Einstein's Clinical Sequencing Development Program Opens Doors to Clinical Insights for Bronx Patients

The idea of "personalized medicine," whereby individuals' own genes are used to direct their treatment, is extremely alluring; however, for most people, understanding the actual application to their own health remains unclear. This idea of tailoring healthcare to the individual patient has gained momentum throughout the medical community. "Personalized medicine is a concept that people are truly excited about, but we still need to demonstrate its feasibility" said Dr. Adam Levy, associate professor of clinical pediatrics.

Maria Delio, Dr. Cristina Montagna, Kunjan Patel, and Dr. Tom McDonald.Dr. Levy is one of the clinical investigators at Einstein and Montefiore Medical Center, the University Hospital for the College of Medicine, who are collaborating on genetic research with Dr. Cristina Montagna, associate professor of genetics and of pathology. Dr. Montagna and her research team established the "Clinical Sequencing Assay Development Program to Advance Personalized Medicine at Einstein-Montefiore."  Ultimately, when clinical tests are developed from what is learned in this research project, it will aid local clinicians with difficult diagnoses and enable them to better tailor their patients' treatments. "Our program brings together basic scientists and clinicians, the epitome of translational research," she said.

When a clinician has a patient for whom genetic testing is an option, he or she contacts Maria Delio, translational genetics manager of the project. Currently, the team has a list of conditions for which they are developing assays, and when a condition fits their research, sequencing is performed on the patient's samples. "If a mutation is detected, the samples are sent to a clinical lab for further validation, which includes the potential to offer a diagnosis that could help clinicians in determining appropriate treatment."

Dr. Montagna and Ms. Delio review some data"Information about patients is given to researchers at the bench, who in turn provide information back to the clinicians, who then share it with families as part of their diagnosis, bringing it all full circle," said Dr. Thomas McDonald, professor of medicine and of molecular pharmacology, who also has used the gene sequencing services in his cardiac research.

Both Drs. Levy and McDonald have partnered with Dr. Montagna in the hopes of providing answers to patients that they treat, particularly patients with rare and unusual disorders. These answers lie in the development of clinical sequencing assays, panels of genes that can be used to test samples of blood or tumor from a patient to identify the particular genetic mutation that is contributing to the patients' health problem.

In Dr. McDonald's case, the partnership has already begun to reap benefits for his patients in the Bronx. He noted, "One of our patients had been misdiagnosed multiple times in her childhood as a result of the seizures she was experiencing. By the time she came to us, she had been living with the wrong diagnosis for more than 12 years."

He continued, "Using the genetic testing panels developed with Dr. Montagna, we were finally able to correctly identify the mutations. After clinical testing for these mutations, we were able to diagnose and treat her. This diagnosis also helped to answer some lingering questions about her mother's death when the patient was a child, which we ultimately discovered related to a genetic condition that caused similar seizures in the patient. In addition, we were able to test her sister to determine that she didn't carry the mutation. As a result of that knowledge, she decided to have children, since she no longer was worried about the risk of passing on the mutation."

Dr. Adam LevyWhile the sequencing technology itself is relatively standard in the genetics field, Dr. Montagna's program is tailored to design genetic tests to specifically benefit local patients. "The Bronx has a very distinctive population, so the available gene panels used in commercial labs may not match our population," she said. "We have the opportunity to tailor these panels to our patient population and their specific genetics. The ability to correctly identify the mutations at work in a patient in an appropriate pathology lab will allow clinicians to choose the appropriate treatment for those patients."

In addition, says Dr. Montagna, "our program is unique because it includes a component to develop cutting-edge software tools to convey the genetic information to the physician and patient in a clear way, in keeping with the rules and regulations that surround genetic testing. We're fortunate at Einstein-Montefiore to have data analytics experts like Dr. Aaron Golden, associate professor of genetics, and Dr. Parsa Mirhaji, assistant professor of computational and systems biology, as well as director of Clinical Research Informatics, who can focus on this critically important aspect of making clinical sequencing ‘work' in practice."

"We've received great feedback from both clinicians and patients," said Ms. Delio. "Doctors are generally interested in this, in part, because of the ability to identify specific genes related to patient health issues. The patients are glad to learn why something is happening to them and whether it may also be a concern for other family members."

In the past, when clinicians had a suspicious finding, they sent the sample to a private commercial lab for sequencing. However, such testing is prohibitively expensive for most patients because it can require multiple rounds of testing and insurance companies do not typically provide reimbursement.

Dr. McDonald noted, "One of my patients experienced a lot of fainting in her teens and was referred to us after having two alternative diagnoses, one of which led to the implantation of a pacemaker-like device to shock her heart. When she came to us at age 20, her insurance company wouldn't cover commercial testing to identify her specific condition, so she was left with the option of presumptive treatment. Her primary care physicians also were unable to test her family. Through her participation in this research, we were able to identify two mutations and truly begin to treat her appropriately, as well as test the rest of her family to determine who else may be at risk for similar problems."

"The use of clinical sequencing assays can make the difference between knowing and not knowing, which can make a world of difference for our patients and the people treating them," said Dr. Montagna, "Knowing really opens up the possibility in the future for our clinicians to tailor the treatment to the specific needs of their patients."