Taking Disease "Personally": Columbia University's Precision Medicine Initiative

Anyone who has been to a doctor’s office knows that sitting in the waiting room before an appointment can be anxiety-inducing. We worry about the imminent diagnosis for what is ailing us, and fear we might hear words such as “incurable,” “degenerative,” or “irreversible.” We anticipate the possible range of conditions or diseases we may have, and the treatments we may have to undergo in search of a cure.

A new, personalized approach to medical treatment called “precision medicine” may change our way of thinking about disease and treatment options. Precision medicine suggests that the cure to a disease is not a generic, “one-size-fits-all” model, but rather, differs from person to person. The cure exists at the most basic, molecular level of your body: your genes. Precision medicine determines each individual’s “genetic profile” – his or her entire DNA code – and uses that data to identify the best course of treatment.

Since President Obama announced the launch of the Precision Medicine Initiative at the National Institutes of Health (NIH) during his 2015 State of the Union Address, there has been an overwhelming public response. Hundreds of articles have been published about the seemingly endless possibilities of precision medicine. A simple Google search of the phrase “precision medicine” yields over 83,200,000 results. Several large academic, research, and medical institutions around the country have started their own precision medicine initiatives. There seems to be a general consensus among the public that we are on the brink of something new, a revolution in medical treatment that may change the face of medicine as we know it.

Harnessing the power of genomic science, the NIH hopes to pioneer new ways of detecting human diseases and advancing “pharmacogenomics,” or the science of prescribing “the right drug for the right patient at the right dose.” Scientists at the NIH imagine genomic science radically altering our approach to disease treatment and management.

While Columbia University may not have been the first institution to call attention to genomic science, it has been at the forefront of the precision medicine movement for many years. To develop the university’s focus on genomic medicine further, Columbia University President Lee Bollinger recently   announced the formation of a university-wide task force on precision medicine. This task force aims to develop research into genomics and disease management as well as the cultural, legal, and political implications of this humanistic medicine.

The coalition will be comprised of approximately 40 members of the Columbia University community, including: the Trustees; the Columbia University Medical Center Board of Advisors; numerous faculty members; David Goldstein, Ph.D., the Director of the newly established Institute for Genomic Medicine at Columbia University Medical Center; and Lee Goldman, M.D., Chief Executive, Executive Vice President and Dean of the Faculties of Health Sciences and Medicine at the College of Physicians and Surgeons. “Human genomics is creating breathtaking new opportunities to understand the biology of disease and to provide more effective and more targeted therapies,” states Dr. Goldstein.

This multidisciplinary coalition will partner with NewYork-Presbyterian Hospital, the New York Genome Center, the New York Structural Biology Center, and the New York State Foundation for Stem Cell Research (NYSTEM) to form one of the most expansive initiatives within the precision medicine movement yet.

But what do genomic science and precision medicine have to do with ophthalmology and vision diseases?

The answer: everything. Stephen Tsang, M.D., Ph.D., the Laszlo T. Bito Associate Professor in the Departments of Ophthalmology and Pathology & Cell Biology, is one of several faculty members whose research attempts to answer that question on a daily basis. Scientists such as Dr. Tsang are exploring pathways into the genetic origins of disease in innovative and unprecedented ways. Using “induced pluripotent stem cells” (or “iPS cells”), Dr. Tsang is enhancing ophthalmic research into inherited and degenerative retinal diseases.

iPS cells are the functional equivalent of embryonic stem (ES) cells; once they are “reprogrammed,” iPS cells can develop into any type of cell and help to regenerate cells throughout the body. They provide a similar range of genetic diversity as ES cells and can demonstrate how gene mutations impact cellular development. They are also crucial in facilitating the testing of pharmaceutical drugs.

iPS cells are skin cells that are culled from individual patients. To collect iPS cells from patients, Dr. Tsang simply obtains a 2mm skin sample. In order to change the skin cells into iPS cells, he must “reprogram” the skin cells into “pluripotent” cells, or cells that are not fixed in terms of their developmental possibilities. The process requires manipulating the cell’s specific properties to ensure its transplantation will help regenerate cells anywhere it is used within the body.

Reprogramming the iPS cells allows Dr. Tsang to minimize the chance of cell rejection after transplantation. He remarks, “This is not a transplant in the traditional sense, in which an organ comes from another donor. You are not in danger of rejecting the donor cells; they are your own cells, taken from your body.” He continues, “All we have done is reprogram your cells in a way that provides the missing link that may cure whatever is ailing you.”

In one experiment, Dr. Tsang obtained iPS cells from two patients, each with retinitis pigmentosa (RP), a form of inherited blindness that affects 1.5 million people worldwide. RP has multiple genetic sources, but one of the gene mutations associated with the disease has an unknown function. Dr. Tsang studied this particular gene – known as “membrane frizzled-related protein” (MFRP) – and investigated the defects it creates in cells. To reverse these flaws, he collected iPS cells, made copies of them, and delivered the copies via gene therapy. In doing so, he managed to interfere with the process of gene mutation and discovered that the specific defects that MFRP triggers can actually be reversed. This finding was a major step forward in the treatment of vision diseases such as glaucoma, macular degeneration, retinal detachment, and retinopathy of prematurity. Patients suffering from these diseases could potentially benefit from the ability to regenerate ocular cells and tissues from iPS cells.

Dr. Tsang states that using iPS cells is like “having a patient-in-a-dish.” The culture dish is a more cost-effective and controlled space in which he can conduct experiments to test the success of gene therapy. The alternative, conducting these initial experiments in vivo, or in live patients, is expensive and often unreliable.

However, the process of generating new cells from iPS cells has not yet been perfected. Often, iPS cells fall short of their intended effect, becoming unresponsive or failing to mature as quickly as expected. Some researchers have proposed that it might take longer for iPS cells to mature in a dish rather than in the human body because the body is its own distinct system with specific signaling pathways and cues that stimulate cell growth. While it may take researchers years to find ways to accelerate the growth of iPS cells, these discoveries are remarkable breakthroughs that represent precision medicine’s potential to eliminate human diseases.

Precision medicine is no longer the science of the future; it is the science of today. It allows us to imagine a world in which glaucoma, cancer, heart disease, Alzheimer’s, or HIV/AIDS may no longer exist. However, reaching that point will require the close collaboration of scientists, government agencies, research institutions, philanthropists, and individual patients.

The progress scientists have made thus far is promising, but the next step is “capitalizing on these opportunities” and providing the collaborative support to potentially eliminate human diseases in the future, Dr. Goldstein states.

One thing, though, is certain: precision medicine proves that the cures to the diseases afflicting humanity have been living within us all along. We just need to unlock the remaining secrets of the human genome.