ItHome Cardiac Arrest Ellsworth company developing a drug to stimulate damaged heart tissue

Ellsworth company developing a drug to stimulate damaged heart tissue

Credits to the 👉🏾Source Link👉🏾 Olivia
Ellsworth company developing a drug to stimulate damaged heart tissue

ELLSWORTH — A company seeking to develop a drug that could help stimulate the formation of new heart muscle after an acute heart attack has moved its laboratory into the Union River Center for Innovation (URCI) on Water Street.

Novo Biosciences, a seven-year-old, for-profit spinoff company of the MDI Biological Laboratory, is run by Voot P. Yin and Kevin Strange, who, along with their collaborator Michael Zasloff, were granted a patent in 2016 for use of the small molecule MSI-1436, also known as Trodusquemine, to stimulate the repair and regeneration of heart tissue damaged by injuries such as a heart attack.

“If you look across all kinds of animals in nature, there are many animals that have profound capacity to repair and replace tissue after it’s been damaged or amputated,” said Strange. “If they lose a limb, they grow it right back. If their spinal cord is severed, they heal it right up just fine. If their brain is damaged, they repair it without question. If there’s any sort of heart damage, whether we do it experimentally to them or it happens naturally, they repair that quite readily.

“So the approach we have here is to look at these animals, study them intensely, and ask a very basic question: ‘How do these animals accomplish this amazing feat and why is it, for the most part, that most of our tissue — our heart, our spinal cord, our brain, for example — don’t regenerate after an injury?’”

Humans have the ability to repair injured tissues “encoded in our genomic material, our DNA,” said Yin. But while some tissues (the skin, the lining of the gut) are constantly regenerating, many others lose that capacity. Right now, heart muscle damaged by a heart attack may scar over, but the muscle will be left permanently damaged, which can interfere with the heart’s function and eventually lead to heart failure. Yin and Strange are hoping that MSI-1436 can “reactivate those pathways” that help regenerate and repair tissue, said Yin.

The molecule has already shown great promise. A natural compound initially discovered by Michael Zasloff, Yin acted on Zasloff’s hunch and tested MSI-1436 in zebrafish and then in mice, inducing heart attacks and then treating the damaged tissue with MSI-1436.

The results of that research were extraordinary: in both zebrafish and mice treated with MSI-1436, the animals’ hearts showed reduced scarring and the proliferation of heart muscle cells, as well as improved heart function and increased survival.

“We’re not simply blocking the formation of the scar, we’re actually allowing that initial scar that’s laid down to resolve itself, to be reabsorbed and replaced, presumably, with functional tissue,” Strange said in 2019.

It’s important, too, that MSI-1436 stimulates tissue regeneration in adult zebrafish and mice, which are separated by approximately 450 million years of evolution. That increases the likelihood the molecule will work in humans. The company received a $1.5 million Small Business Innovation Research grant from the National Institutes of Health in 2017 that allowed it to move ahead with studies of the effectiveness of MSI-1436 in pigs, whose hearts closely resemble those of humans.

If it works, there are other possibilities for the molecule, including to help regenerate skeletal and cardiac muscle tissues in patients suffering from Duchenne muscular dystrophy, a debilitating disease that causes progressive muscular degeneration in children. The average life expectancy for someone with Duchenne muscular dystrophy is just 26 years.

It’s not entirely clear why humans lose the ability to regenerate some tissues, said Strange, although he suspects it may be due in part to an immune response. And although much of the scientific community has been focused on stem cells as the holy grail of regenerative medicine, stem cell-based therapies have shown little efficacy in treating heart disease, the world’s leading cause of death, despite decades and billions of dollars of research, said Strange, who maintains that the intense focus on stem cells is “largely quackery when you actually look at it very carefully.”

“Repair and regeneration in response to both acute and chronic injury involves a very, very elegant series of highly-coordinated physiological processes,” Strange told a conference in 2019. That process includes not just stem cells but “a very elaborate immune response,” metabolic changes, the formation of new blood vessels and other physiological processes. “They all have to work together to give rise to effective repair of a damaged tissue,” Strange said.

Yin and Strange have moved their entire operation into the office on Water Street, where they conduct research in a 700-square-foot laboratory.

“It’s a fully functional laboratory with an animal vivarium, state-of-the-art imaging, molecule biology imaging,” said Yin. “It really provides us with everything we need to do the preclinical studies to advance MSI-1436 to Phase 1 clinical trials.”

Both men said that leaving academia to focus on their company full time has been a welcome shift, and that being around other entrepreneurs at the center has been invigorating.

“It’s been an absolute breath of fresh air,” said Yin. “I think one of the major things we’ve been able to do is design the laboratory space in a smart manner. Kevin and I are coming from academia, where there’s a lot of redundancy and waste in terms of space and resources. This is the absolute critical set of equipment and resources. There’s very little fat in how we run the operation.”

The company recently got $4 million in investment capital that will help it as it works to get the molecule ready for trials in humans, but that’s a drop in the bucket compared to what it costs to bring a drug to market, which can run into the many millions of dollars.

The average time it takes to get U.S. Food and Drug Administration approval for a drug is roughly 12 to 15 years, said Strange, from the time the molecule is identified. MSI-1436 has a bit of a leg up, as it has already shown to be well tolerated by patients in Phase 1 and 1b clinical trials (it was tested as an appetite suppressant in the early 2000s). The maximum well-tolerated human dose is 5 to 50 times higher than the dose shown to be effective in stimulating heart repair in zebrafish and mice. “It’s found to be safe in humans at concentrations that are about five times higher than the highest effective dose in our animal studies,” said Yin. “That’s a huge hurdle and obstacle we’ve been able to overcome.”

“That’s probably 10 years of work right there,” Strange said, adding that 99 percent of drugs under development “never see the light of day for patients,” and that the company will need tens of millions of dollars more in investment to get the molecule through clinical trials in humans.

Both men are quick to stress that the outcome of their research is far from certain and will take years to be fully understood.

“Maybe it never ends up in human patients,” said Yin, or “It may not help patients in the manner that we would predict. But this is such a rare discovery in one’s scientific career that we really do believe we have an obligation to push it as far as we possibly can.”

Kate covers the city of Ellsworth, including the Ellsworth School Department and the city police beat, as well as the towns of Amherst, Aurora, Eastbrook, Great Pond, Mariaville, Osborn, Otis and Waltham. She lives in Bar Harbor and welcomes story tips and ideas. She can be reached at [email protected]

Kate Cough

Source Link

related posts

Leave a Comment

This website uses cookies to improve your experience. We will assume you are ok with this, but you can opt-out if you wish. Accept Read More

%d bloggers like this: