Two ALS Association-Initiated Grants Continue to Support Critical Resources for Clinicians and Scientists Globally

“The ALS Association is very pleased to continue support of these two critical resources that impact scientists and clinicians globally,” said ALS Association Chief Scientist Lucie Bruijn, Ph.D.  “These initiatives are helping to provide faster, more efficient research data acquisition and processing.”

The ALS Online Genetics Database (ALSoD)

The first grant is awarded to the team of Ammar Al-Chalabi, Ph.D., F.R.C.P., Dip.Stat., King’s College London, UK; John Powell, M.A., D.Phil., King’s College London, UK; and Peter Andersen, M.D., D.M. Sc., Umeå University Hospital, Sweden for their work to develop and host the ALSoD, which is freely available at http://alsod.iop.kcl.ac.uk).

This website provides a continuously-updated summary of all the knowledge about ALS genetics from across the globe in one place.  ALSoD has multiple tools to analyze genes that have been studied extensively, such as TARDBP and SOD1, as well as specific links that can be helpful in making predictions, such as the effect of mutations on protein structure and function.

The ALSoD website is designed to allow easy access to information about ALS-causing gene variants and their effects on clinical patterns of ALS.  When enough information has been collected, ALSoD automatically displays graphs and produces statistics that show any relationships between genes and types of ALS, and researchers can explore these associations themselves.

ALSoD is integrated with multiple databases, including PubMed, the UCSC and Ensembl Genome Browsers, OMIM, GeneMania and many other bioinformatics resources to provide a seamless experience.  For example, it is possible to identify the most up-to-date list of genes implicated in ALS, explore their interactions and pathways, and review the relevant literature without leaving the website.  The ALSoD database keeps up with the rapid advances in genetics by adding new gene findings as they occur, both from published reports and from unpublished genetic and clinical information direct from one of the twelve registered international research groups.

To stay at the cutting edge, the development of new online research tools is a high priority.  For example, while many different mutations have been said to cause ALS, the strength of evidence varies.  The investigators plan to generate a credibility score that will help researchers understand how strong the evidence is for any particular mutation.  In addition, mapping of where mutations are found, using Google Earth within ALSoD, allows users to view the geographical distribution of reported gene variations associated with ALS.

The investigators are also developing tools to store and analyze information from genome-wide association studies, Next Generation Sequencing and gene expression studies.  They will expand the data to include findings from frontotemporal dementia research because there is overlap with ALS in some cases.

Currently, ALSoD displays information on 73 ALS genes (17 for familial ALS), 298 mutations, and 419 people with ALS (343 with detailed clinical data).

TREAT ALS/NEALS Clinical Trial Network

The second grant will provide continued support to the North East ALS Clinical Trials Network led by Merit Cudkowicz, M.D., M.Sc., Professor of Neurology at Massachusetts General Hospital, at Harvard Medical School and Jeremy Shefner, M.D., Ph.D., Professor and Chair of Neurology, Upstate New York Hospital, at State University of New York.

The TREAT ALS/NEALS Clinical Trial Network was established to develop the infrastructure necessary to rapidly complete clinical trials of new therapeutic agents and to provide partial funding for individual trials.  The network is comprised of over 92 clinical locations throughout U.S. and Canada.  Founded in 1996, NEALS has developed rigorous standards for clinical trial performance, standards for training and validation for individual sites, and much of the infrastructure to perform trials.

Through The ALS Association funding, the network was able to enhance a comprehensive clinical trials management system for the ALS community, and several ALS Association-funded studies benefit from this infrastructure.  The system makes tracking important trial documents easier and facilitates the collection of fluid and tissues samples from clinical trials.  In addition, an ALS biorepository has been developed that is a resource available to all investigators to facilitate biomarker studies.

The Association funding has enabled the establishment of a protocol to develop new outcome measures used in clinical trials and to train staff at NEALS sites to perform these measures and to track reliability between centers.  Additionally, new and existing investigators have benefited from training to conduct high quality clinical studies.

The network has supported a total of seventeen clinical research projects in ALS, including three completed clinical trials, ten active clinical studies, and four developing studies.  The network enabled the rapid completion of a phase II trial of Dexpramipexole and the compelling results of the well designed study contributed to the initiation of a phase III trial and the partnership between Biogen-Idec and Knopp Biosciences.

With a stable ALS clinical trial infrastructure now in place, the investigators propose to expand the ability of the TREAT ALS/ NEALS Network to perform ALS clinical trials by addressing obstacles still facing ALS clinical research, such as trial enrollment, staff training and a general lack of funding for critical clinical trial management components.  The investigators plan to continue to support the performance of ALS clinical trials through the use of their infrastructure and trained personnel.  Specifically, they will provide support systems for under-funded ALS clinical research projects; increase the ability of site staff to perform efficient, high-quality ALS trials; and improve patient education and enrollment in ALS clinical research.  For more information about clinical trials and the network, see the spring 2011 issue of “Research ALS Today” http://www.alsa.org/research/today/.