Beate Ritz, MD, Ph.D. is a Professor of Epidemiology and Environmental Health

Sciences and Neurology at UCLA. Her team investigates environmental and genetic

factors that influence the risk of developing chronic brain disorders. Parkinson’s disease

and the measurement of environmental factors has been a special focus of her lab for

more than two decades. She is the principle investigator of two of the largest and on-

going community-based studies of Parkinson’s disease worldwide located in the central

valley of California and in Denmark. These studies allowed her team to identify

environmental and genetic risk factors for Parkinson’s disease onset and progression.

They also showed how our genetic make-up makes some of us vulnerable to

neurodegeneration when exposed to environmental toxicants. She is the current

President of the International Society of Environmental Epidemiology and has served on

numerous National Academy of Sciences committees.

The following has been paraphrased from an interview with Prof. Beate Ritz on February 2, 2018.

(Click here for the full audio version)

Over the course of your career, what changes have you seen in the attention paid by the field to studying the effects of the environment on neurodegenerative disease?

There has always been a tug-of-war between the environment and genetics when it comes to identifying the causes of neurodegenerative diseases. For a while Parkinson’s was thought to be caused by environmental factors because the MPTP toxin was discovered in the mid 80’s by Dr. Bill Langston to instantaneously cause PD. Everyone then jumped on toxins thinking that if we found this one toxin that caused PD there must be a lot more out there that we just haven’t discovered yet. Then, in 1997 the alpha-synuclein gene was discovered to also be capable of directly causing PD. This coincided with the explosion of the field of genetics and it shifted everyone’s interest, suddenly everyone was focused on this protein that was believed to cause PD even though we still don’t really know what the protein does. Then the GWAS era (genome-wide association studies) arrived, where a number of genetic variants were identified as risk factors. These taught us a little bit, but we still don’t actually know that much more about Parkinson’s and what causes it in most people.

So, studies into genes and the environment ride these waves of discovery. Now, people are starting to examine the links between genetics and the environment, which has been the focus of my research since the early 2000’s.

Most people think of environmental exposure as just air pollution and pesticides in our food, what are some of the other major sources of environmental toxins that we should be considering?

As a public health researcher I should point out that we often really don’t know what’s in the air we breathe or the water we drink or the food we eat, and all of that can contribute to chronic exposures to toxicants and add up over a lifetime. Pesticides are particularly troublesome, they include a very wide swath of chemicals, in California for example there are 650 different chemicals that are major agents in pesticides. Some also change quickly because pests become resistant to certain types of pesticides, so the industry is constantly trying to come up with new products. We know even less about the new ones that come out and what they do, it’s really a shifting target. We need to take this much more seriously because of the widespread use of these chemicals and because they often contaminate our air, water and food.

Do you think there is a significant difference between the factors that lead to the onset of neurodegenerative diseases and the factors that contribute to further decline after onset?

We don’t have a good handle on this because we mostly focus on the risk factors that lead to the disease. We haven’t really started to look seriously at those factors that lead to faster or slower decline, which is what patients care most about. It’s really difficult to follow patients over long periods of time, but what we see in the studies that we have done suggests that the same factors that lead to the disease are also candidates that influence progression.

How far away are we from being able to accurately test for environmental factors that lead to neurodegeneration in an individual?

I’ve been hoping that we could find markers of long-term environmental exposure. I collaborate with geneticists and basic scientists looking for some of these markers, but we are just in the infancy of developing these methods. I’m hopeful that we will be able to develop markers that give us a read out of long-term environmental exposure but we aren’t really close to getting there yet.

Could you talk about the project you are a part of in California to implement a Parkinson’s disease registry and what you hope will come from it?

For chronic diseases, what you really need to do is study them on a population basis because we usually get them at an older age, but we know that everything you do over your life time plays a role in getting the disease. So to really study what that is we need a census of patients, which is what this registry is. What we have now are just the patients seen in clinical settings and these patients and their exposures do not accurately represent what we see in the community. This registry would be the most efficient way of getting an idea of how diverse Parkinson’s disease is and how widespread exposures are that are relevant to the disease in our communities.

If you were to try and map the environmental and genetic factors that make one more susceptible to neurodegenerative diseases, how complex do you suspect that map would be and what, if any, clinical relevance do you think it might have?

I think it would be a very complex map, however, any complex map has important focal points that we could target. There could be 1, 2 or 10 really important points that we could focus on and that could allow us to make a substantial difference in people’s lives. That’s really the art of doing this kind of research, developing an understanding of the most important factors from the long list of complex interactions between various environmental and genetic factors. It’s something I have been working on for the last 20 years, taking what we learn from basic sciences and genetics and adding this to what we know about major environmental factors to figure out what makes someone more susceptible to getting a disease. The hope is that in the end we could examine people at the prodromal stage (when patients exhibit the earliest warning signs of a disease) and be able to say something like, your head injury, exposure to a certain pesticide, and your inactive lifestyle, plus this certain genetic trait have all added up to make you more susceptible to developing the disease and you should take extra precautions to ensure you don’t get it.

When we look back 20 years from now on research into neurodegenerative diseases going on today, what do you believe will reveal themselves to be the biggest mistakes we are currently making?

The problem is that these diseases start much earlier in life, usually there is a 10 to 20 year lag between the start of the disease and symptoms allow us to diagnose it. Those are the years in which we could possibly intervene and make a difference in the progression of the disease. But we don’t know currently when this starts to happen and we don’t really have any way of intervening yet as we don’t have anything that is really neuro-protective.

In the early 2000’s there was more of a push for multi-disciplinary approaches to studying neurodegenerative diseases that required clinicians to work with basic scientists as well as epidemiologists to solve these questions together. That was an extremely stimulating and very inspiring period. Unfortunately this approach has gone by the wayside because there has been no call to action and no incentives to form these multi-disciplinary groups. There are still researchers from different fields talking to each other, but unless we encourage our younger colleagues to engage in this same dialogue I don’t think we are going to make as much progress as we could.

Click here for a another very informative talk from Prof. Ritz