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Genetically Modified Pig's Heart Is Transplanted Into A Second Patient

Surgeons in Baltimore have transplanted the heart of a genetically altered pig into a man with terminal heart disease who had no other hope for treatment, the University of Maryland Medical Center announced on Friday.

It is the second such procedure performed by the surgeons. The first patient, David Bennett, 57, died two months after his transplant, but the pig heart functioned well and there were no signs of acute organ rejection, a major risk in such procedures.

The second patient, Lawrence Faucette, 58, a Navy veteran and married father of two in Frederick, Md., underwent the transplant surgery on Wednesday and is "recovering well and communicating with his loved ones," the medical center said in a statement.

Mr. Faucette, who had terminal heart disease and other complicated medical conditions, was so sick that he had been rejected from all transplant programs that use human donor organs.

"At least now I have hope and I have a chance," Mr. Faucette said before the surgery. "I will fight tooth and nail for every breath I can take."

The transplantation was performed by Dr. Bartley Griffith, who operated on the first patient. Dr. Muhammad Mohiuddin, of the University of Maryland School of Medicine, designed the protocol.

Mr. Bennett died after multiple complications, and traces of a virus that infects pigs were found in his new heart, raising concerns that so-called xenotransplants of organs from animals to people could introduce new pathogens into the human population.

Hospital officials said they repeatedly tested the pig used in the transplant last week for both the virus, called porcine cytomegalovirus, and antibodies using a new assay that was not available at the time of Mr. Bennett's transplant.

Before undergoing the transplant, Mr. Faucette said he recognized that it would be a miracle if he was able to leave the hospital and go home, and another miracle if he lived for months or a year longer.

"Realistically, this is in the early-stage learning process," he said of the procedure.

In recent years, the science of xenotransplantation has taken huge strides with gene editing and cloning technologies designed to make animal organs less likely to be rejected by the human immune system.

Although the advances are still in nascent stages, they offer hope to the more than 100,000 Americans who are living with end-stage organ disease yet face an acute shortage of human donor organs. Most of those waiting for an organ need a kidney, but fewer than 25,000 kidney transplants are performed each year and thousands die on waiting lists.

Transplant surgeons at the University of Alabama at Birmingham and NYU Langone Health have transplanted kidneys from genetically modified pigs into brain-dead patients maintained on ventilators, demonstrating that the kidneys can make urine and perform other essential biological functions without being rejected.

"There is a growing need for organs and for people with end-stage organ failure who are out of options," said Dr. Jay Fishman, a professor of medicine at Harvard and associate director of the Transplant Center at Massachusetts General Hospital.

"While decedent trials are informative, transplants in living recipients are, of course, most relevant to advancing knowledge in the field," Dr. Fishman added. He said he was optimistic that the surgery would encourage scientists to enter the field and accelerate the path to clinical trials.

The heart transplanted into Mr. Faucette came from a pig that had received 10 genetic modifications. Scientists removed three pig genes that cause rapid rejection of pig organs by the human immune system, while inserting six human genes that allow the immune system to accept the organ.

An additional pig gene, responsible for the heart's growth, was knocked out to prevent the organ from becoming too large.

The genetically altered pig was provided by Revivicor, a regenerative medicine company based in Blacksburg, Va., that is a subsidiary of United Therapeutics Corporation. Before the transplant, the pig was screened for viruses, bacteria and parasites.

The Food and Drug Administration granted emergency approval to the transplant last week under a "compassionate use" process that allows experimental procedures to be performed on a single patient who has a life-threatening condition.

Mr. Faucette is also receiving an experimental new antibody therapy developed by Eledon Pharmaceuticals called tegoprubart, which blocks a protein involved in the activation of the immune system. Other conventional drugs are also being used to suppress his immune system and prevent rejection of the organ.

Mr. Faucette's wife, Ann, said the two were keeping expectations low and just hoping for some more time together. "That could be as simple as sitting on the front porch and having coffee together," she said.

Researchers Say Chemo Drug May Prevent Heart Failure

A chemotherapy drug used to fight bone-marrow cancer has the potential to treat and prevent potentially deadly heart failure, a powerful new drug-screening tool developed at UVA Health suggests.

The tool was created by University of Virginia researchers Jeffrey J. Saucerman and graduate student Taylor G. Eggertsen. The sophisticated computer model suggested the drug midostaurin could help prevent the enlargement of heart muscle cells that often precedes heart failure. Subsequent lab results bore that out.

