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THE MOSS REPORTS Newsletter (01/16/03)

 

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Ralph W. Moss, Ph.D. Weekly CancerDecisions.com

Newsletter #69 01/16/03

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Scientific American Lauds PDT

 

 

 

Photodynamic therapy (PDT) received a major boost with

a six-page feature article, " New Light on Medicine, " in

the January 2003 issue of Scientific American. Written

by Nick Lane, an honorary research fellow at University

College London, the article provides an excellent

overview of the therapy as it is currently being

applied in Western academic medicine.

 

 

PDT " has grown from an improbable treatment for cancer

in the 1970s, " says Lane, " to a sophisticated and

effective weapon against a diverse array of

malignancies today. " The article shows how PDT is now

also being used as a treatment for age-related macular

degeneration and pathologic myopia (two common causes

of blindness) as well as, experimentally, for coronary

artery disease, AIDS, autoimmune diseases,

transplantation rejection and leukemia. That is a tall

order, of course, but Lane makes a convincing case that

PDT offers hope for these conditions, and possibly

more.

 

 

As rs to this newsletter already know,

photodynamic therapy is based on the therapeutic

interaction of light, oxygen, and a photosensitizing

agent. Lane explains that the inspiration for PDT was a

result of research into porphyria, a rare blood

disorder characterized by extreme light sensitivity.

Individuals with porphyria accumulate high levels of a

natural chemical called porphyrin in their bloodstream.

When activated by light, these porphyrins can be

transformed into toxins that damage the skin, bones and

teeth. In extreme cases, the victim's lips and gums

erode to reveal red, fanglike teeth. Garlic can

exacerbate an attack, and, according to Lane, an early

folk remedy for the loss of hemoglobin (which contains

a porphyrin) may have been to drink blood. And so we have

all the elements of vampirism, as described by Bram Stoker

in his classic, Dracula.

 

 

In the mid-twentieth century scientists hypothesized

that the toxic effects of light-sensitive porphyrins

might be useful therapeutically. As Lane reports, they

made an extraordinary discovery: " If a porphyrin is

injected into diseased tissue, such as a cancerous

tumor, it can be activated by light to destroy that

tissue. " This was the origin of PDT as a cancer

therapy.

 

 

Lane calls the substances at the heart of PDT " among

the oldest and most important of all biological

molecules, because they orchestrate the two most

critical energy-generating processes in life:

photosynthesis and oxygen respiration. " The molecules

he is referring to, chlorophyll and hemoglobin, yield,

respectively, the " green " and " red " photosensitizing

agents in use today.

 

 

Lane gives a clear description of these molecules. All

porphyrins have in common a flat ring (composed of

carbon and nitrogen) with a central hole, which

provides space for a metal ion to bind to it. " When

aligned correctly in the grip of the porphyrin rings,

these metal atoms catalyze the most fundamental

energy-generating processes in biology, " says Lane. If

the central atom is iron, the molecule becomes

hemoglobin. If magnesium, it becomes chlorophyll.

(There is even a copper-centered porphyrin, called

hemocyanin, which gives the blood of horseshoe crabs a

blue tint.)

 

 

 

The Brokers of Destruction

 

 

 

Metal-free porphyrins become excited when they absorb

light at certain wavelengths and their electrons jump

into higher-energy orbitals. Says Lane, " The molecules

can then transmit their excitation to other molecules

having the right kind of bonds, especially oxygen, to

produce reactive singlet oxygen and other highly

reactive and destructive molecules known as free

radicals. "

 

 

Free radicals are thought of as uniformly undesirable.

However, if they are let loose inside a cancer cell,

the havoc they create can be used to achieve a

desirable effect: the death of the unwanted cell.

" Metal-free porphyrins are not the agents, but rather

the brokers, of destruction, " says Lane. " They catalyze

the production of toxic forms of oxygen. "

 

 

Lane recounts the early history of PDT, including the

pioneering work of Dr. Thomas Dougherty at Roswell Park

Cancer Institute in Buffalo, New York. Dr. Dougherty is

justly honored as the father of modern PDT. But as Lane

points out, there were problems with his famous drug,

Photofrin. First of all, Photofrin did not have a high

specificity to cancer. It also gathered in other

rapidly proliferating tissue, such as normal skin. As a

result of the heightened photosensitivity, nearly 40

percent of Dr. Dougherty's original patients developed

burns and skin rashes in the weeks after PDT.

 

 

More serious drawbacks emerged when other physicians

began trying their hand at PDT. In addition to their

lack of specificity, early PDT preparations suffered

from a lack of potency. These preparations were impure

mixtures of porphyrins that were " seldom strong enough

to kill the entire tumor. " Some were not very efficient

at passing energy to oxygen. Others were activated

" only by light that cannot penetrate more than a few

millimeters into the tumor. " Some natural pigments in

human tissues also blocked the absorption of porphyrin.

And sometimes the agent would accumulate in the

superficial layers of the tumor, absorbing all of the

light and preventing its penetration into the deeper

layers.

