CLOSE
Tags Posts tagged with "Power of 3"

Power of 3

by -
0 534

By Daniel Dunaief

 

Adrian Krainer with Emma Larson earlier this year. Photo from Dianne Larson

The prognosis hit Dianne Larson of Middle Island hard. Within three weeks, anxiety attacks, a lack of sleep and fear caused her weight to plummet from 135 to 120 pounds. She found out her daughter Emma, who was 17 months old at the time, had a potentially fatal genetic condition called spinal muscular atrophy in which the motor nerve cells of the spinal cord progressively weaken. Normally, the SMN1 gene produces the survival of motor neuron protein, which, as its name suggests, helps maintain motor neurons. People with SMA, which has four types and severity, produce a lower amount of the functional protein.

“My mind went to the darkest of dark places,” said Larson, whose daughter couldn’t crawl or sit up to eat. “There was no hope. There was nothing I could do.”

At the time of Emma’s diagnosis, there was no treatment for a disease that is the leading genetic cause of death among infants and affects about 1 in 10,000 newborns. Thanks to the work of Adrian Krainer, a professor and program chair of cancer and molecular biology at Cold Spring Harbor Laboratory, that changed early enough to alter the expectations for Emma and children around the world battling a genetic condition that causes progressive weakness and can make moving and even breathing difficult.

Turning to a back up gene called SMN2, Krainer hoped to fix a problem with the way that gene is spliced. On SMN2, exon 7 is normally skipped and the resulting protein has a different sequence at the end. Krainer developed an antisense olignocleotide that binds to a sequence in the intro following exon 7, blocking the splicing receptor. The treatment, which is called Spinraza, helps guide the splicing machinery, which carries out one of the steps in gene expression that is necessary to build a functional protein.

The Larson family of Middle Island, from left, Dianne, Emma and Matthew. Photo from Dianne Larson

Larson had heard of Krainer’s work and was eager to see if his success with animal models of the disease would translate for humans. As soon as Emma reached her second birthday, Larson enrolled her daughter in a clinical trial for Spinraza. After her daughter had a few shots, Larson was stunned by the change. “I was in the master bedroom and she was in the den and I heard a voice getting closer,” Larson recalls. “Next thing I know, she was in my bedroom. I couldn’t believe she crawled from the den to the bedroom. I put her in the den and told her to do it again,” which she did.

The SMA community and Krainer received an early holiday present in late December when the Food and Drug Administration not only approved the treatment, but it also gave doctors the green light to prescribe it for all types of SMA and for patients of all ages. While the SMA community, doctors and Krainer have been delighted with the FDA approval, the excitement has been tempered by concerns about the price tag Biogen, which manufactures and commercializes Spinraza and funded the drug’s development, has placed on the treatment.

For the first full year of injections, the drug costs $750,000. Every year after that will cost $375,000, which Biogen has said publicly is consistent with the pricing for other drugs for so-called orphan diseases, which affect a much smaller percentage of the population.

Knowledge Ecology International, a nonprofit advocate for affordable medicines, sent a letter to the Office of the Inspector General at the Department of Health and Human Services, seeking an investigation. The letter claims that the inventor and maker of Spinraza failed to disclose that the treatment received federal funding. KEI urges the government to use that alleged disclosure failure to end the patent and authorize a generic manufacture of the treatment.

Biogen didn’t return a call and email for comment. Patients and their families, meanwhile, are looking for immediate access to a life-altering treatment. “To be honest, I really don’t know what we’re going to do,” said Larson, whose daughter has four injections left as part of the extension trial soon. “I’m hoping insurance will cover it.”

Insurer Anthem announced late in January that the treatment was only medically necessary for patients with Type 1 SMA, which include people diagnosed with the disease within six months of birth. Anthem created a pay for performance model, which will require patients or their families to prove that the treatment is improving the lives of the recipients.

Larson said she has been in touch with a personal liaison at Biogen, which has been “helpful and supportive,” she said. “They have been going out of their way to reach out to the community to make sure everyone gets access.”

