The Future Direction of Dermatologic Therapy

VOLUME: 13 PUBLICATION DATE: Jan 15 2005
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Could this new discovery be a substitute for embryonic stem cells?

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Scientists are excited about a discovery that may end the controversial quest to use embryonic stem cells in cell replacement therapy.
As you probably are aware, embryonic stem cells have the unique ability to transform into many types of cells in the body, but when these cells are used in cell replacement therapy the embryos are destroyed as a result.
But now, according to new research published in Developmental Dynamics, scientists have found that a type of embryonic stem cell, known as a neural crest stem cell may be used instead of embryonic stem cells in cell replacement therapy.
Neural crest stem cells, which are found in hair follicles in adults, offer several advantages over embryonic stem cells. First, they can transform into many diverse types of cells. Second, they’re easily accessible in adult skin. Third, a patient’s own neural crest cells can be used for cell therapy, avoiding implant rejection.
Research has a long way to go, but studies in mouse models show that these cells can transform into neurons, nerve supporting cells, cartilage and bone cells, smooth muscle cells and pigment cells.

The future of dermatology research

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Dermatology research is alive and well in a state-of-the art research and development center that has recently been completed by Galderma in Sophia-Antipolis in southeast France.
Not only does the center offer breathtaking views of mountains and sea, but the research center houses the world’s largest R&D program that is dedicated to dermatology. It is here that a highly complex system of molecular discovery and testing is carried out.
To give you an example of the facility’s capacity: in 2000, the molecular library housed about 3,000 molecules gleaned mostly from high-throughput chemistry performed at the facility (a small portion of this total came from purchased molecules). At the end of 2003, the number of molecules in the library had jumped to 100,000.
The facility’s capacity to screen molecules has also increased dramatically. In 2001, before the new R&D facility was built, scientists at the Sophia-Antipolis location could screen 5,000 molecules during one testing round. By 2003, that number was up to 800,000. This efficient molecular screening process has enabled Galderma to increase its patents from about three a year in 1999 to 35 patents in 2004.

Issue Number: 
1_2005
author: 
By Robert A. Norman, D.O., M.P.H.

I generally start any of my writing in response to questions I ask myself. And I asked myself many questions when I pondered the future of the skin. Upon reflecting on the needs of my patients and others, dozens of possibilities arose from the myriad images, smells, touch and sounds that had filled my head from patient interactions over the years.
Although I began my inquiry with the more utilitarian potential of future skin developments, I decided to veer from the typical and explore some of the more futuristic and far-out roles of the skin.

For example, given the enormous influence of aesthetics among Homo sapiens, what about skin as entertainment? What about the skin as a vehicle for delivery of other drugs besides creams and ointments? How about providing a built-in protection for those with a heightened need for sun protection, such as those unfortunate souls with the dramatic disease xeroderma pigmentosa? Or, what about a way to use skin as a safeguard for the mild fair-haired red-eyed lass?

What if one could change skin colors based on mood? I knew of many patients with frustrating blush disorders who had wished their state of mind would not be so readily visible on their hot-red skin. However, others may want a change in color, such as a military person who is trying to hide from an approaching enemy. And of course there will be those who suffer a certain ennui from their current display of tattoos, and an ever-changing tableaux would offer an extensive realm of show-and-tell.

What Will the Future Hold for Dermatology?
What will be the new detection options? What will be the new treatment options? What will be the new educational and patient teaching options? How will ethics and patient selection
be challenged? How will integrative therapies and cosmetic surgeries evolve? Skin diseases can be expensive and time-consuming and affect self-esteem, personal relationships, and careers. They also have health implications — predisposing individuals to infection, scarring and other diseases.

As immunosuppressive and laser research are still in their infancies, the future of these fields appears boundless with new therapies constantly in development. Obviously, the continuous appearance of new treatments necessitates the regular update and revision of a physician’s standard practice methods.

