Making it Personal: Precision medicine may lead to important breakthroughs in treatments for neurologic disordersas long as concerns about privacy and data sharing are addressed

As a 13-year-old seventh grader, Charlie Blotner first began experiencing numbness and tingling in his legs and arms. His parents took him to numerous doctors and specialists, who suggested a simple case of teenage anxiety. When the tingling escalated from once or twice a month to multiple episodes a week, Blotner was finally referred to a neurologist, who scheduled an MRI scan. The result—a brain tumor—was a shock for his parents but something of a relief for Blotner. Finally someone believed he wasn’t making up his symptoms.

X MAN Charlie Blotne…
X MAN Charlie Blotne…

After five years of watchful waiting, Blotner underwent surgery to remove the tumor and agreed to donate some of the tissue to a research study at the University of California, San Francisco (UCSF). Investigators from UCSF and the Mayo Clinic are looking at gliomas, the most common type of malignant brain tumors, in adults to find better ways to understand and classify their genetic profile. The analysis showed that Blotner had a mutation in the IDH1 gene. Researchers do not fully understand how this mutation causes tumors, but they do know that the average survival time for adults with this mutation is 8.9 years post-diagnosis.

Blotner’s surgery was successful, but he knows he may be in a race against time to find a targeted treatment for his tumor should it return. It’s a race he may well win—thanks to an emerging field called precision medicine.

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Delivering the right treatment to the right person at the right time is the broad definition of precision medicine, a concept promoted by President Obama when he announced the creation of the Precision Medicine Initiative in his State of the Union address in 2015. Congress, with bipartisan support, passed the 21st Century Cures Act, which included $1.5 billion for this initiative. It was signed into law on December 13, 2016.

Physicians have always aspired to find the right treatment for patients, but precision medicine goes deeper, says Daniel H. Lowenstein, MD, professor of neurology at UCSF. “We recognize that each of us is unique at every level from our genomic makeup (the instruction set we inherit as genes), the molecules made in our genes, and the cell types, to the organs and our overall body, as well as our environmental exposures. Given all those factors, the goal of precision medicine is to come up with treatments for diseases that are as individualized as possible.”

Advances in technology—genomic sequencing, high-resolution imaging, more sophisticated tests, the ability to combine data across populations and the world, the computing power to analyze the data—add to researchers’ understanding of each individual’s makeup and help inform doctors on how to treat each person.

Until relatively recently, patients were placed into broad disease categories—breast cancer or lung cancer, for example. Today, thanks to genetic profiling, patients may be diagnosed with a more specific type of breast cancer such as HER2. Advances in biomarker tests help doctors and researchers identify and diagnose more rare diseases. And more precise diagnoses lead to more specific and customized treatments.

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Ten years ago, Santosh Kesari, MD, PhD, FAAN, professor of translational neuro-sciences and neurotherapeutics at the John Wayne Cancer Institute and Pacific Neuroscience Institute in Santa Monica, CA, who treats some of the most aggressive brain tumors, had few options to offer his patients. Today, thanks to advances in genetic sequencing, he has been able to identify genetic mutations in the tumors of one third to one half of his patients. As sequencing becomes more sophisticated it provides a host of new targets for drug therapies.

A particular mutation may make a tumor more vulnerable to a specific drug. For example, the MGMT gene produces a protein that helps cells repair themselves. It also protects cancer cells from the lethal effects of some chemotherapy, allowing them to proliferate, resulting in tumor growth. In patients with glioblastoma multiforme (GBM), an aggressive brain tumor, a mutation in MGMT can be beneficial because the MGMT repair protein doesn’t work as well. In these patients, the chemotherapy drug temozolomide can be more effective because the mutation means the cancer cells cannot repair themselves, and they die.

Dr. Kesari thinks in five to 10 years this level of precise testing, imaging, and treatment in oncology will become routine in many other fields of medicine.

The development of exome sequencing—a partial sequencing of a person’s DNA—has allowed doctors to identify genes responsible for specific diseases. For example, cerebellar ataxia, a condition that affects coordination and balance, could be caused by any of more than 600 different genes. Before exome sequencing, finding the exact gene was like looking for a needle in a haystack, says Brent L. Fogel, MD, PhD, FAAN, associate professor of neurology and human genetics at UCLA who researches, diagnoses, and treats genetic forms of ataxia.

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