Larson, who is a financial advisor, said she understands the need for the company to generate a profit. “A lot of money goes into” research and development Larson said. “If they’re not gong to make money, they’re not going to” support the efforts to create a treatment.

Emma Larson will be turning 4 this month. Photo from Dianne Larson

Joe Slay, who is the chairman of FightSMA, a group he and his wife Martha founded in 1991 after they learned their son Andrew had Type 2 SMA, sounded hopeful that people who need this treatment will receive it. “I understand there’s constructive, good conversations between insurance companies and Biogen,” Slay said. “We’re monitoring that.”

While Andrew, who is now 30, considers the potential benefits of Spinraza, Slay is pleased the treatment is an option for people and is proud of Krainer’s work.Krainer is “by any definition of the word a hero,” Slay said. “He’s taken his natural gifts, his brilliance in science, his discipline year in and year out approach to his work and has applied himself 100 percent.”

Slay and FightSMA, which has raised over $8 million since its founding, helped provide seed money to Krainer more than 15 years ago, attracting a promising scientist to what was then an intractable medical challenge.

Tom Maniatis, who is the chairman of the Department of Biochemistry and Molecular Biophysics at Columbia University, said Krainer, who did his doctoral work in Maniatis’s lab, showed considerable scientific promise early in his career. Krainer “clearly had the intelligence, drive and experimental skills to make important contributions,” Maniatis said. His work is “a perfect example of how deep basic science studies can lead to profound understanding of a disease mechanism and that, in turn to the development of a treatment,” explained Maniatis in an email.

Within Krainer’s own family, there is a connection to patient care. Krainer’s daughter Emily, who is a pediatric neurology resident at Rochester, may one day prescribe a treatment her father developed. “It will be quite something for me if she eventually prescribes Spinraza to one of her patients,” Krainer said. Even as other scientists and companies like AveXis continue to search for ways to treat SMA, Krainer enhances and refines his research.

“We continue to work on understanding aspects of SMA pathophysiology, the role of SMN levels outside the central nervous system and the potential for prenatal therapy,” he explained in an email. “We are also working on antisense therapies for other genetic diseases and cancer.”

Larson, who is overjoyed with her daughter’s progress, calls Krainer her “superhero” who “saved my daughter’s life.” “It’s such a different feeling when you know you can do something,” she said. When she found out that the FDA approved the treatment, it was “the best day.”

by -
0 2092

By Daniel Dunaief

Born in Berlin just before World War II, Eckard Wimmer has dedicated himself in the last 20 years to producing something that would benefit humankind. A distinguished professor in molecular genetics and microbiology at Stony Brook University, Wimmer is hoping to produce vaccines to prevent the spread of viruses ranging from influenza, to Zika, to dengue fever, each of which can have significant health consequences for people around the world.

Using the latest technology, Wimmer, Steffen Mueller and J. Robert Coleman started a company called Codagenix in Melville. They aim to use software to alter the genes of viruses to make vaccines. “The technology we developed is unique,” said Wimmer, who serves as senior scientific advisor and co-founder of the new company.

Mueller is the president and chief science officer and Coleman is the chief operating officer. Both worked for years in Wimmer’s lab. Despite the potential to create vaccines that could treat people around the world facing the prospect of debilitating illnesses, Wimmer and his collaborators weren’t able to attract a pharmaceutical company willing to invest in a new technology that, he estimates, will take millions of dollars to figure out its value.“Nobody with a lot of money may want to take the risk, so we overcame that barrier right now,” he said.

Eckard Wimmer in his lab. Photo by Naif Mohammed Almojarthi

Codagenix has $6.2 million in funding. The National Institutes of Health initially contributed $600,000. The company scored an additional $1.4 million from NIH. It also raised $4.2 million from venture capital, which includes $4 million from TopSpin and $100,000 from Accelerate Long Island and a similar amount from the Center for Biotechnology at Stony Brook University.

Stony Brook University recently entered an exclusive licensing agreement with Codagenix to commercialize this viral vaccine platform. Codagenix is scheduled to begin phase I trials on a vaccine for seasonal influenza this year.