Dermatological concerns are among the most common consults physicians and pharmacists get if you consider hair, skin and nails. Therapy in dermatology, particularly in the treatment of psoriasis and eczema, is changing significantly as new approaches to therapy reach the market and already-marketed products find new uses. As a result of the increased understanding of the molecular mechanisms of skin diseases, dozens of drugs are in Phase II or III trials. The “survivors” in this arduous contest will reach the market in the near future.

The Genetic Century
What new treatment options will we see for diseases such as xeroderma pigmentosum? The disease, characterized by defective DNA repair, affects young bearers of this autosomal-recessive disorder with severe solar damage and skin cancers, pigmented dry skin, and eye abnormalities. Patients who have this disorder have fought an uphill battle for many years. Incorporating bacterial repair enzyme T4 endonuclease V (T4N5) into a liposomal delivery vehicle and applying it to the skin results in markedly decreased skin damage.

With the virtual completion of the Human Genome Project mapping of 30,000 genes, genomic maps will be available to guide the efforts to determine the genetic basis of disease. We will be able to determine response to treatment and chart a person’s prognosis with greater efficiency. The Twenty First Century will be the “genetic century,” as scientists discover how specific gene mutations bring on skin disease, and we’ll be able to explore the multiple mechanisms surrounding the expression of these mutated genes.

With specific diseases such as melanoma, hope is on the horizon to replace traditional chemotherapy. Pills such as BAY 43-9006, a code-name, which should reach the market within 3 years, are a new generation of “targeted” therapies that are transforming the
treatment of horrible diseases such as melanoma.

The pill attacks the underlying molecular mechanism and will allow cancers to be treated as a chronic disease, such as high blood pressure, diabetes, or depression. Specifically, the new cancer drug attacks malignant tumors by blocking a chain reaction inside the cancer cells that allow them to multiply and attract blood vessels for growth.

New Skin
The skin is a marvel. In the best circumstances, it heals itself if broken down, repairing and restoring its former integrity. It is dour in sorrow, radiates warmth in love, and shines in tranquility. The skin is an organ in and of itself, with its own personality, temperament and particular eccentricities.

Its crucial body-covering role is becoming increasingly recognized, as well as the time it can use an outside boost. With almost every trauma, it rebounds. However, in burn victims who have lost more than 40% of their skin surface, a temporary cover by a meshwork of donor human skin or grafts is a lifesaver. The future will see the advent of even more lasting substitute, which will be critically needed. Likely candidates will include artificial matrices to grow skin from stem cells taken from the foreskins or umbilical cords of newborn infants. Others will use epidermal cells on an artificial dermis.

Other options are appearing, such as as a three-dimensional matrix composed of a combination of human skin cells and biodegradable polymers. The bilayered matrix acts as both a foundation and environment on which the dermal cells grow and shape. The porous under layer allows the in growth of human dermal cells and the outer layer, entirely synthetic, is designed as a barrier against infection, water loss, and ultraviolet light. The human dermal cells taken from neonatal foreskin are seeded and adhered onto the polymer matrix and allowed to incubate for several weeks. The cells multiply and organize themselves into functioning tissue and can be applied to replace damaged skin.

Chemically bonding collagen taken from animal tendons with glycosaminoglycan (GAG) molecules from animal cartilage to create a simple model of the extracellular matrix also may also provide a new dermis.

Teaching, Detection, Therapy and the Modern Era
What will be the new educational options in dermatology? I discussed this with Ben Barankin, M.D. He stated, “We will have virtual learning on the Internet with personalized medical histories and genetic tracking. As more physicians become computer and Internet savvy, and as the resources on the Internet improve, physicians will be able to sit down with patients and use their laptops to show patients images of their condition on dermatology atlas Web sites. In addition, they’ll be able to visually direct patients to patient support groups and other good resources of information.

Also, physicians will be able to take pictures of patients and give them a pre-op estimate of what their potential scars will look like following the procedure. The new computer systems will integrate digital photography, touch screens, voice recognition, and prescription downloads to pharmacies and HMOs to streamline patient interactions.

