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Lung Transplant Recipient Thanks 'true Hero' Donor

Gill Dummigan

North West Health Correspondent, BBC News

The first time I meet Sam Atherton he is sitting beside his hospital bed, waiting to hear whether he's about to get a lung transplant which could save his life.

The 48-year-old is in the late stages of pulmonary fibrosis – a degenerative and often fatal lung disease which has left him continually struggling for breath.

He can only function with the help of a constant flow of oxygen from a tank beside him.

"I know it needs to happen," he says of the transplant. "You look at this disease, you read about it, and your life expectancy is not long.

"It's got worse over the past few months and particularly the past six weeks or so... It's quite scary when you can't breathe."

Around him sit his three children – Connor, 26, Ethan, 22, and Ellie, 20, and his wife Nic.

"I'm under no illusion that I might wake up one morning and I don't have a husband any more and my children don't have a father," says Nic.

"So we need to do everything we can to make sure that does not happen."

Sam has been called into the Transplant Centre at Wythenshawe Hospital in Manchester because he is thought to be a good match for a donor today.

Wythenshawe is one of only six centres in the UK which carries out heart and lung transplants on adults.

Image caption,

Sam's life is in the hands of consultant lung surgeon Vasudev Pai (centre) and team

While Sam waits nervously, endless messages and phone calls go back and forth between the team at Wythenshawe and the surgical retrieval specialists waiting at the donor's hospital to assess the suitability of the lungs for Sam.

Recipient patient co-ordinator Jane Nuttall's job is to make sure everything runs smoothly – from booking operating theatres in both the donor and recipient hospitals to ensuring the surgical teams are in synch.

Jane tells me the retrieval team, who are with the donor, have just sent images from a bronchoscopy, a camera which goes down into the lungs.

"So far all looks good," she says. "We've had an image sent to us, and myself and the surgeon, we're happy with that."

'Fingers crossed'

The retrieval team will now physically look at the lungs and carry out a series of tests.

At any point they may discover the lungs are are not suitable for transplant.

"Sometimes there's injury, there's trauma if the donor's been involved in a road traffic accident, sometimes there's infection," Jane explains.

Sam's been here before: last July he was called in after another match.

"I was gowned, shaved," he said. "They just came into the room and said 'Sorry it's not going to go ahead'.

"I'm just hoping I'm not going to get back into the car and go home today so yes, fingers crossed, everything crossed.

"And pray for the donor as well. Because someone's had to lose their life for me to gain some lungs."

Image caption,

The donors' lungs are rushed into the operating theatre

Eventually Jane comes into the ward.

"I'm coming with some very good news," she says. "It's going to go ahead."

Sam looks slightly dazed. Nic runs over to her husband, hugs him and sheds a few tears.

Within the hour he is on his way to the operating theatre, having said goodbye to his children. Nic stays with him until he's put under.

"I just want him to have a lung transplant and have the best chance of living, and carrying on and watch his children grow," she tells me. "This man has now got a chance of life."

By now it is late evening, but the surgical team has the whole night ahead of it. A double lung transplant can take up to 12 hours to perform.

Image caption,

Teamwork and attention to detail is absolutely vital

Sam's consultant lung surgeon Vasudev Pai says this type of operation calls for resilience from the whole team.

"You have to keep concentrating, with attention to detail, all the time," he says.

Because the operation takes so long, the surgical team begins while the donor lungs are still en route.

Once they arrive in a freezer box, the first of Sam's lungs can be completely removed.

They will be replaced one at a time, while Sam's blood is run through an ECMO (extra-corporeal membrane oxygenation) machine to keep it oxygenated during surgery.

Mr Pai says taking out the old lung can be particularly difficult.

"That's the crucial stage. If you miss out some small branches and it keeps bleeding post operatively, you can't see.

"Once you've put the new lung in, to go back in and find all these things is very tough."

Even though the size of donor and recipient is one of the many factors taken into account, Mr Pai says there is always a slight difference.

"The lung is always slightly big or slightly small so you have to size it to fit it in... Technically it's quite a challenging thing to do."

While Sam's operation finally finishes at 9am, the waiting continues for Sam's family.

He has to be kept unconscious for a further three days to keep him stable while the medical team monitors his new lungs.

'A true hero' Image source, Sam Atherton Image caption,

Sam is incredibly grateful to the person who has given him another shot at life

By day six, when we next meet, there's positive news.

Sam is already getting out of his chair for physiotherapy.

"The first day I got out of bed was painful," he reveals.

"All the physios, the nurses, they're really good. They push you but you need to be pushed, and push yourself as well.

"They say I'm progressing very well… every day's a better day."

Three-and-a-half weeks after his operation, Sam is out of hospital and recovering at home.

He will spend the first three months being regularly monitored and tested for any signs of infection or rejection of his new lungs.

For the rest of his life Sam will have to take a cocktail of medication: he tells me he is currently on 65 tablets a day, although this will decrease.

