The summer of 2014 was all about people pouring orange buckets of ice water over their heads and challenging others to do the same. But as fun as it was, the individuals were not just goofing off. They were rising to the Ice Bucket Challenge that encouraged people to either douse themselves with the ice water or donate $100 USD towards ALS research. The dare that went viral globally enabled the Foundation to raise an astounding $115 million USD in a few short months. Now, just a year later, the generous donation is helping facilitate new breakthroughs in the disease that currently has no cure.
Also known as Lou Gehrig's disease, ALS (amyotrophic lateral sclerosis), is a progressive neurodegenerative disorder that affects nerve cells in the brain and the spinal cord. Despite years of research, scientists have been unable to find what causes the disease. The last breakthrough came about a decade ago when researchers discovered that 97% of ALS patients had clumps of a protein called TDP-43 outside the nuclei of their brain cells.
What they were unable to determine was the precise role of TDP-43 or the consequences of the clumping. Some thought that the clusters themselves were toxic and responsible for causing the disease. Others believed that they were making the TDP-43 protein "sticky" and preventing it from doing its regular job.
A team of researchers led by graduate student Jonathan Ling and Professor Philip C. Wong, from Johns Hopkins Medical, in Baltimore, Maryland, recently decided to investigate if there was any truth to either theory. They began by deleting the TDP-43 cells from lab-grown mouse and human cells. What they found was this enabled unwanted genetic materials called cryptic exons that are typically blocked by the TDP-43 protein to interact with the nerve cells. As a result, both the mouse and human cells died within a few days.
To confirm that it was the unwanted cryptic exons that were responsible for killing the cells, the scientists injected them with a protein that mimicked the properly functioning TDP-43. Sure enough, the cells came back to life and returned to their original state.
The researchers who published their findings in the journal, Science, on August 7th, also studied brain autopsies of patients with ALS. As they had suspected, in addition to the buildups of TDP-43, the degenerated brain cells also contained cryptic exons. A similar study performed on healthy brain cells found no evidence of either.
While the breakthrough is encouraging, more tests are necessary to determine if the mimicking protein is as effective on not just the mice cells, but the organism as a whole. If the results prove favorable, the researchers hope to start human clinical trials within a few years.
Wong says that though the team has been researching ALS for many years, this development can mainly be attributed to the extra funding they received from the successful ALS Ice Bucket Challenge. The scientist says that knowing that funding for this and all future trials were assured encouraged the team to take on riskier experiments.
Though that is certainly good news, critics argue that the vast amounts of money allocated to ALS research that affects less than 15,000 people annually, is taking away from resources to other causes that affect more people. Wong, however, believes that their new understanding of TDP-43 will have a much wider impact. He thinks it could be the key to finding cures for other neuromuscular diseases such as Alzheimer's, muscular dystrophy, and inclusion body myositis (IBM).
In fact, the researcher is such a believer in the cause that he and Ling restarted the Ice Bucket Challenge by dousing themselves with two large orange buckets of freezing water. They have also dared six others, including billionaire Bill Gates and astrophysicist Neil deGrasse Tyson, to do the same!