November 27, 2007

Conference Focuses on Speeding ALS Drug Discovery and Clinical Trials

In late September 2007, The ALS Association brought together 30 basic scientists, clinicians, and industry researchers for a three-day conference on “Drug Discovery, Biomarkers, and Clinical Trials in ALS.” The topic was inspired by The Association’s TREAT ALS (Translational Research Advancing Therapy for ALS) program, designed to accelerate the development of ALS treatments. The conference, held at the Banbury Center at the Cold Spring Harbor Laboratory in New York, was part of The Association’s workshop program, which brings together scientists from diverse areas to help spur research and define new directions in understanding ALS.

Increasing the rate at which new drugs can be tested with patients in the clinic depends on understanding the disease process, and discovering drugs that can affect that process. It also depends on structuring clinical trials so that they can be conducted with fewer patients over shorter times. Scientists at the conference examined each of these issues in depth. “Information sharing is one of the keys to speeding drug development,” according to Petra Kaufmann, MD, a participant and clinical researcher at Columbia University. Talk went on during the day-long meeting sessions, over coffee, all through dinner, and into the evening, as researchers examined every angle of the challenge.

A major goal of the Banbury conference was to forge links between the many groups that have an interest in finding treatments for ALS. The group included scientists from biotech companies and academic research laboratories, pharmaceutical industry consultants, leaders of non-profit disease research organizations, and physicians who conduct clinical trials.

“We hope that by bringing together these diverse groups of scientists, all of whom are dedicated to finding a cure for ALS, we will speed up the process of drug discovery and clinical testing,” said Lucie Bruijn, PhD, Science Director and Vice President for The ALS Association.

The major themes discussed during the meeting are:

Biomarkers of ALS progression are needed. A biomarker is a measurement, such as a blood test or imaging result, that tracks the disease process and the effects of treatment. Current trials usually measure decline in strength or ventilation, which may fluctuate even as ALS progresses. With a biomarker that changes more steadily, trials could be shorter or require fewer patients. Researchers weighed the advantages and practicality of several types of biomarkers, including counting the number of axon terminals remaining in a muscle (an axon is the long extension a nerve cell sends out from the spinal cord), novel neuroimaging techniques identifying brain degeneration and a high-tech analysis of metabolites in the spinal fluid. 

Drug discovery begins with the disease mechanism. A drug can have an effect on ALS if it interrupts some specific disease process, or corrects some specific deficit. To find such drugs, researchers need to understand the disease mechanism—exactly what goes wrong and why. This remains the biggest challenge in ALS, and scientists at the meeting discussed new studies investigating this question. Animal models remain the most important source of new insights into ALS, and the strengths and weaknesses of the animal models were hot topics for discussion.

Clinical trial design to address the numbers of patients required. The drug testing process is long and expensive. In a disease such as ALS, in which many possible drug candidates need to be tested to find an effective one, faster trials with fewer patients could speed up the process. Scientists discussed alternative trial designs and the challenges to meet this need.

For more information, see the following articles:

• ALS Researchers Exchange Information on Clinical Trials
• Drug Discovery in ALS: Animal Models are Problematic but Crucial 
• Speeding ALS Clinical Trials with New Trial Designs and Biomarkers