NIH Names PD Research Targets

Just two years after the release of its groundbreaking agenda for Parkinson’s disease research, the government’s leading medical research agency has released a report card on where we are today in the quest for the cause and cure of this debilitating neurologic disorder … and how we should be allocating resources to the next phase of the struggle.

The report by the National Institutes of Health (NIH), prepared at the request of Congress, cited six research areas in particular as priorities. One of these is the field, known as “translational research,” that links basic and clinical studies — sometimes referred to as the bridging of the space between “bench and bedside.” The second is the study of the non-motor aspects of Parkinson’s, such as the mood disorders and digestive complications that affect so many people who live with the condition.

One item on the list — the development of so-called “bio-markers” that would enable doctors to track how fast and far Parkinson’s has developed in a patient — is already the subject of an invitation to submit proposals issued by the Michael J. Fox Foundation for Parkinson’s Research. The Board of Directors of the Parkinson’s Disease Foundation has just voted $250,000 towards this project.

Another promising research opportunity on the list involves further studies of gene therapy. The report recommends engaging in gene-therapy research first in animals. Only when the procedure has been shown to be safe would research be extended to human beings.

A fifth research priority is the identification of new animal models for Parkinson’s studies. The final one is learning more about how Parkinson’s affects the systems of the brain that produce dopamine — the chemical “messenger” that is deficient in people who have Parkinson’s.

January Consortium Paved the Way
Much of the material for the NIH report came from comments and suggestions made at a consortium of scientists and leading laypersons, convened by NIH on January 7–8, 2002.

The consortium opened with a report on progress to date from Dr. Diane Murphy, Director of the Parkinson’s program at the National Institute of Neurological Disorders and Stroke (NINDS). Included in Dr. Murphy’s report were financial estimates showing that during the year ending on September 30 (FY 2002), some $200 million will have been spent on Parkinson’s research by the NIH as a whole — almost one-third more than NIH spent two years ago.

Parkinson’s advocates praise the increase, but note that it still falls short of the budget that was prepared by the NIH scientists who drew up the original Agenda in the spring of 2000. This budget, known as a “professional judgment estimate” (PJE), called for additional expenditures of some $300 million by the end of 2002 —$100 million more than NIH says will be spent as of that date.

NIH officials in turn respond with the argument that the PJE is just that — an estimate, not a budget mandate.

PD Research Targets

One section of the new NIH report on the Parkinson’s Research Agenda lists some of the significant recent scientific discoveries at Parkinson’s research centers.

These include:

The role that genetic mutations can play in PD: “This finding,” says the report, “linked the protein alpha-synuclein with familiar forms of Parkinson’s, and literally paved the way for the tremendous progress that has been made in understanding the role of genes in this disorder.”

The relationship between normal and abnormal declines in the motor system: “Understanding the differences (and relationship) between normal aging of the motor system and PD will be important to the development of new therapeutic approaches.”

Increased risk of PD from occupational exposure to heavy metals: Recent research indicates that certain heavy metals may directly accelerate alpha-synuclein fibrillation, a process that can lead to the development of Parkinson’s.

The value of stem cell research: “Numerous recent findings … have strongly suggested that some types of animal stem cells may be useful in replacing damaged neurons in a wide variety of neurological disorders, including PD.”

More widespread effect of PD on the nervous system than was previously thought: The finding may help researchers to diagnose and treat such problems as the drop in blood pressure that often accompanies PD.

Increased linkage between environmental agents and PD: A model produced by the laboratory administration of a pesticide to rats produces a form of parkinsonism. Other significant data have been gained from exposures both to single agents and to combinations. These data may more accurately simulate “real-world” applications.

Effects of dopamine and L-dopa on the protofibrillar form of alpha-synuclein: “This finding may not only help researchers design more effective treatments for PD, but also help them to understand why long term dopamine therapy can cause severe side effects.”

The report also outlines how the work of scientists in basic research that is not specifically related to Parkinson’s can nonetheless yield valuable insights into the workings of PD. Specifically cited were the discoveries on the workings of the nervous system by Dr. Paul Greengard, Dr. Eric Kandel and Dr. Arvid Carlsson, awarded the 2000 Nobel Prize in Physiology or Medicine. The three scientists have been honorees at the last two PDF spring galas, Dr. Kandel in 2001 and Drs. Greengard and Carlsson in 2002.