The key to this technology came from a SBU collaboration that included Wimmer, Bruce Futcher in the Department of Molecular Genetics & Microbiology and Steven Skiena in the Department of Computer Science. The team figured out a way to use gene manipulation and computer algorithms to alter the genes in a virus. The change weakens the virus, giving the attack dog elements of the immune system a strong scent to seek out and destroy any real viruses in the event of exposure.

Wimmer explained that the process starts with a thorough analysis of a virus’s genes. Once scientists determine the genetic code, they can introduce hundreds or even thousands of changes in the nucleic acids that make up the sequence. A computer helps select the areas to alter, which is a rapid process and, in a computer model, can take only one afternoon. From there, the researchers conduct experiments in tissue culture cells and then move on to experiment on animals, typically mice. This can take six months, which is a short time compared to the classical way, Wimmer said.

At this point, Codagenix has a collaboration with the Universidad de Puerto Rico at the Caribbean Primate Research Center to treat dengue and Zika virus in primates. To be sure, some promising vaccines in the past have been taken off the market because of unexpected side effects or even because they have become ineffective after the virus in the vaccine undergoes mutations that return it to its pathogenic state. Wimmer believes this is unlikely because he is introducing 1,000 changes within a vaccine candidate, which is much higher than other vaccines. In 2000, for example, it was discovered that the polio vaccines involve only five to 50 mutations and that these viruses had a propensity to revert, which was rare, to the type that could cause polio.

Colleagues suggested that this technique was promising. “This approach, given that numerous mutations are involved, has the advantage of both attenuation and genetic stability of the attenuated phenotype,” Charles Rice, the Maurice R. and Corrine P. Greenberg professor in virology at Rockefeller University explained in an email.

While Wimmer is changing the genome, he is not altering the structure of the proteins the attenuated virus produces, which is exactly the same as the virus. This gives the immune system a target it can recognize and destroy that is specific to the virus. Wimmer and his associates are monitoring the effect of the vaccines on mosquitoes that carry and transmit them to humans. “It’s not that we worry about the mosquito getting sick,” he said. “We have to worry whether the mosquito can propagate this virus better than before.” Preliminary results show that this is not the case, he said.

Wimmer said there are many safety precautions the company is taking, including ensuring that the vaccine candidate is safe to administer to humans. Wimmer moved from Berlin to Saxony after his father died when Wimmer was 3. He earned an undergraduate degree in chemistry in 1956 at the University of Rockstock. When he was working on his second postdoctoral fellowship at the University of British Columbia in Vancouver, he heard a talk on viruses, which brought him into the field.

A resident of Old Field, Wimmer lives with his wife Astrid, a retired English professor at Stony Brook. The couple’s daughter Susanne lives in New Hampshire and has three children, while their son Thomas lives in Portland, Oregon, and has one child. “We’re very happy Long Islanders,” said Wimmer, who likes to be near the ocean and Manhattan.

Through a career spanning over 50 years, Wimmer has won numerous awards and distinctions. He demonstrated the chemical structure of the polio genome and worked on polio pathogenesis and human receptor for polio. He also published the first cell-free creation of a virus.

“This was an amazing result that enabled a number of important mechanistic studies on poliovirus replication,” Rice explained. Wimmer has “always been fearless and innovative, with great enthusiasm for virology and discovery.”

With this new effort, Wimmer feels he will continue in his quest to contributing to humanity.

by -
0 2131
From left, Robert Catell, chairman of the board, Advanced Energy Research and Technology Center; Vyacheslov Solovyov; Sergey Gelman, a Stony Brook engineering student; and Yacov Shamash, vice president for economic development at Stony Brook University. Photo from Stony Brook University

By Daniel Dunaief

It’s lighter, cheaper and just as strong. In the age of manufacturing the latest and greatest high-technology parts, that is a compelling combination. Indeed, the Department of Energy recently awarded the Brookhaven Technology Group, a business incubator tenant of the Advanced Energy Research and Technology Center at Stony Brook University, $1.15 million to develop a high-temperature superconductor cable with a new architecture. The grant supports the research of Vyacheslav Solovyov, an adjunct professor in the Department of Electrical Engineering at SBU and the principal investigator at Brookhaven Technology Group.

