This week, I have my dear friend and brilliant scientist, Dr Johnathan Ng, PhD in Biomedical Engineering at Columbia University, give us a crash course on personalized medicine – what is it? what does it mean for the field of medicine and society? Johnathan now works at a start up in NYC, which grows bone for facial reconstruction. This is a two-part series, with the first part focusing on an overview of personalized medicine, and the the second part focusing on implications for healthcare systems and Governments. A super educational read for anyone with interest in the healthcare space. I certainly learned a lot while editing. Enjoy!

It’s getting personal

Personalized medicine has been hailed as the future of healthcare. At the forefront of clinical and scientific debate lie questions that could transform our healthcare landscape. Can medicine truly be personalized? Will the “personalized medicine” of today simply be medicine in the future? How can we leverage the personalization of medicine for the betterment of humanity?

A Brief History of Personalized Medicine

First, what is personalized medicine? In contrast to conventional medicine, which applies statistical information taken of the general population to the individual, personalized medicine uses information about a person’s genes, proteins and environment to prevent, diagnose and treat diseases.

As the prescient Hippocrates once said, “It’s far more important to know what person the disease has than what disease the person has.” The roots of personalized medicine predate our understanding of the human genome. For example, blood type matching for transfusion between the donor and the recipient to prevent hemolysis due to incompatibility was first reported more than century ago.

However, it is only with recent advances in genome sequencing technology that we can map the human genome and study it at an unprecedented scale. This has ushered in a new era of personalized medicine. In this overview, I cover three aspects of personalized medicine: 1. Personalized disease modifying drugs; 2. Autologous cell therapies; and 3. Stem cell therapies.

1. Personalized Disease-Modifying Drugs

Some of the earliest breakthroughs in personalized medicine came in the form of personalized disease-modifying drugs, including:

1. Breast cancer. In 1998, researchers found that a particular type of protein, HER2, was overexpressed in aggressive breast cancer cases. Consequently, Herceptin, an antibody therapy which suppresses HER2 activity, and a companion diagnostic test for HER2 expression in breast cancer cells were approved. These have become standard treatments today.
2. Cystic Fibrosis. In 2012, the U.S. Food and Drug Administration (FDA) approved Kalydeco, a drug for treating cystic fibrosis by restoring the function of a protein misfolded due to mutation of the G551D gene. Restoring this protein’s function abolishes mucus buildup that leads to life-threatening respiratory and digestive problems. With that approval, Kalydeco also became the first drug that treats the underlying cause of the disease and not the symptoms.
3. Immunotherapy. Over the last two years, a new class of antibody called checkpoint inhibitors was approved for treating some cancers. Opdivo and Keytruda are antibodies that disable checkpoints in immune cells by neutralizing the programmed death receptor (PD-1). Thus, immune cells bypassing these checkpoints are able to kill cancer cells more effectively. In a recent pivotal study, Merck showed that Keytruda reduced the risk of death by 40% among patients expressing PD-L1 levels greater than 50%.

2. Giving our cells superpowers: Autologous Cell Therapies

Besides harnessing information encoded in our genes to improve treatment response, personalized medicine is also about helping to unleash the immense capacity of our body to repair and mend itself.

Our cells contain information, latent or potent, that can be manifested into cure. Autologous cell therapy involves harvesting cells from a patient’s body, enriching the cell population outside of the body, and re-infusing the cells into the body.

The New York Times documented the miraculous journey of Celine Ryan who enrolled in a revolutionary clinical trial for her advanced colon cancer. Inherent in our immune system is the ability of lymphocytes[1] to locate, infiltrate and kill tumors. However, some tumors grow to counteract our immune response by damping or evading it. To help Ms Ryan overcome her tumors, the doctors mined her lymphocytes from the tumors, enriched and re-infused them into her body. These enriched lymphocytes intensified their attack on the tumors and after 9 months, she gradually recovered and entered full remission.

The success of Ms Ryan’s clinical trial provided scientists with a new strategy: engineering and enhancing patients’ T-cells to target and destroy tumor cells with distinct markers. These engineered cells are known as chimeric antigen receptor (CAR) T-cells, and they have both the ability to locate and destroy their targets. Emma Whitehead, 6, suffered from acute lymphoblastic leukemia (ALL) and twice relapsed from chemotherapy treatment. Without any other resort, her parents turned to an experimental treatment which used CAR T-cells to target CD-19, a marker expressed by both her healthy and malignant B-cells. The doctors rescued Emma from the brink of death and she is now cancer free.

3. Stem Cell Therapies

Stem cells are unspecialized cells with the ability to renew and differentiate into specialized cell types that make up our entire body during development. Even in adulthood, stem cells exist in multiple places in the body such as the bone marrow and fat tissues. Not surprisingly, they have also been heralded as a frontier for personalized medicine. At the biotechnology startup where I work, we engineer bone from a patient’s fat-derived stem cells to replace bone where it is needed. We successfully engineered bone from fat-derived stem cells and used it to regenerate a pig’s missing facial bone. Our next goal is to get the product into the clinic to help patients suffering from bone defect. There is reason to be optimistic: skin, trachea and bladder engineered from patients’ cells have already been successfully implanted.

Some key limitations remain in stem cell therapy as adult stem cells have a limited range of differentiation. Although embryonic stem cells are pluripotent (meaning that they can differentiate into any cell type), there are ethical limitations to using them as they require the sacrifice of embryos.

To overcome these limitations, Dr. Shinya Yamanaka and colleagues discovered a method to induce adult somatic cells into a pluripotent state. These cells, termed induced pluripotent stem cells (iPSCs), have ignited the imagination of scientists and clinicians as they could enable the treatment of diseases caused by the failure of specialized cells such Parkinson’s disease and heart failure. In a recent interview, Dr. Yamanaka (now a Nobel laureate) confirmed that clinical trials for iPSCs therapy will be underway over the next decade. However, he also cautioned against overstating the benefits of targeted stem cell therapies as they can only address a small subset of all human diseases.

What does personalized medicine mean for society?

Personalized medicine is improving the precision and efficacy of treatments by enabling the clinicians to make more well-informed decisions. Advances in pharmacogenomics have helped to reduce wastage of drugs and their incurred cost due to non-responders, and tailor the dosage according to the patient’s metabolism.

However, these efforts are not without cost. The cost of developing targeted therapies in an era of precision medicine is almost $2.6 billion. These treatments also bring about new regulatory risks for hospitals and Governments, who are facing increasing pressure to green light advances that give people unprecedented (but perhaps unproven) hope. My next article elaborates on three areas that Governments and healthcare systems need to pay attention to when it comes to personalized medicine, to maximise its benefit to public good.

Stay tuned!

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[1] Tumour-infiltrating Lymphocytes