His immune system has to be permanently weakened to stop it from attacking his new lungs, leaving him vulnerable to infections and even certain types of skin cancer.

But for Sam, all of that is a small price to pay.

"Knowing that I'm going to be here for my family, knowing that I don't need to worry about not being here... And that my wife and kids will have to do things without me," he says.

A tear wells up and runs down Sam's cheek. Wiping it away, he continues: "No money in the world can give me what that donor gave to me. My donor is a true hero."

Rare Lung Disease: Genetics Reveals Cause Of PCD

These exciting and unexpected insights into ciliopathies were only possible due to the collaborative partnership between the patients in our studies, their clinicians and researchers with interdisciplinary expertise from across the world

Pleasantine Mill

Mutations in over 50 genes account for 70% of PCD cases, with the remainder of cases unexplained. Using next-generation DNA sequencing approaches, researchers were surprised to find recurrent mutations in the beta-tubulin gene TUBB4B, in twelve different PCD patients, that were not found in their parents. Moreover, where on the TUBB4B protein these recurrent mutations were found resulted in very different clinical presentations.

TUBB4B is one of the building blocks of microtubules – scaffold-like structures involved in cell shape, movement, and cell division and critical for cilia formation. Each link of the tubulin 'chain' is composed of one alpha and one beta tubulin protein. Humans have 10 types of beta tubulin, including TUBB4B. The different tubulin subunits seem to not be interchangeable and may have different roles as mutations in one, such as TUBB4B, cannot be always compensated for by the others.

Researchers used both computational and laboratory-based approaches to resolve how mutations in different parts of the TUBB4B molecule differently affect how the tubulin building blocks assemble and disrupt cilia form or function. They found mutations at different interfaces between tubulin links result in different patient outcomes, such as early vision loss, lung disease, or both conditions simultaneously. The researchers were able to show that one mutant copy of TUBB4B was capable of over-riding the healthy copy to disrupt microtubule and cilia formation, a phenomenon called the 'dominant negative' effect, previously not observed in PCD.

In addition to improving the diagnosis and genetic counselling of PCD patients and their families, this novel disease mechanism will require different therapeutic strategies to treat these patients. "These exciting and unexpected insights into ciliopathies were only possible due to the collaborative partnership between the patients in our studies, their clinicians and researchers with interdisciplinary expertise from across the world," said Professor Pleasantine Mill, Chair of Cilia Biology at the University of Edinburgh, who co-led the study. Study authors Mill, Shoemark and Mitchison are co-leads, with other UK researchers, for a newly funded £9.4M UK-wide LifeArc Centre for Rare Respiratory Diseases, which aims to improve molecular diagnoses as well accelerate molecular insights to develop new therapies for rare lung diseases, like PCD.

"We know firsthand the unmet need from significant burden of disease for rare lung diseases like PCD. We hope this work and our newly funded collaborative centre will provide the foundation to raise awareness, develop much-needed treatments and use them to benefit these patients," added Prof. Amelia Shoemark.

Source: University of Edinburgh

Anti-aging Human Tests Begin – And $40 Million Of Funding Is Behind It

"As people live longer, improving quality of life is paramount," said Alex Morgan, a partner at Khosla Ventures, who chipped in to fund Rubedo's first round of venture capital financing. "Rubedo is targeting senescent, or aging, cells that drive age-related disease. This first trial can bring us another step closer to achieving better healthspan."

Senescent cells age and permanently stop dividing, but they don't die. Over time, they accumulate in the tissues and release high levels of inflammatory chemicals and immune modulators that contribute to aging.

Rubedo plans first to undertake Phase 1 studies to assess RLS-1469's effectiveness in treating incurable inflammatory skin conditions, chronic atopic dermatitis and chronic psoriasis. Pre-clinical data showed that the drug significantly reduced senescent cells in the skin that drive these chronic degenerative conditions and it's hoped that RLS-1469 will provide long-term relief to patients with them.

Rubedo's drug, RLS-1469, is designed to treat chronic skin conditions like psoriasis

"Our mission is to invest in transformational companies that will change the world for the better, serving vast markets," said Alice Newcombe Ellis, founding and general partner of Ahren Innovation Capital, another contributor. "We believe that Rubedo's transformative approach to targeting senescent cells is an impressive step towards the development of chronic age-related therapies, which will advance biotech from treatment to prevention or disease reversal."

Rubedo is also developing other therapies that selectively target senescent cells in pulmonary disease, filling an unmet medical need. Its team are very grateful for the support, financial and otherwise, that they've received from their backers.

"The significant experience and capital that our investors bring to Rubedo will help the company rapidly advance our programs," said Ali Siam, chief business officer at Rubedo Life Sciences. "We look forward to working with these leaders, whose vast experience in clinical development will be invaluable as we enter the next phase of growth at Rubedo."

Rubedo's proprietary AI-augmented drug discovery platform, Alembic, identifies specific druggable targets for development into disease-modifying therapeutics.

Source: Business Wire

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