There will certainly be therapeutic options for those with genetic diseases. This likely will include oral forms of medication that dermatologists and medical geneticists will collaborate on in terms of developing custom-made therapies for patients. We’ll also see further developments in the treatment of skin cancers using creams. In addition, children will be vaccinated against a multitude of wart virus strains so as to prevent the viruses from developing.

As far as detection, there will be computers and robots that will perform full-body scans on a semi-annual basis and then compare changes in moles or other noteworthy external and internal developments. Physicians will be there to verify these findings, biopsy as necessary, and initiate treatment.

New devices to detect skin cancer and other skin maladies include image analysis and computer–assisted diagnosis, multispectral imaging and automated diagnosis, confocal laser microscopy, optical coherence tomography, ultrasound, MRI, spectrophotometric intracutaneous analysis, and artificial neural networks. Continuous research and refinement will allow improvements in detection and treatment.

Teledermatology (computer assisted, long-distance transmission of dermatological cases) will allow detection and therapeutic suggestions to areas where hands-on dermatology is limited. Dr. Joe Kvedar of Harvard Medical School writes, “Characterized as time-and place-independent care delivery, the exploding global computing network infrastructure (Internet) offers the opportunity for delivery of care anytime, anywhere. This care delivery method will enable dermatologists to offer services in a place-independent fashion and may interrupt current referral networks.”

Tania J. Phillips, M.D., Professor of Dermatology at the Boston University School of Medicine, stated, “I think teledermatology will play an increasing role, physician extenders will be increasingly used, and instruments such as the dermatoscope and other in vivo imaging techniques will be used. Treatments such as the immune response modifier molecules and biologics will be increasingly used for different indications. Hopefully, for wound patients there will be new, affordable cell-based therapies available. For education and teaching I think that the Internet and computer-based learning will supplant many of our traditional methods, as they are already doing.”

From an ethical standpoint, Internet-based “virtual details” on new products will become more common. Hopefully, less bias in prescribing based on personal influence from pharmaceutical companies and more objective, evidence-based data and research findings will result. Virtual details will help us to make our own decisions and not be influenced as much by the “drug reps” that wish us to sway our prescriptions writing choices towards their products.

What Else Is on the Horizon?
Long-lasting fillers are being studied that will more permanently repair defects. Face transplants are also coming — which are radical procedures intended for patients with severe disfigurement. Although doctors in the past have successfully reattached faces to patients after accidents, transferring facial tissue and blood vessels from a cadaver to a new patient has yet to happen. Although the transplant also brings a lifetime dependence on expensive immunosuppressant drugs to block rejection of the new tissue, the operation could offer an improved future for those who suffer severe burns, cancer or gunshot wounds. Of course, the procedure raises major moral, ethical and psychological issues.

Another development will aid in the delivery of medications. At the Georgia Institute of Technology, researchers have developed micro-thin implantable films that release medication according to changes in temperature. The device will allow patients to forgo daily injections and pills including insulin, hormone therapy, chemotherapy, biologics for psoriasis and other dermatological diseases, as well as other treatments.

Also, hair growth and transplantation will be safer and the individual, artificial-appearing hair plugs will be a historical reference. New and more individualized hair growth drugs will become available. Cloning of individual hair cells will allow an unlimited source of replacement hair.

Future of Dermatopathology
Mike Morgan, M.D., provided his reflections on the brave new world of dermatology and changes to be expected in diagnosis. “In the near term of the next 20 years, the dermatopathologist will continue to assume the primary responsibility of diagnosis although there will be changes in who reports the diagnosis and how it is accomplished. Increasing fiscal pressures exerted by third-party payers and Medicare debt will force the application of technologies such as telepathology, that were initially intended for improving medical care access, to be subverted under the pretext of cheaper medical care.