“Very few projects are funded, so we’re very excited that ours was chosen,” said Paul Farrell, the president at BTG. The potential applications for Solovyov’s Exocable, as the new architecture is called, span a wide range of uses, including in high field magnets for a new breed of accelerator. The work entails creating a high-temperature superconducting cable that is an integral ingredient in creating the superconducting machinery. The BTG process produces a high-temperature superconducting cable after removing the substrate, which is a single-crystal-like material. Solovyov transfers the superconducting layer to a supporting tape that can be engineered for strength and not for crystallinity.

This work reduces the weight of the tape by as much as 70 percent per unit length for the same current capacity. The potential for this new cable is that it can contribute to the growing field of research at Stony Brook and Brookhaven National Laboratory on superconductivity, said Jim Smith, assistant vice president of economic development at Stony Brook. “Maybe this is the next industry that replaces the Grummans and the aerospaces that have left,” he said. Semiconductors are of particular interest to manufacturers because they transmit energy with no resistance. Right now, about 6.5 percent of energy transmitted around the United States is lost in distribution wires, Smith said. Maintaining the energy that’s lost in the wires would have “tremendous benefits.”

To be sure, while the research at BTG could contribute to lower cost and improved efficiency in high-temperature superconductivity, there are hurdles to making this process and the applications of it work. For starters, the company needs to produce kilometers of ExoCable. “The challenge is to demonstrate that the properties will be as uniform as they were before the substrate removal,” explained Solovyov, who has been working in superconductivity since 1986.

Recently, Smith said he, Farrell and Solovyov met to discuss the wiring for their facility. “A lot of power and wiring will be installed in the next four to five weeks,” Smith said. Scientists who worked with Solovyov expressed admiration for his work and optimism about his results. Solovyov’s “new activity will definitely advance the long-promised practical application of superconductivity electrical power transmission, as well as in the development of high-field magnets for both industrial and scientific application,” David Welch, a former collaborator and retired senior materials scientist at Brookhaven National Laboratory, wrote in an email. Welch explained that Solovyov focused on methods for making composites of superconducting material with normally conducting metals in the form of wires, tapes and cables necessary for their practical application. “Such a combination of talents is unusual,” Welch continued. Early on, it was clear “that [Solovyov] was going to become an important member of the scientific staff at BNL.”

Solovyov started working on this process with BTG about a year and a half ago. When he first started collaborating with BTG, the company was working on a superconducting project funded by the army. When that work ended, Solovyov and BTG worked together to submit new proposals to the DOE. According to Solovyov, Stony Brook has been “very helpful in terms of providing facilities and lab space.” Stony Brook’s goal, Smith said, is to help companies like BTG succeed and measures that success in the number of new jobs created in the energy field.

Solovyov, who grew up in the Ukraine, said he has had several breakthroughs in his career. He helped develop a patented technology that can speed up the processing of superconducting materials by a factor of 10. “That has been used in production and I’m very proud of it,” Solovyov said. The professor lives in Rocky Point with his wife Olena Rybak and their two children, Natasha, 19, who attends Suffolk County Community College, and Dennis, 14, who is in high school. Solovyov said he enjoys Long Island, where he can fish for striped bass and bluefish. He pan fries what he catches.

As for his work, Solovyov has four patents and applications for three more. He and Farrell said the company is looking for opportunities for expansion. He is exploring ways to work with large-scale generators and wind turbines. Farrell explained that BTG has ambitions to become a larger company. BTG would “like to become a major contributor in this field,” Farrell said. That could include adding staff and developing more products that can be sold and used worldwide. “If our product is successful, in the sense that it improves the capability of superconductors to be used commercially, we’ll be adding people.” This work will need more funding, which the company plans to get either from the Department of Energy, from private investors or both.

“If you can improve the usefulness of superconductors and reduce the cost of the wire, there’ll be wider use than there is right now,” Farrell said.

Prev1...363738Page 38 of 38
TBR News Media is your local news and entertainment website.
We provide you with the latest breaking news and information for your community.
Contact us: [email protected]

Most Viewed

©