ALS image
Progress on ALS

On 8 August 2003, Science published new research that marks one step toward a potential therapy for amyotrophic lateral sclerosis (ALS), the devastating neuromuscular condition also known as Lou Gehrig's disease. Because of widespread public interest in this disease and its treatment, we are making the full text of this interesting study available free of charge to all visitors to Science Online.

About the research. ALS wreaks its havoc through the degeneration of motor neurons, which in turn causes limb and respiratory muscles to atrophy. To explore possible therapies for ALS, B. Kaspar and colleagues, the authors of the new Science report, did not study the human disease directly, but used a mouse model of ALS -- specifically, mice with mutations in the gene SOD1, which encodes the antioxidant enzyme superoxide dismutase. SOD1 mutations are known to underlie a small percentage of ALS cases in humans, and SOD1-mutant mice show symptoms strikingly similar to those of human ALS patients.

Building on previous work, Kaspar et al. found that, by injecting a viral vector carrying a neurotrophic factor, insulin growth factor 1 (IGF-1), directly into the limb muscles of SOD1-mutant mice, disease progression in the mice was delayed, and the mice survived significantly longer than untreated mice -- even when the therapy was delivered after the mice had started showing overt ALS-like symptoms. The key to the treatment's effectiveness was the delivery method: the viral vector is capable of "retrograde transport" up the entire length of a nerve cell from the muscle to the nucleus of the motor neurons in the spinal cord. This allows the virus to deliver the growth factor directly to the ALS-affected neuronal cell bodies, and bypass the "blood-brain barrier" that makes conventional delivery of drugs to the central nervous system difficult.

Clearly, the new mouse study is a long way from offering a cure for human ALS; human clinical trials are only now being designed, and results from those trials are likely years away. Nonetheless, the research reported in Science could spur another look at the therapeutic potential of IGF-1, an option that seemed to lack promise in earlier trials.

[top of page]

New ALS Research
Retrograde Viral Delivery of IGF-1 Prolongs Survival in a Mouse ALS Model
B. J. Kaspar, J. Lladó, N. Sherkat, J. D. Rothstein, F. H. Gage
Science301, 839-843 (8 August 2003)
[Abstract][Full text][PDF]
Free to All Visitors

A growth factor slows the progression of a disease similar to amyotrophic lateral sclerosis in mutant mice, even when administered after symptoms appear.

Selected Web Resources on ALS
Following is a brief selection of Web sites that are useful for understanding ALS, and that help put recent research on the disease into a larger context.
About ALS
Rich set of pages providing basic information on ALS, its symptoms, and its possible causes. Site is a project of the Robert Packard Center for ALS Research at Johns Hopkins University.

Project A.L.S.
Organization involved in providing funding and support of ALS research (including the Kaspar et al. study), as well as information resources.

MedlinePlus ALS Information Page
Useful site includes ALS news, an interactive tutorial, information on research and clinical trials, and much more.

ALS Association
ALS advocacy group site offers news about research, a collection of links, and other resources.

International Alliance of ALS/MND Associations
Worldwide meta-association of groups that support people living with amyotrophic lateral sclerosis and motor neuron diseases.

Muscular Distrophy Association ALS Newsletter
Free monthly newsletter on ALS published by the Muscular Distrophy Association, which also maintains an information-rich Web site specifically on ALS.

Motor Neurone Disease Association
Web site of British organization includes interesting tutorial material, online publications, and more.
Link-rich portal targeted mainly at ALS patients, families, and caregivers.

ALS Survival Guide
Wide-ranging site includes information on causes of ALS, statistics on the disease, drug therapies, links, and a substantial array of other features.

Other Science Papers on ALS
Collected below are links to a number of earlier Science papers dealing with amyotrophic lateral sclerosis, its causes, and its possible treatments. As with all original research published on, access to the research papers below is free to registered users for papers published more than 12 months ago; more recent research papers, as well as Review articles and Perspectives, are available free to AAAS members or via individual article purchase.
Mutations in Dynein Link Motor Neuron Degeneration to Defects in Retrograde Transport
Majid Hafezparast et al.
Science300, 808-812 (2 May 2003)
[Abstract][Full text][PDF]

Functional Role of Caspase-1 and Caspase-3 in an ALS Transgenic Mouse Model
Mingwei Li et al.
Science288, 335-339 (14 April 2000)
[Abstract][Full text][PDF]
Free with Registration

Perspective: Stay the Executioner's Hand
Mark E. Gurney, Alfredo G. Tomasselli, Robert L. Heinrikson
Science288, 283-284 (14 April 2000)
[Summary][Full text]

Induction of Nitric Oxide -- Dependent Apoptosis in Motor Neurons by Zinc-Deficient Superoxide Dismutase
Alvaro G. Estévez et al.
Science286, 2498-2500 (24 December 1999)
[Abstract][Full text][PDF]
Free with Registration

Review: Genetic Classification of Primary Neurodegenerative Disease
John Hardy, Katrina Gwinn-Hardy
Science282, 1075-1079 (6 November 1998)
[Abstract][Full text][PDF]

Review: Genetic Neurodegenerative Diseases: The Human Illness and Transgenic Models
Donald L. Price, Sangram S. Sisodia, David R. Borchelt
Science282, 1079-1083 (6 November 1998)
[Abstract][Full text][PDF]

Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1
Lucie I. Bruijn et al.
Science281, 1851-1854 (18 September 1998)
[Abstract][Full text][PDF]
Free with Registration

Review: A Structural Scaffolding of Intermediate Filaments in Health and Disease
Elaine Fuchs, Don W. Cleveland
Science279, 514-519 (23 January 1998)
[Abstract][Full text][PDF]

Review: Life and Death of Neurons in the Aging Brain
John H. Morrison, Patrick R. Hof
Science278, 412-419 (17 October 1997)
[Abstract][Full text][PDF]

Bcl-2: Prolonging Life in a Transgenic Mouse Model of Familial Amyotrophic Lateral Sclerosis
Vladimir Kostic, Vernice Jackson-Lewis, Fabienne de Bilbao, Michel Dubois-Dauphin, Serge Przedborski
Science277, 559-563 (25 July 1997)
[Abstract][Full text][PDF]
Free with Registration

Altered Reactivity of Superoxide Dismutase in Familial Amyotrophic Lateral Sclerosis
Martina Wiedau-Pazos et al.
Science271, 515-518 (26 January 1996)
Free with Registration


AAAS and Science will continue to keep you at the forefront of advances in all areas of scientific inquiry. Visit to join AAAS today, and read about the next important research insights in your own copy of Science.
This portal to new ALS research is sponsored by Ambion, Inc.

RNA from regions of the human brain