Familiarity with this concept by managed-care executives and its passive approval by dermatologists will eventuate in diagnosis performed by anonymous pathologists in offshore locations as has been recently witnessed in the radiologic field. Domestically, these technologies and the applied mantra of economies of scale could serve as a rationalization for centralization and a monopoly of diagnostic services by well-connected individuals or singular corporate entities. Ongoing scientific discoveries and the application of nascent technologies will however eventually lead to wholesale changes in the diagnosis and management of cutaneous disorders.

The dermatologist of the late 21st century will assume a greater degree of responsibility for diagnosis. Armed with hand-held spectrophotometric and chemical detection devices, the vast majority of cutaneous neoplasms will not only be accurately identified but
risk assessed in situ.

Characteristic light diffraction spectra will differentially fingerprint the types of cutaneous malignancy and the application of light or sound emitting devices will precisely gauge the depth of tumor penetration. Chemical detecting devices programmed to recognize subtle changes in the metabolic by-products of cancerous cells will complement the light-emitting devices. These devices will be relied upon to assess the extent of residual disease. Computerized algorithms that reconcile the measured variables of epidermal thickness, vascular density and depth of inflammatory infiltrate with pre-programmed archetypes will also permit the assessment and identification of many dermatoses.

Such advances will undoubtedly change the role of and importance of dermatopathology in the equation of dermatologic care. As they would be relegated to the arbitration of equivocal cases or sought in the assessment of confounding data or following incomplete response to therapy.”

Dermatology and Other Sciences
The future of integrative therapies in dermatology, such as preventive medicine, botanicals including antioxidants, hypnosis, and behavioral modification, will allow new detection and treatment options. Based on research in integrative medicine, new educational and patient teaching options will be utilized in dermatology.

Future scientific discoveries may demonstrate humoral connections for many dermatologic diseases that we have long suspected to be autoimmune. Through a mixture of good clinical observation and luck, we will make more connections. But, we must still discover whether these are an epiphenomena or actually a factor in disease formation.

We may soon look at the age of dermatological surgery for skin cancers with a healthy nostalgia when immune therapies and vaccines replace the need for these difficult, time consuming surgeries.

What about the future detective? We may have skin detective agencies utilizing bacteriological forensic techniques, pointing to individuals at the scene of a crime. Perhaps the characteristic microflora of a criminal suspect could be just as important to the detective as a
fingerprint or other genetic markers. If an individual’s microflora, established shortly after birth, remains comparatively constant throughout life, a microbial sampling of room dust, saliva and so on, might reveal groups of identifiable organisms which would match the pattern of a suspect. The particular manner of acquisition of the many different phage-types of bacteria from mother, hospital and early contacts could differentiate two suspects who would support different organisms. By sophisticated phage-typing methods, bacteria could be called to give evidence in court. The creation of a biochip that can be implanted into the skin of people to transmit their personal and medical information will be fodder for legal and scientific inquiry.

Gaining on the Battle
Perhaps the old adage about “what you don’t see can’t hurt you” applies. The huge majority or those critters that live on the skin are invisible and earn our indifference. And when it does bother us, at least we have treatments. As far as I know, we are the only species to have dermatologists, nail salons, beauty parlors and a myriad of other sources to rid our body of real or perceived ailments. Along with my fellow soldiers who fight these ever-lasting skin diseases, I know we can never win the battle.

However, when I think about the thousands of patients I treat with skin problems every year, I hope to provide solace from the onslaught of our own invaders. I’m glad I can provide a little help along the way and I’m looking forward to the future and what more we can offer.

References: 

References
1. Personal conversations/emails with Mike Morgan , MD, Lisa Hutchinson, PharmD, MPH, Ben Barankin, MD, David Elpern, MD, and Tania Phillips, MD.
2. Face transplants ‘possible within a year’ 15:05 27 November 02 NewScientist.com news service.
3. Teledermatology
http://www.emedicine.com/derm/topic527.htm
4. Norman R, “The Woman Who Lost Her Skin and Other Dermatologic Tales.”

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