A study of amyotrophic lateral sclerosis recently published in The Proceedings of the National Academy of Sciences USA shows a complex genetic interplay between motor neurons and astrocytes. Led by scientists at Columbia University and supported by labs at the HudsonAlpha Institute, the study provided novel insights into the pathways leading to motor neuron-specific degeneration.
According to HudsonAlpha President and Director Rick Myers, Ph.D., “This research illustrated the linkage between motor neurons and neighboring nonneuronal cells, called glia, in ALS progression.” Astrocytes are one of three types of glial cells.
Genomic sequencing and bioinformatics analyses conducted at HudsonAlpha identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration. Motor neurons are the cells that die during the disease, leading to paralysis. Astrocytes normally support motor neurons but during disease progression contribute to motor neuron death.
Myers, who worked closely with Drs. Hemali Phatnani and Tom Maniatis at Columbia University Medical Center, said the study took an integrated approach to analyzing ALS disease mechanisms by combining ALS patient autopsy samples, mice that contained the same mutation present in humans with ALS and cell culture analyses.
With mutated glia, it was shown that specific gene-expression and signaling pathways are altered in a way that may contribute to ALS’ signature degeneration. “One such pathway, which is called the TGF-β signaling pathway and plays a role responding to stress or injury and protecting against neuronal damage, was particularly disrupted by the ALS mutation,” Myers added.
This research, he said, illustrates the power of partnerships. “The collaboration was critical for achieving these scientific findings. We have to understand how the disease develops and progresses.”
ALS is a severe and complex neurodegenerative disorder that affects adults and is characterized by the progressive death of motor neurons and muscular atrophy due to loss of their innervation. The disease’s progression is highly individualistic, paralyzing patients and ultimately curtailing breathing. There is no cure or treatment today that halts or reverses its course. Approximately 30,000 Americans have the disease, with 5,600 new diagnoses occurring each year. Life expectancy averages two to five years from diagnosis. The cost of medical care, equipment and home health caregiving rises significantly as the disease progresses.
To date, several genes have been identified in which mutations result in the disease, but their detailed workings are not yet clear. Discovering the genetic causes of ALS will point to potential targets for new drug development and better disease management.
The project was funded by grants from the National Institutes of Health; other funding organizations include but are not limited to the ALS Therapy Alliance, The Greater New York Chapter of the ALS Association, The Alabama Chapter of the ALS Association and HudsonAlpha Institute. This research is ongoing.
The abstract of the paper Intricate interplay between astrocytes and motor neurons in ALS may be found here.
Media Contact: Beth Pugh
About HudsonAlpha: HudsonAlpha Institute for Biotechnology is a nonprofit institute dedicated to innovating in the field of genomic technology and sciences across a spectrum of biological problems. Its mission is three-fold: sparking scientific discoveries that can impact human health and well-being; fostering biotech entrepreneurship; and encouraging the creation of a genomics-literate workforce and society. The HudsonAlpha biotechnology campus consists of 152 acres nestled within Cummings Research Park, the nation’s second largest research park. Designed to be a hothouse of biotech economic development, HudsonAlpha’s state-of-the-art facilities co-locate scientific researchers with entrepreneurs and educators. The relationships formed on the HudsonAlpha campus allow serendipity to yield results in medicine and agriculture. Since opening in 2008, HudsonAlpha, under the leadership of Dr. Richard M. Myers, a key collaborator on the Human Genome Project, has built a name for itself in genetics and genomics research and biotech education, and boasts 26 biotech companies on campus.