface.
2. UVB (280-320 nm) is ten times less damaging to DNA compared to UVC, but still causes photo-lesions. Nevertheless UVB is the main cause of UV-induced skin cancer and photoaging (since UVC does not exist on earth).
3. All living mammalian cells have developed very efficient DNA damage repair systems that work in combination with p53 to repair UV-induced DNA damage (or alternatively to eliminate the cell by triggering apoptosis if the damage is beyond repair). Studies have shown there is no detectable evidence of DNA damage remaining 48 hours after UV exposure.
4. The reason that prolonged exposure to UV from the sun can cause skin cancer is that basal cells in the epidermis which have characteristics of long-lived “stem cells” can suffer sub-lethal damage that slowly builds up over years of repeated sun exposure, until finally a basal cell carcinoma appears due to a “second hit”. Normal differentiated cells have a limited lifetime (days to weeks) so cannot build up this damage. There are only extremely rare “stem cells” existing in normal blood and they would never be exposed to repeated exposure to UV so the proposal that UVLrx Treatment could cause cancer is totally unrealistic.
5. UVA (320-400nm) does not damage DNA at all. Shorter wavelength UVA (320-350 nm) can interact with some proteins but only at comparatively high doses 10-50 times higher than contained in a UVLrx Treatment (1.20 mW/cm2@ 365 nm). The results of UVA on cells tends to be an increase in reactive oxygen species probably due to activation of NAD(P)H oxidase (NOX). Again repeated exposure of the skin to the sun over years is responsible for much of “photoaging” phenomenon (wrinkles and pigmented spots).
Department of Dermatology
Harvard Medical School BAR 414
Wellman Center for Photomedicine
Massachusetts General Hospital
40 Blossom Street
Boston MA 02114
Member of Affiliated Faculty of Harvard-MIT Division of Health Sciences and Technology
Effects of Light on Biological Systems
Light is therapeutic – a fact validated by countless clinical investigations conducted over decades. We know more about how light affects the body than some of our more common pharmaceutical agents. In some cases, the effects of light have shown to: reduce inflammation, modulate the immune system, improve ATP synthesis, reduce pain and improve wound healing (visible red light – 630nm), improve blood oxygen transport, circulation, wound healing and ATP synthesis (visible green light – 530nm), and improve ATP synthesis (UVA – 365nm).
Light’s effect on biological tissue stems from the activation of photo-sensitive molecules, referred to as photoreceptors. The molecular configuration of a photoreceptor is responsible for converting light energy into chemical energy. This can be as simple as light breaking a bond, which in turn, transforms a molecule from an immature state to an active one. From there, the activated molecule directly modulates the chemical behavior of all interconnected proteins and/or enzymes. The chain of events can quickly ripple throughout a cell or tissue. This is known as secondary transduction. Each newly activated or inhibited protein and/or enzyme will affect another, so on and so forth. This may continue to progress culminating with altered gene expression and cell metabolism and motility.
With the release of newly produced proteins and/or enzymes, the effect may extend far beyond the initially treated cell. For instance, light-induced protein and/or enzyme synthesis may further drive autocrine, paracrine, and endocrine communication. The latter, endocrine communication, defines the release of molecules directly into the circulatory system in which they are capable of traversing the entire body and influencing multiple organ systems.
However, like many other therapies, in order for light energy to influence affected cells, a very specific target must absorb the energy. Accordingly, researchers look at exactly what elements of a particular cell is capable of absorbing a specific wavelength. This is referred to as a cell’s or molecule’s absorption spectrum. The absorption spectrum of one cell may be unique to all other cells, enabling light therapy to stimulate an individual cell without impacting neighboring cells or tissue. Accordingly, use of well-defined light parameters represents an equally elegant solution to pharmaceutical agents to modulate a specific cell’s biology. Additionally, the combination of wavelengths could permit the activation of multiple photoreceptor molecules found within multiple cells to deliver a more comprehensive clinical response. This is important because a combination of pharmaceutical agents may pose substantial risk to the animal; therefore, a unilateral approach may be required.