Tags Posts tagged with "Ride for Life"

Ride for Life

Ride For Life presents CSHL with $300,000 for ALS research: from left, CSHL Director of Annual Giving and Donor Relations Karen Orzel, CSHL Assistant Professor Molly Hammell, Ride for Life Founder Chris Pendergast, Stony Brook Associate Professor Josh Dubnau and Ride for Life board member Frank Verdone. Photo by Jessa Giordano, Cold Spring Harbor Laboratory

By Daniel Dunaief

The past can come back to haunt us, even in the world of genetics. Over the course of millions of years, plants and animals have battled against viruses, some of which inserted their genes into the host. Through those genetic struggles, explained Molly Hammell, an assistant professor at Cold Spring Harbor Laboratory, cells develop “elaborate ways to fight back,” even as they continue to make copies of these pieces of DNA.

Sometimes, when our defenses break down, these retrotransposons, or jumping genes, can become active again. Indeed, that appears to be the case in a fly model of amyotrophic lateral sclerosis, also known as ALS or Lou Gehrig’s disease.

Working on a fruit fly model of ALS, Joshua Dubnau, an associate professor at Stony Brook University, Lisa Krug, who earned her doctorate at Cold Spring Harbor Laboratory and is now working at Kallyope in New York, and Hammell showed that these ancient genetic invaders play an important role in the disease amid activation by a protein often linked to ALS called TDP-43.

A recent study, published in PLOS Genetics, “really proves that retroviral reactivation (as a consequence of TDP-activity) is … central to either causing or accelerating neuronal cell death when TDP-43 inclusions are present,” explained Hammell in an email. If TDP-43 plays the same role for humans, this would suggest that targeting this protein or the jumping genes, it activates could lead to potential treatment for ALS.

These collaborators showed that an aggregation of this protein turned on jumping genes. These genes can make copies of themselves and insert themselves in other parts of the genetic code. In this case, TDP-43 expression disrupts the normal immune-like system that silences retrotransposons such as gypsy, which is a particular type of jumping gene in the fruit fly.

When gypsy was activated, the fruit fly exhibited many of the features of ALS, including protein pathology, problems with movement, shortened life span and cell death or glia and neurons in the brain. The scientists were also able to turn gypsy off, which improved the health and extended the life span of the fly.

Mimicking this protein results in broad activation of several retrotransposons. If this also occurs in people, the disease may activate a retrotransposon that is the human analog to gypsy, called HERV-K, as well as other retrotransposons. The study also suggests that DNA damage caused by retrotransposons may active a cell suicide mechanism. Finally, this effort showed a means by which the protein disrupts the normal immune surveillance that keeps retrotransposons quiet.

To be sure, Dubnau cautioned that animal models of a disease may not translate when returning to people. Researchers need to look at more patients at all the retrotransposons in the human genome to monitor its prevalence, Dubnau suggested. If the link between retrotransposon activation and the development of ALS is as evident in humans as it is in the fruit fly, scientists may take an approach similar to that which they took to battle the human immuno-deficiency virus, or HIV. Retrotransposons have an RNA genome that needs to be copied to DNA. This, Dubnau explained, is the step in the process where researchers attacked the virus.

In a small subset of HIV patients who have motor neuron symptoms that are similar to ALS, Avi Nath, a senior investigator at the National Institutes of Health discovered that treating patients with the typical HIV medication cocktail helped relieve their ALS symptoms as well.

“What is not known is whether, for some reason, this subset of patients had an ALS syndrome caused by HIV or they were curing them” by treating HIV, Dubnau said. Nath is currently involved in one of two clinical trials to see if HIV medications help ALS patients. The next step for Dubnau and Hammell is to screen the tissue of numerous ALS patients after their death to see if their retrotransposons were elevated.

In addition to NIH funding, the scientists received financial support from Ride for Life, which is a not-for-profit organization started in 1997 that raises funds for research to find a cure for ALS, supports patients and their families through patient services and raises awareness of ALS. Every May, Ride for Life conducts a 12-day, 100-mile patient wheelchair ride across Long Island. Dubnau and Hammell, who received a $300,000 grant from Ride for Life in 2015, said they have been inspired by Ride for Life founder Chris Pendergast.

Meeting Pendergast “has had a big impact,” Dubnau said. “He’s a force of nature. He’s an incredibly strong and intelligent person.” Receiving funds from Ride for Life created a sense of personal obligation to Pendergast and many other people who “had raised that money through sweat and effort.”

Without funding from the Ride for Life Foundation, “We would not have the resources to obtain these samples and do the sequencing experiments necessary to prove that this is a clinically relevant phenomenon in a large number of ALS patients,” Hammell said.

Through an email, Pendergast explained that Ride for Life chose to fund the work by Dubnau and Hammell because the research met several criteria, including that it might lead to new strategies to treat ALS and the research was on Long Island, which is a “powerful affirmation for our generous donors.”

Pendergast emphasized the importance of funding basic ALS research. “We need to know why it develops, how it progresses [and] how it can be diagnosed and monitored,” he urged.

A resident of Huntington, Dubnau and his wife Nicole Maher, who works at the Nature Conservancy as a climate scientist, have a nine-year-old daughter, Caitlin. Reflecting both of her parents’ professional interests, Caitlin is going to a statewide science fair, where she is presenting her work on how temperature affects the life span of insects.