While additional human testing is needed, Saucerman says the new computer model has demonstrated great potential for identifying already available drugs that can be repurposed to battle heart failure, a condition affecting millions of Americans.

"This new computer tool helps us find new uses for old drugs, and it also explains how they may work in the heart," Saucerman said. "New drugs take decades to develop. We hope this tool will help us find drugs for heart failure that are already known to be safe and effective for other diseases."

The researchers have published their findings in the British Journal of Pharmacology.

Heart failure is a progressive condition that grows worse with time. The heart loses the ability to pump blood, which can lead to fatigue, wheezing, weakness, swollen legs and feet and, ultimately, death.

While there are drugs used to treat heart failure, more than half of people with the condition die within five years of diagnosis. That speaks to how urgently new and better treatments are needed.

With that in mind, Saucerman and Eggertsen created a complex computer model of the harmful growth of heart muscle cells prior to heart failure. This model allowed them to run sophisticated simulations demonstrating how existing drugs would affect the process known as cardiac hypertrophy.

"This approach has identified a number of drugs that show initial promise for heart disease that we would not have suspected," Eggertsen said.

The researchers screened more than 250 candidate drugs and found 38 that slowed the harmful heart changes. In addition, the model let the scientists understand how the drugs were having this effect, helping the researchers narrow their options. They then tested the most promising drugs in heart muscle cells. They ultimately found that midostaurin, a chemotherapy drug used to treat acute myeloid leukemia, a cancer of the blood and bone marrow, had the potential to slow the damaging changes to the heart.

"Now that we have found interesting drugs in computer simulations and heart muscle cells, we plan to test these drugs in experimental models that are more similar to humans," said Saucerman, who is part of UVA's Department of Biomedical Engineering, a joint program of the School of Medicine and School of Engineering.

"This computational treasure hunt for drugs may eventually lead to more options for treating heart failure patients," he said.

More information: Taylor G. Eggertsen et al, Virtual drug screen reveals context‐dependent inhibition of cardiomyocyte hypertrophy, British Journal of Pharmacology (2023). DOI: 10.1111/bph.16163

Citation: Researchers say chemo drug may prevent heart failure (2023, September 18) retrieved 23 September 2023 from https://medicalxpress.Com/news/2023-09-chemo-drug-heart-failure.Html

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Global Cases Of Heart Failure To Exceed 16 Mn By 2032: Report

The diagnosed prevalent cases of heart failure are set to register an annual growth rate of 1.68 per cent from 13.76 million in 2022 to 16.07 million in 2032, according to a report on Friday, 22 September.

The report by GlobalData, a leading data and analytics company, showed that the rise will particularly be seen in the seven major markets -- the US, France, Germany, Italy, Spain, the UK, and Japan.

The report reveals that in 2032, the US will have the highest number of diagnosed prevalent cases of heart failure among these countries at 7.35 million cases, whereas Spain, with nearly 0.77 million cases, will have the lowest number.

"Both men and women can be affected, however heart failure is more prevalent among men and in the elderly population," said Antara Bhattacharya, Associate Project Manager from Pharma – Epidemiology team at GlobalData, in a statement.

Adults ages 60 years and above accounted for almost 85 per cent of the diagnosed prevalent cases of heart failure in the seven countries while those in younger adults ages 19–59 years accounted for almost 14 per cent of the cases.

Children aged 18 years and younger accounted for 0.37 per cent of the cases. This is apparent from GlobalData estimates for age-specific diagnosed prevalent cases.

Heart failure with preserved ejection fraction -- a form of heart failure -- accounted for approximately 47 per cent of the diagnosed prevalent cases of heart failure in the seven countries in 2022.

"There is an increased need for individualisation of in-hospital management, including treatments targeting the causative factors, and continuation of treatment after hospital discharge to improve long-term outcomes especially for acute heart failure," Bhattacharya said.

"The case mix of heart failure is evolving, more epidemiological data on acute heart failure can improve the treatment outcomes. With early diagnosis and lifestyle modifications, more people with heart failure can perform well.

"With respect to heart failure treatment, awareness among physicians, and obtaining the optimal management for heart failure patients while preventing underutilisation, or suboptimal dosing of guideline-directed medical therapy is necessary for improving functional status, quality of life, and survival in patients with heart failure," she added.

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