 

 

Since Dr. Dougherty's seminal paper appeared in the Journal

of the National Cancer Institute in 1975, many researchers

from different scientific disciplines have been working

to resolve these issues. Chemists have created new

synthetic porphyrins, especially from chlorophyll, with

greater selectivity and potency. These

" second-generation " agents are capable of being

activated at longer wavelengths to reach farther into

tissues and tumors. Physicists have designed new light

sources such as lasers and light-emitting diodes, or

LEDs, that can generate particular wavelengths to

activate porphyrins. Engineers have designed medical

instruments (such as endoscopes) to bring light to

deep-seated tumors. Pharmacologists have devised ways

to reduce photosensitive side effects by minimizing the

time that porphyrins spend circulating in the

bloodstream. Finally, says Lane, clinicians have

stepped in to design trials to " prove an effect and

determine the best treatment regimens. "

 

 

 

Searching for the Ideal Drug

 

 

 

" The ideal drug, " says Lane, " would be not only potent

and highly selective for tumors but also broken down

quickly into harmless compounds and excreted from the

body. " He gives a brief review of nine drugs that are

currently approved or in clinical trials: Levulan,

Photofrin, Visudyne, Metvix, PhotoPoint SnET2,

verteporphin, PhotoPoint MV9411, Antrin and Lutrin.

Each of these has its own strengths, of course, but (to

my knowledge, at least) none yet merits the status of

the " ideal drug " so aptly characterized by Lane.

 

 

The success of PDT for the treatment of macular

degeneration has inspired research activity in other

fields, but, according to Lane, " also reveals the

drawbacks of the treatment. " In particular, he claims,

even red light penetrates no more than a few

centimeters into biological tissue. " This limitation

threatens the utility of PDT in internal medicine --

its significance might seem to be skin deep. " (I

address this issue below.)

 

 

However, says Lane, " there are ways of turning PDT

inward. " One ingenious way is photoangioplasty, which

is being used experimentally to treat coronary artery

disease. Lane also discusses other potentially

promising uses of PDT, including the treatment of AIDS

and other autoimmune diseases and leukemias, as well as

to prevent organ rejection in transplant patients.

 

 

 

Giving Credit Where Credit Is Due

 

 

 

I have several comments to make about this excellent

article. First of all, though Lane rightly credits Dr.

Dougherty for his groundbreaking research, he fails to

mention the actual scientific founders of the field of

PDT, the medical student Otto Raab and his professor,

Hermann von Tappeiner, MD, of the Pharmacological

Institute of Ludwig-Maximillans University in Munich.

Raab and Tappeiner's work, first published in 1900,

preceded that of Dougherty by three quarters of a

century.These researchers are true scientific heroes

who deserve to be better known.

 

 

Second, and more importantly, I think Lane

underestimates the potential efficacy of PDT as a

treatment for deep-seated tumors. He repeats the

often-heard statement that red light penetrates " no

more than a few centimeters into biological tissues. "

However, as I mentioned in a previous newsletter, Harry

T. Whelan, MD, of the Medical College of Wisconsin and

NASA's Marshall Space Flight Center in Huntsville,

Alabama, has demonstrated the ability of light to

penetrate tissues to depths much greater than this.

 

 

In tests conducted on wrist flexor muscles in the

forearm and muscles in the calf of the leg, Dr. Whelan

writes, " most of the light photons at wavelengths

between 630-800 nm travel 23 cm through the surface

tissue and muscle between input and exit at the photon

detector. " This range of wavelengths (630-800 nm) is

precisely the range at which most commercial and

experimental photosensitizers now in use operate.

Twenty-three centimeters, the depth to which " most of

the light photons " penetrate, is more than nine inches.

 

 

Some readers may be disappointed that Lane makes no

mention of Cytoluminescent Therapy (CLT). It is not

surprising, however, since this revolutionary therapy

has emerged only within the last year. CLT represents

an improvement over conventional PDT in a number of

ways:

 

 

- It employs a non-toxic and highly cancer-specific

" green " photosensitizer called PhotoFlora, whose unique

properties need to grasped by the public and the

scientific community.

 

- It uses light as a treatment not just locally,

through lasers, but also systemically through

light-emitting diodes (LEDs) and infrared lamps.

 

- And, most importantly, it integrates PDT into the

broader context of complementary and alternative

medicine (CAM), with an emphasis on detoxification and

immune enhancement.

 

 

By focusing on the exciting developments in PDT, the

Scientific American article is acknowledging a growing

trend in oncology away from conventional cytotoxic

treatments and towards innovative approaches that are

highly selective for cancer. Although PDT is already

FDA-approved for some kinds of cancer, macular

degeneration and skin disease, it is still

underappreciated and underutilized. Scientific American

has been published continuously since 1845 and is among

the most influential journals in the world. This

article will serve as a wake-up call to scientific

opinion-makers worldwide that PDT has finally " arrived, "

while laying the foundation for even more exciting

discoveries and announcements in the months and years

to come.

 

 

 

--Ralph W. Moss, PhD

 

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References

 

 

Lane N. New light on medicine. Scientific American, January 2003.

http://www.sciam.com/article.cfm?colID=1 & articleID=000B4130-5C6C-1DF7-9733809EC5\

88EEDF

 

 

Dougherty TJ et al. Photoradiation therapy. II. Cure of animal

tumors with hematoporphyrin and light. J Natl Cancer Inst

1975;55:115-21.

 

 

Whelan HT et al. The NASA light-emitting diode medical program

-- Progress in space flight and terrestrial applications.

http://www.bioscanlight.com/word_3studies_i4_NN_343_21_eye1_56/the_nasa_light.ht\

m

 

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IMPORTANT DISCLAIMER

 

 

The news and other items in this newsletter are

intended for informational purposes only. Nothing in

this newsletter is intended to be a substitute for

professional medical advice.

 

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