As for his research, Dubnau hopes a further exploration of TDP-43 might reveal an important step in the progression of ALS. He hopes this discovery may suggest a strategy researchers and clinicians can take that might “stop the cascade of events” in ALS.

Members of the Comsewogue High School girls varsity and junior varsity field hockey team dump water on themselves at the second annual ALS Ice Bucket Challenge on Wednesday Aug. 26. Photo by Giselle Barkley

As the president of the Port Jefferson Station Teachers Association, Beth Dimino is rarely hit in the face with whipped cream. But on Aug. 26, Dimino sat wearing a large black garbage bag as whipped cream from a pie toss dripped down her face and body — all in support of the second annual ALS Ice Bucket Challenge at Heritage Park in Mount Sinai.

Hundreds of people attended the event, which aimed to raise awareness of amyotrophic lateral sclerosis and money for research into the disease, through the Stony Brook-based organization Ride for Life. People who purchased a ticket could trade it for a chance to throw a whipped cream-filled plate at volunteers like Dimino.

Councilwoman Jane Bonner (C-Rocky Point) was one of many, including local school principals and teachers, to participate in the event’s dunk tank or pie-throwing games. For Bonner, supporting the cause is important, as her grandfather died from the rare disease around 35 years.

“It robs your body, not your mind,” Bonner said.

ALS affects nerve cells in the brain and spinal cord, causing motor neurons to degenerate. People with the disease lose control over their muscles, leaving them unable to speak, eat, move or breathe on their own. The cause of the disease is not yet known.

Bonner jumped at the chance to participate in the event this week.

“Chris just makes you want to [be involved],” she said about Christopher Pendergast, who founded Ride For Life in 1997 and has lived with the disease for more than 20 years. “He just inspired so many people to participate and bring awareness.”

According to Ray Manzoni, a member of the Ride For Life Board of Directors, Pendergast wanted to make this year’s event at Heritage Park bigger and better than last year’s ice bucket challenge, which focused on the ice bucket challenge itself.

Last year’s event occurred during the height of a worldwide trend in which people dumped buckets of ice water over their heads, and challenged others to follow suit, in order to bring publicity to the disease. Lori Baldassare, president of the Mount Sinai Heritage Trust, Bonner and Legislator Sarah Anker (D-Mount Sinai), all of whom attended this year’s event, were “instrumental in getting [the event] approved quickly” last year, according to Manzoni. That inaugural event was organized in four days.

Manzoni said this year they added the pie-tossing event, balloon twisting and face painting booths, cotton candy, hot dogs and more.

The Comsewogue girls’ varsity and junior varsity field hockey teams were also at the event. While many of them were dancing to the music there, they also donated money and helped organize the buckets for people to dump water on themselves or others during the ice bucket challenge. The buckets were arranged at the end of the event to spell out “ICE ALS.”

“The goal is to have this and other events that Ride For Life supports and make them bigger and better,” Manzoni said.

Although he did not know how much money the group raised this year, Manzoni hoped it matched or exceeded the amount of money raised last year, $5,000. He added that successful research into ALS can also help research for Alzheimer’s and Parkinson’s disease, which are more common but have similarities.

According to the ALS Association’s website, the disease affects around 6,400 people annually in the United States alone. Only 10 percent of people who are diagnosed with the disease inherited it, while the rest are affected by the disease at random.

For people and organizations like Ride For Life, these events are important.

The goal is “to build awareness and money so that we can continue [our efforts],” Manzoni said.

by -
0 427
Participants dump buckets of ice water over their heads during last year’s event. File photo by Erika Karp

This challenge can’t get much colder, and for the second year in a row, Mount Sinai is looking for help icing amyotrophic lateral sclerosis.

Last year, 500 participants from all over the North Shore came out to Heritage Park in Mount Sinai for the Ride for Life Ice ALS challenge, to raise money to help spread awareness and find a cure for ALS.

The disease affects nerve cells in the brain and spinal cord, causing motor neurons to degenerate. People with the disease lose control over their muscles, leaving them unable to speak, eat, move or breathe on their own.

With events like the one at Heritage Park, people all over the world have brought attention to ALS, and on Aug. 26, Mount Sinai is doing it again.

Game booths, face painting, balloon twisting, dunk tanks and pie tosses are just a few of the events listed for Wednesday’s ice bucket challenge. Admission to the event, which begins at 5 p.m., is free, and T-shirts and other ALS awareness items will be available for purchase. Hot dogs, cotton candy and soda will also be available, as well as a limited supply of buckets.

To help support the cause, create a team or collect pledges for the Big Dump, which will begin promptly at 7 p.m.

“Last year, more than 500 people participated in the challenge and I expect to see a bigger crowd this year,” Councilwoman Jane Bonner (C-Rocky Point) said in a press release. “We need all the help we can get from friends, family, businesses, sports teams and more to come together so we can find a cure for ALS.”

Paper pledge forms can be found on www.alsrideforlife.org. In the event of bad weather, a rain date is scheduled for Sept. 2. Email RFLoffice21@aol.com or go to Facebook’s ALS Ride for Life page for more information.

Social

4,795FansLike
5Subscribers+1
983FollowersFollow
19SubscribersSubscribe