Behind Mount Sinai's New Personalized Medicine Institute

Education: MD (1986) Friedrich-Alexander Universität School of Medicine, Erlangen-Nuremberg, Germany; Research Fellowship (1993 - 1995) National Cancer Institute, National Institutes of Health; Clinical and Research Fellowship (1990 - 1993) Nephrology, Massachusetts General Hospital and Harvard Medical School; Residency (1987 - 1990) Internal Medicine, Cabrini Medical Center, New York.

 

 

The Mount Sinai Medical Center in New York will use a $12.5 million donation from a regional foundation to establish a research center to study personalized medicine, the hospital announced this week.

 

The funds for the project will come from the Andrea and Charles Bronfman Philanthropies to be used over a period of 10 years to start the Charles Bronfman Institute for Personalized Medicine, and “bridge the gap between genomics research and clinical patient care in the area of personalized medicine.”

 

The hospital said it plans to use the gift to start an institution-wide biobank and a translational biomedical informatics center, which will be the IPM’s core areas of focus. The grant will also go toward what will become a $30 million personalized medicine initiative.

 

In an interview with Pharmacogenomics Reporter, Erwin Bottinger, director of Mount Sinai’s Charles Bronfman Institute for Personalized Medicine, discussed four specific disease areas of focus for the institute’s research and announced the IPM’s goal to build a biobank of 50,000 donors by 2012.

 

 

The overall agenda is to transform a major academic medical center which is located in a large metropolitan area, and move towards application of personalized health care approaches. There are two parts to this. One is in the area of discovery, making discoveries, supporting discoveries that can lead to personalization of health care, be it disease prediction or disease treatment. The second aspect is delivery of personalized health care.

 

We already have a number of genetic-based tests, of which some are FDA approved. Others are not FDA approved but have been validated in a number of settings that have not yet achieved wide acceptance in the medical care community. One aspect of the personalized medicine program would be to accelerate the introduction of new genome-based molecular testing to clinical decision-making and drug prescription. …

 

We want to validate findings that are being published at an increasing pace from other centers and then be at the first wave of institutions where these findings are introduced into clinical application at a very large scale systematically throughout the clinical care operations.

 

 

IPM will focus on discovery of diagnostic markers. The paradigm is that the discovery of diagnostic markers puts a bridge into the molecular pathway. Based on analyses of other genes, encoding proteins in a particular molecular pathway, one can develop hypotheses for targeted drug discovery, for which we at Mount Sinai have the capability through our Institute of Experimental Therapeutics. And certainly, that will be a secondary goal of the personalized medicine initiative, to provide leads in identifying molecular pathways that might be important in certain complex diseases that can be exploited by targeted experimental therapeutics discovery approaches.

 

 

One highly publicized example would be of [Roche’s drug-metabolism in vitro diagnostic] AmpliChip. That would be one example where the diagnostic is available, and FDA approved, but the acceptance and the implementation of these approaches in clinical practice is still lagging behind. So one aspect of the institute would be to provide the resources, and inform and educate our colleagues on the clinical care side to accept, and embrace, and implement these new paradigms for dosing drugs that are metabolized through cytochrome P450.

 

 

You point to a very important problem in the area, and that is, ‘How can we rapidly put together a large enough multi-center trial that can have a shot at producing this data with confidence?’ Certainly, the institute would be in a position to either initiate with partners or participate with partners in such trials.

 

 

These are largely questions of policy. There are a number of issues that need to be addressed on the level of legislation and guidelines. For example, reimbursement policies are often based on standards that are accepted by Medicare. We have to embrace molecular tests that are predictive in nature, and [realize that] the traditional standards which are based on signs and symptoms of existing disease … may not be the right way to go with regard to assessing the effectiveness of new molecular testing.

 

Overall we are really looking at preventive medicine. Through early prediction we can accelerate early preventive approaches. [There are] more policy aspects that need to be considered here, where we need to move away from the currently applied standards … to standards where we base decisions about effectiveness much more on ‘What role do these tests have on disease prevention?’ These are really important questions but they will require a community-wide effort and discussion.

 

 

To name a few [that] we are currently considering, and which we will evaluate to focus on in terms of investing and program development, would be in the area of autoimmune disease, where we have an outstanding track record in inflammatory bowel disease [and] multiple sclerosis. We have ongoing genome-based research in these areas.

 

Other areas of focus would be in fibrotic conditions, where we have excellent programs in chronic liver disease. Here we can apply to our patient base molecular tests that have been reported to discriminate whether individuals that are affected by hepatitis C will have a progressive course of liver disease and require treatment, versus those who will not have a progressive course and will not require treatment.

 

The original report on such SNP profiles came from Celera-sponsored research. Mount Sinai was a participant in that work. We would like to work with companies such as Celera and others to take original reports of predictive SNP profiles into our patient populations and validate those findings and validate the utility of those markers for clinical decision-making.

 

In the context of fibrotic conditions we have outstanding strength in the area of chronic kidney disease. … In addition there is a strong program in pulmonary fibrosis. The concepts are that fibrotic conditions will have shared underlying genetic susceptibility factors and will have distinct patterns of genetic susceptibility which dictate the organ’s specific response to environmental stress.

 

Another area we are considering is neuropsychiatric disorders where we have ongoing efforts in autism, schizophrenia, and obsessive behaviors. Here our colleagues in psychiatry tell us that there are symptom domains that are shared by all these diseases, and there are symptom domains that are distinct and specific to each one of those disorders. It will be extremely important to identify the genetic basis for different manifestations and shared manifestations across these disorders.

 

One of the last areas we’re considering is the area of hematological malignancies. …

 

So with that there are four areas where we want to prioritize our efforts. That’s not to the exclusion of any other areas. These are planning stages. I think the institute would consider it a great success if we could in a period of three to four years have four or five robust clusters of application of personalized medicine approaches for research and disease management.

 

 

The Department of Genetics and Genomic Sciences at Mount Sinai has an outstanding track record of discovery disease genes for monogenic diseases, [and] has a strong basis in medical genetics in testing for early, childhood, gene-based disorders as well as genetic counseling. The department is the primary operator of those efforts and will remain in that position. …

 

Where the Institute of Personalized Medicine comes into play in a complementary way is that we can, in partnership with the large clinical departments, such as the department of medicine and the department of psychiatry … through the biobank and the translational biomedical informatics center efforts at the IPM, we can make large patient populations that are representative of our medical center accessible to genomic research.

 

Through biobank efforts we aim to recruit at least … 50,000 donors into a standardized DNA data bank effort over a four to five year period. This will be through the translational biomedical informatics program. So that biobank DNA data can be linked with the clinical information system, through the targeted efforts of the informatics program. The primary aspect here is that the institute, through its integration with the clinical departments, can make a large patient population available for genomic and pharmacogenomic research.