The ALS Association Funds New Biomarker Study Seeking Faster and More Accurate Diagnosis of ALS
Addendum - April 21, 2004
Biomarker Study Results Are Preliminary
While the promise of biomarkers is very exciting, recent articles in the media, which suggest that ALS markers have been found, are premature. The number of individuals involved in this early study is too small to confirm that the markers actually track the disease. In addition, it is important to use different techniques to verify that these markers are true ALS markers.
The desperate need for an early diagnosis can cause study results to be overstated. One thing is certain, it is vitally important to perform appropriate follow-up studies, such as research The ALS Association is funding, to validate study results.
Application of Cutting Edge Technologies May Lead to Earlier and More Effective Therapy
February 2, 2004
A new study to find a more rapid and accurate diagnostic test for amyotrophic lateral sclerosis (ALS) using "biomarkers" found in cerebrospinal fluid and blood is being funded by The ALS Association.
The study, Identification of Diagnostic Biomarkers and Therapeutic Targets for ALS, brings together researchers from academic institutions and biotechnology sectors in a collaborative project that utilizes two distinct, cutting-edge technologies.
Investigators from Massachusetts General Hospital, the University of Pittsburgh School of Medicine and Metabolon, Inc. in North Carolina will work together on the project, which is being funded for one year with the potential for renewal after presentation of the initial data to The ALS Association.
Currently, people are diagnosed with ALS primarily by a process of ruling out other diseases in a lengthy and expensive process that is often fraught with discomfort and uncertainty.
"There is an urgent need to find a faster and more reliable diagnostic process that will enable earlier treatment and improve chances that therapy will alter the course of ALS," said Dr. Lucie Bruijn, science director and vice president of The ALS Association.
The research also may yield new methods to determine the progress of the disease by comparing the amounts of biomarkers - small molecules associated with ALS - at early and late stages. This type of test may also make it possible to measure the effectiveness of different drug treatments in clinical trials.
In the new study, investigators will analyze blood and cerebrospinal fluid from a control group and from ALS patients by using two different technologies that have the potential to strengthen and validate the findings.
Researchers believe that biomarkers for ALS are more likely to be detected in the cerebrospinal fluid that is contained in the central nervous system and bathes motor neurons in the spinal cord and brain. This fluid is in direct contact with cells that are dying in the ALS disease progression.
However, easier diagnostic testing in patients could be achieved if the same markers are found in the blood.
An initial study in 2003 by Robert Bowser, Ph.D., of the University of Pittsburgh School of Medicine found several small proteins in the cerebrospinal fluid of ALS patients that are not present in the same fluid from control patients and were sensitive diagnostic markers for ALS.
"ALSA has created a unique scientific collaboration that will greatly increase the speed by which we identify diagnostic biomarkers for ALS and new insight into the mechanisms of the disease," Bowser said. "We are very excited about the opportunities provided by this new collaborative research project. By confirming and extending our earlier results, we should be able to identify true diagnostic biomarkers for ALS and new targets for drug therapy."
In the new study, the Ciphergen Protein Chip mass spectrometry proteomic system will be used to confirm these initial findings in a larger sample pool of cerebrospinal fluid and from blood taken from ALS patients and control patients. Samples obtained from Massachusetts General Hospital and the University of Pittsburgh will include a variety of other neurological disorders and Alzheimer's disease. The diversity of control samples is critical to ensure that markers identified are specific to ALS.
The same set of samples will be tested at Metabolon, where the company's metabolomics platform will search for signatures of ALS by accurately measuring the spectrum of biochemical changes and mapping these changes to metabolic pathways. Metabolon is a leader in the application of metabalomics, a powerful and new scientific approach for the discovery and development of drugs and the early diagnosis of disease states.
In pilot studies, Metabolon has already established metabolic profiles from the blood of ALS patients for comparison to profiles from control groups. Initial studies have identified markers that can be used to distinguish disease tissue from normal tissue. To extend these findings, Metabolon investigators will expand the study to the larger sample set and analyze the profiles in cerebrospinal fluid.
"We are delighted to be working with ALSA on this project, and we are committed to make a difference in the lives of ALS patients," said Rima Kaddurah-Daouk, Ph.D., co-founder of Metabolon, Inc. "Using our novel metabolomics approach, we will be evaluating global biochemical defects in ALS in ways not possible before. We will ultimately be able to draw a map that can highlight diagnostic markers for ALS and novel targets for drug design."
Dr. Bowser, of the University of Pittsburgh School of Medicine, Merit Cudkowicz, M.D., Massachusetts General Hospital, Robert H. Brown, Jr., Ph.D., M.D., Massachusetts General Hospital, and Rima Kaddurah-Daouk, Ph.D., Metabolon, Inc., are the principal researchers in the new study.
This unique study was initiated by The ALS Association as part of its Lou Gehrig Challenge: The Campaign to Cure ALS. The Lou Gehrig Challenge is the most ambitious and promising privately-funded research program ever undertaken aimed at finding effective treatments and, ultimately, a cure for ALS. Results of the first year study will be presented to the Lou Gehrig Challenge Scientific Advisory Committee for consideration of renewal.
To provide samples for this study, patients and physicians should contact Merit Cudkowicz at 617-726-0563, Kristyn Newhall at 617-726-9122 or Robert Bowser at 412-383-7819. Investigators are seeking to analyze samples from familial ALS, sporadic ALS, PLS and pure lower motor neuron disease.
