Space is often called the final frontier, but there is a terrain much closer to home that we have yet to conquer, and that is the human brain. This is in large part because it is impossible to use invasive techniques to examine the brain of a living person, which makes research into Parkinson’s disease (PD) vastly more difficult than it is for most other health conditions.
But there is good news. Scientists are making inroads in part because thousands of people with Parkinson’s — in some cases, along with their family members — have donated their brains to science.
Two places where advances are being made are the brain banks supported by the Parkinson’s Disease Foundation (PDF) at Columbia University Medical Center and Rush University Medical Center. According to Roy Alcalay, M.D., M.S., assistant professor of neurology at Columbia, “much of what we know about Parkinson’s and its causes has come from studying brain tissue.”
In a very real sense, donating one’s brain to science is “the gift that keeps on giving.” At Columbia, under the direction of Jean Paul Vonsattel, M.D., the brain bank uses innovative methods to ensure that donations benefit science not only at Columbia, but also at collaborating research centers around the world. In the past 22 months, the tissue donated by 767 generous individuals has provided thousands of samples to more than 150 research laboratories, one third of which are outside of Columbia. Similarly, Rush has become a leading repository of PD brain tissue, with its samples being utilized to advance research at 100 scientific labs around the world. Brain donations at both centers are allowing scientists to make strides in understanding the changes in the PD brain and how to treat them. Here are a few highlights:
- Lorraine Clark, Ph.D., and her colleagues at Columbia have used brain donations to identify a previously unknown mutation in the gene known as glucocerebrosidase that significantly increases the risk of developing PD. Their discovery has provided a new therapeutic target for drug development. It also prompted further research that subsequently revealed how mutations in the gene may lead to the accumulation of toxic structures called Lewy bodies — the cellular hallmark of Parkinson’s disease — inside brain cells.
- Another group at Columbia led by David Sulzer, Ph.D., has used donated brain tissue to demonstrate how Parkinson’s hinders brain cells from being able to dispose of and recycle damaged proteins properly, leading to the death of the cells in PD. This work has in turn shed light on the need for treatments that can help restart or speed up the cellular recycling process.
- Jeffrey Kordower, Ph.D., and colleagues at Rush have used donated brain tissue to clarify how dopamine-producing brain cells are lost in the early stages of PD — a discovery that is crucial to designing strategies for early detection and treatment. Understanding this process also may help to explain why some experimental treatments — for example, growth factors — are ineffective in later stages of PD.
- Scientists at Rush, including Dr. Kordower along with Christopher G. Goetz, M.D., and Cynthia Comella, M.D., helped to fine-tune plans for Parkinson’s clinical trials by examining the effects of investigational treatments in post-mortem brains. They showed, for example, that injecting an experimental treatment called GDNF into one location of the brain (the cavities) did not stop neurons from dying. Their work suggested that injections into other areas (regions with the dying neurons) may be more successful.
- More generally, scientists at both institutions are beginning to find links between the PD brains and PD symptoms. This is possible because brain donors at both centers leave a second gift to science — their medical records. This means that scientists are able not only to accurately diagnose PD, but also to compare changes in the brain tissue with the symptoms that people experience during their lifetimes.
Along with these highlights, there are countless other findings made possible by brain donation. Thousands of people with Parkinson’s have made this vital contribution not only to scientific progress, but also to future generations who will benefit from better therapies and ultimately, from the cure.