Monthly Archives: November 2009

GINA swings into action

As of Saturday November 21, 2009, GINA entered the building.

Eighteen months after President Bush signed it into law, the Genetic Information Nondiscrimination Act of 2008  is officially effective.

GINA prohibits employer discrimination based on genetic information and also prohibits health insurers from denying coverage or setting rates based on a person’s genetic makeup, such as a predisposition to a disease.

This legislation is especially welcome and timely given the fact that we’re entering a new medical era in which our genomes will be increasingly explored to aid in diagnosis and treatment of disease, says James P. Evans M.D., Ph.D, Editor-in-Chief of the journal Genetics in Medicine and the Bryson Professor of Genetics and Medicine at UNC.

Dr. James P. Evans

“It is difficult enough to have to contend with a genetic disorder or disease predisposition without the added agony of worrying about what that knowledge might do to your ability to get insurance.”

Still, while a step in the right direction, GINA doesn’t afford any protection to individuals with regard to life insurance, disability or long term care insurance.

And unless comprehensive health reform  establishes requirements for insurers to offer coverage to all Americans who apply and prohibits them from denying coverage or charging more based on overall health, GINA does nothing to protect individuals from insurance discrimination once they have developed signs or symptoms of a genetic (or any other) disease.

Meanwhile,  GINA’s impact on genetic research subject recruitment remains unknown.  The government’s Office of Human Research Protections  offers an informational guidance on GINA implications for investigators and institutional review boards involved in HHS-funded genetic research.

But it remains to be seen whether or not people would be more likely now to participate in genetic research studies, to volunteer for genetic testing.

Les Lang

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Humanized mice and HIV prevention

An estimated 33 million people are now infected with HIV worldwide. But a not so small reason why AIDS has slipped from the top of the news is the general agreement among experts that an effective HIV vaccine could be many more years in the making.

The situation has led some researchers to study alternative preventive strategies, including pre-exposure prophylaxis with antiretroviral drugs.

One scientist whose work in this area is of special importance is  J. Victor Garcia-Martinez, Ph.D., professor of medicine, division of infectious diseases at UNC, and a member of the university’s Institute for Global Health and Infectious Diseases.

A newcomer this year to the Carolina campus, Garcia-Martinez  carries  a broad pallette of research areas: humanized mice, retrovirology, AIDS, stem cell biology, and human gene therapy.

J. Victor Garcia-Martinez, Ph.D.

Humanized mice? Yes, since their inception less than 20 years ago, mice carrying transplanted, functional human tissue, genes, cells or organs have been used experimentally as in vivo human  stand-ins in biomedical research.

Today, we have a number of humanized mouse models with reconstituted immune systems.  And it may well be that the best of the bunch for HIV/AIDS research is the so-called humanized bone marrow-liver-thymus (BLT) mouse   developed by Garcia-Martinez .

With immune systems reconstituted from human bone marrow, liver and thymus transplants, BLT are the model mice that come with all the goods necessary in one package to simulate immune system functions of  Homo sap.

Here are a few reasons why: BLT mice could provide a model for prevention of intravaginal HIV infection. In one study, they have been shown to be susceptible to HIV transmission via a single intravaginal exposure.

Intravaginal exposure of these mice to HIV led to systemic HIV infection coupled with a rapid loss of human CD4+ T cells from the gastrointestinal mucosa, a known  hallmark of acute HIV infection in humans.

In this same  study, vaginal HIV infection was prevented in the BLT mice by pre-exposure prophylaxis using a combination of antiretroviral agents.

And in another study led by Garcia-Martinez, BLT mice were shown to be susceptible to HIV infection after a single intrarectal inoculation. This, too, coupled with loss of  CD4+ T cells from gut-associated lymphoid tissue and other evidence “closely mimics those observed in HIV infected humans.”

You might say these studies go beyond proof-of-concept to powerfully demonstrate why Garcia-Martinez’s mouse model holds promise for the preclinical evaluation of microbicides and antiretroviral prophylaxis regimens against HIV.

Click here for more details on the man and his work. And check this blog for reports of new research.

Les Lang

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Predicting drugs’ side effects, new uses

Roth, Bryan MD, PhD

Bryan Roth, MD, PhD

It should come as no surprise that lots of target-specific drugs are no so targeted. After all, many of the most successful drugs on the market today are being prescribed for uses that are quite different from the ones they were originally designed to treat.

Sometimes serendipity in the form of unforeseen side effects happens. That’s how today’s Viagra avoided the pharmaceutical dustbin.  Having flunked a Phase 1 clinical trial as a heart drug for angina, researchers noted it was associated with penile erections. The rest is history, or herstory… whatever. 

Now, scientists at the UNC School of Medicine and the University of  California, San Francisco, have developed and tested a computational technique to predict a new drug’s side effects and new target diseases for existing drugs.

Their article published online November 1st in Nature, describes a “chemical similarity” approach using “statistics-based chemoinformatics” that compares drug targets by the similarity of their mutual binding partners, or ligands.

Co-senior study author Bryan Roth, M.D., Ph.D., professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC, says  “We may now have a way to predict what side effects are likely to occur from treatment before we even put a drug into clinical testing.” 

Read our news release here.

Les Lang

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