Personalized Medicine

I attended the International Parkinson and Movement Disorder Society meeting this past week and learned so much. One interesting topic was how "Personalized Medicine" should be part of our treatment approach.

"Personalized medicine" became a popular term for individualized treatments in the early 2000s as a result of the discovery of several medicines that targeted genetic causes of specific cancers.

In most medical specialties, the idea of personalized medicine has expanded beyond treatments targeting specific genetic causes of disease to include those targeting different clinical presentations of disease, which are labeled "phenotypes" in medical parlance.

The phenotype of a disease is the description of how it appears. A person with PD who mostly suffers from rigidity has a different phenotype than someone primarily with a tremor. A dictionary definition could be the appearance and/or behavior of an individual with a particular disease. One of the great mysteries is why diseases typically have so many phenotypes. A phenotype only rarely can be matched to a specific genotype (which means a genetic cause). We should all recognize that Parkinson's - similar to many other diseases - presents with a wide range of phenotypes.

The differences in phenotypes are discussed as a reason why each person with PD should be treated via personalized medicine. And I agree - personalized medicine is a treatment strategy used for generations. Doctors traditionally align therapies with the manifestations of a disease, in the context of their understanding of that disease. As scientific knowledge advances, so too does the understanding of diseases and therefore the range of treatment options that can be personalized for each patient. Advances in knowledge allow for new treatments, so our personalized medical care gets better.

Perhaps this makes more sense if we discuss in the context of a particular disease. Let's consider how treatment of lung cancer has evolved over recent decades.

Up until the early 2000s, we understood that lung cancer developed from different types of cells, so based on how the cancer cells appeared, we'd classify the lung cancer and treat with specific drugs, though unfortunately this chemotherapy did not work very well. But it was personalized based on our understanding of cancer.

More recently, we learned that some lung cancers develop when a gene turns on and causes production of an excess of a particular protein - exemplified by one called PD-L1. In response to this discovery, several drugs were developed to block the effects of PD-L1 (called checkpoint inhibitors) that are remarkably effective. These checkpoint inhibitors are only prescribed to people whose cancer makes excess PD-L1, so this is great example of personalized medicine.

When I was in practice, patients would often ask me whether personalized medicine was potentially an alternative to taking all the medicines I prescribed. I explained that these medicines were selected based on the way they experienced their disease - their phenotype - so they were receiving personalized medicine already.

It seemed to be a disappointing answer - as if they wanted me to tell them how these particular medicines were perfect for their individual genetic makeup or based on some other highly technical process. Sometimes the labels can get in the way of understanding that the goals are to improve a person's function, reverse their disease and reduce their risk of death - whether or not the genetic contribution to the illness are known.

Personalized medicine was what we were trying to do back when we selected treatments based on the appearance of the cancer cells just as it is now when we look for genetic markers akin to PD-L1. And it is what we do when treating any disease - match the treatment to the process we believe is causing the disease.

Our problem treating Parkinson's is that our treatments are closer to old fashioned lung cancer chemotherapy than they are to the use of checkpoint inhibitors. They make sense based on the accepted understanding of Parkinson's, but they are certainly not addressing the root cause of the disease. If they did, function would be restored and the disease reversed.

Could it be that drugs targeting alpha-synuclein will be proven effective? If so, this will change how we deliver personalized medical care. I will discuss in a future post why I have difficulty accepting the "synucleinopathy model" of disease. Let's hope I am wrong in this outlook, as there are drugs entering late stage clinical trials that could prove to be a way to conquer the disease within a couple of years. And hopefully there are others finding ways to treat the disease completely differently - as I am at Right Brain Bio - so that we can bring the equivalent of checkpoint inhibitors for lung cancer to people with Parkinson's. That will be a great moment - and I believe we are close.

So let's not worry about whether we should bring personalized medicine to Parkinson's. It is already here. Instead, let's focus on how to bring effective medicines to Parkinson's that can be plugged in to personalized medicine programs - medicines that restore function and reverse the disease.