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Next generation technologies promise to enhance treatment of disease


The implementation of next generation technologies coupled with the acquisition of a more in-depth knowledge of dermatologic diseases and conditions are proving to be very helpful in better treating and managing patients.


Istanbul - The implementation of next generation technologies coupled with the acquisition of a more in-depth knowledge of dermatologic diseases and conditions are proving to be very helpful in better treating and managing patients.

Next generation genome sequencing techniques allow clinicians to more quickly and accurately sequence a patient’s whole genome. According to one expert, these techniques are increasingly being implemented in dermatology to help characterize specific targets for new and evolving drugs potentially useful in numerous diseases and conditions such as melanoma, alopecia areata and vitiligo.

“The concept of these new whole genome sequencing techniques is to speed up the identification of relevant targets in the pathogenesis of a given disease. We can now sequence the whole genome in as little as one week and after finding the genes associated with the disease, we can then discern which gene is more relevant and then research optimal targets for the development of targeted drug therapy,” says Antonio Costanzo, M.D., associate professor of dermatology, Sapienza University of Rome, Italy. He spoke at the EADV Annual Congress, held here in October.

Melanoma treatments

A case in point would be cutaneous melanoma, Dr. Costanzo says, where researchers have discovered more than 70,000 mutations of the tumor, underscoring the great challenge in locating the relevant gene ideal for developing a targeted therapy. In sharp contrast, Dr. Costanzo says ocular melanoma has approximately 200 mutations, making it easier to develop a relevant targeted therapy. According to Dr. Costanzo, the next generation whole genome sequencing techniques are not only proving useful in dermatology but also in pharmacogenomics, where one can now study a patient’s response to a given drug.

“Using these techniques, we can now pre-genotype patients and see if there is a marker associated with a response to a given drug, or a marker of adverse events to that drug,” he says. “In the future, this will lead to a more accurate selection of the right drug for the right patient.”

Though the use of whole genome sequencing techniques for the identification of novel drug targets in cancer and the development of new drugs may come to fruition in a few years’ time, according to Dr. Costanzo, its application in pharmacogenomics to the existing drugs is immediate and is currently being readily used.

“Once you find out which genetic marker is associated to the response of a given drug, then you can immediately apply this to your patients. The reverberations of whole genome sequencing is being felt throughout medicine right now, and it is showing to be particularly useful in the identification of novel pathways and novel target genes to develop new drugs,” Dr. Costanzo says.


Applications in venereology

Some of the recent developments in venereology have been borne from continued research, which has resulted in a more in-depth knowledge of sexually transmitted diseases (STDs) and their appropriate therapies, as well as a sober analytical assessment of societal norms and shifts regarding sex and how to best help treat and manage patients with STDs. According to one expert, clinicians today have accrued a wealth of knowledge regarding STDs; however, one of the keys in better helping patients is to implement the knowledge gained.

“We currently have a vast knowledge down to the molecular level of many STDs including HIV (human immunodeficiency virus), human papilloma virus (HPV), syphilis, as well as other diseases,” says Derek Freedman, M.D., consultant Genito-Urinary physician, St. James’ Hospital, Dublin, and co-founding member of the European Academy of Dermatology and Venereology. “We know the epidemiology, we know the prevention and we know what works in terms of therapy; however, the implementation of this knowledge on the front lines is what will make the difference in our patients, now, and in the future.”

An “AIDS-free generation” is a recent aspiration put forth by PEPFAR (President’s Emergency Plan for AIDS Relief) in the United States, which Dr. Freedman says could be realized with the current wealth of knowledge regarding the disease. According to Dr. Freedman, PEPFAR provides an unprecedented $15 billion for the treatment of HIV-positive individuals in resource-challenged locations such as South and East Africa in the hopes of stemming the epidemic.

“We know that the transmission of HIV is related to viral load, and we have the ability to reduce the viral load to zero with appropriate treatment. Epidemiologically, if you reach the tipping point where the number of people on treatment is greater than the number of new infections, you could actually start to contain the epidemic,” Dr. Freedman says.

It is estimated that there will be about 40 million cases of HIV in 2016 and although the initiative of PEPFAR is a noble one, Dr. Freedman says that the funds provided will only be able to treat 15 million of those cases, meaning that about 25 million people will still need HIV treatment in the future.

“With the present level of funding, it is very difficult to see that impinging on the epidemic, underscoring the need for more funds and/or cheaper medications, as well as implementation of preventative measures,” Dr. Freedman says.

Simple preventative measures such as male circumcision are proving effective in helping to curb the acquisition of the disease in men. According to Dr. Freedman, recent study data presented this year at the annual STI & AIDS World Congress in Vienna showed that five years post adult male circumcision, the risk of acquisition of HIV could be reduced by 72 percent.


Addressing antibiotic resistance

Other preventative measures including anti-retroviral therapy administered either as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are also highly effective, Dr. Freedman says, and screening and treating for concurrent STDs such as syphilis, herpes and HPV can also help further reduce the risk of HIV acquisition.

The implementation of appropriate therapy for STDs, however, remains very challenging, Dr. Freedman says, most notably for Neisseria gonorrhoeae. The bacteria appear to have a relentless capacity to develop antibiotic resistances against many of the commonly used agents. Adding insult to injury, Dr. Freedman says, the bacteria commonly occurs in extra-genital sites such as the pharynx or rectum where other Neisseria species can be present, beckoning the need for more specific therapies and regimens in these cases.

In an attempt to better address the continuing issue of antibiotic resistances, the IUSTI (International Union against Sexually Transmitted Infections) recently put forth new guidelines on antibiotic regimens used for gonorrhea and other STDs. The suggestions stress the use of combination antimicrobial therapy such as ceftriaxone 500 mg and azithromycin 2 g. Newer combinations including gentamycin 240 mg IM and azithromycin 2 g, and gamifloxacin 320 mg with azithromycin 2 g are currently under investigation.

“The time for a single drug or single dose therapy appears to be over. Inappropriate prescriptions, inappropriate medications, over-prescribing and OTC (over-the-counter) prescribing likely all contribute to the current quagmire seen with antibiotic resistances. Hopefully, the suggested combination of drugs and their synergy will be useful in effectively treating these infections,” Dr. Freedman says.

Other developments in venereology include new and more affordable diagnostic systems such as multiplex NAAT (Nucleic Acid Amplification Testing) devices that can help diagnose an array of different pathogens from a single sample. Dr. Freedman says, however, that the specificity and sensitivity of some of these technologies and devices may be questionable and therefore, caution is warranted.

“Though many of the technological advances of late can be useful in detecting different pathogens, some of the current devices remain unproven. Having said that, we should not forget the sure-fire diagnostic potential of the microscope, as it is a cheap, economical, user-friendly diagnostic modality that in the majority of cases can provide an accurate and immediate point-of-care diagnosis,” Dr. Freedman says. “We should not forget the well-proven diagnostic methods of the past, as they are and remain very useful, effective and accessible.”

Disclosures: Drs. Costanzo and Freedman report no relevant financial interests.

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