ALS Research Is ‘Like an Iceberg’

by Heather Durham, Ph.D. on Wed, 2013-05-08 05:00

Heather Durham, Ph.D.

The pace of discovery in ALS research has increased exponentially, through expanding the scientific community and taking advantage of new technologies and methodologies. Examples are the new genes linked to ALS that have been identified over the last few years, and advances in imaging [a noninvasive way to view and track disease progression].

ALS doesn't develop the same in everyone and different mechanisms come into play at different stages of the disease. The more we learn about the differences and similarities in how the disease can manifest at the cellular level, the better positioned we are to develop effective therapies and to identify subgroups of individuals who will benefit from each approach.

Our lab addresses these issues using tissue culture and transgenic animal models to compare how mutant proteins that cause ALS disrupt the function of motor neurons.

By expressing ALS genes in cultured mouse motor neurons, we can assess toxicity in the context of the factors that make these cells particularly vulnerable to damage. Mutations in most of the ALS-linked proteins twist their shape so they tend to stick together and with other cellular constituents. This has many downstream consequences, including calcium dysregulation and general interference with gene transcription and RNA processing, depending on the class of mutant protein.

Our lab has been exploring the therapeutic potential of inducing expression of a class of proteins that “chaperone” and promote disposal of damaged proteins before they wreak havoc.

From the perspective of people with ALS and their loved ones, progress toward effective treatment may seem slow, but ALS research is like an iceberg — there is a huge foundation hidden under the water. As researchers, we have been building that foundation, and we are optimistic that we will soon break the surface.

About the Author

Heather Durham, Ph.D., is a professor in the Department of Neurology/Neurosurgery at the Montreal Neurological Institute of McGill University in Montreal, Quebec, Canada. She is also an MDA research grantee, and a member of MDA’s Medical Advisory Committee.

Her work seeks to understand the mechanisms responsible for motor neuron diseases and to identify therapies to assist vulnerable cells in defending themselves. Durham's research is linking the vulnerability of motor neurons to the way in which they respond to stress and deal with damaged proteins, and is seeking drugs that can boost levels of protective proteins or facilitate clearance of damaged proteins for stress relief at the cellular level. (View a 2010 video of Heather Durham speaking about ALS research.)

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