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Irish Times
08-07-2025
- Health
- Irish Times
Genetic cures on demand: `Within four weeks, the vision in his eyes had doubled'
This year may prove to be an important year for advances in gene editing and gene therapies. But what does that really mean, and how have we got to this point? In what is claimed as a world first, doctors in the United States recently treated a baby with a rare genetic disease using a highly specific and personalised gene-editing technique . What did this involve and how is the baby doing? Baby boy KJ was born with a rare metabolic disease known as CPSI deficiency. This prevented his body from getting rid of ammonia during the metabolism of protein. And while he was put on a highly restricted protein diet and given drugs to remove protein from his blood, he remained at high risk of brain damage or even death. READ MORE Following the early diagnosis of KJ's condition, gene-editing researchers at the University of Philadelphia worked with colleagues throughout the US to quickly develop a personalised gene-editing infusion to correct a genetic variant that led to the disorder. KJ responded well to the three-dose regimen and is now reaching his developmental milestones. 'Ultimately, we hope this has set a precedent where we have firmly entered a world of genetic cures on demand,' said Fyodor Urnov, scientific director of the Innovative Genomic Institute in the University of California, Berkeley, a member of the treatment team. Have similar gene-editing techniques been used on patients in Ireland too and how do they differ from gene therapy? The gene-editing platform known as Crispr is widely used by researchers in scientific laboratories in their search for new therapies for cancer and other diseases. Essentially, Crispr – whose inventors won the Nobel Prize in chemistry in 2020 – is a cheap and efficient way of finding and altering specific pieces of DNA within cells. Clinical trials of gene therapies for inherited eye conditions are desperately needed for the treatment of an estimated 5,000 patients on the island of Ireland affected by these diseases — Dr Emma Duignan Gene therapy is slightly different in that it introduces new DNA materials into cells to replace or correct a gene or inactivate a target gene in the treatment of a specific disease. Earlier this year, ophthalmologic surgeon Dr Max Treacy treated 20-year-old Maros Tomko, who had severe visual loss since birth, with gene therapy at the Royal Victoria Eye and Ear Hospital in Dublin. The once-off treatment replaced the faulty gene RPE65 with a healthy copy. This was done via a viral vector which carried the healthy copy of the gene into the cells of the eye. 'Within four weeks, the vision in his eyes had doubled. From not being able to see any letters, he could read the first and second lines. His visual field [the total area seen] also doubled in size,' explains ophthalmologist Dr Emma Duignan. Tomko adds that he is very grateful to the doctors for this opportunity to have surgery. 'I can see people's faces now and I can read the numbers on my bank card for the first time. It's only three months since the surgery so it will take longer to get better,' he says. Ophthalmologist Dr Emma Duignan A 31-year-old Sligo man with a similar congenital blindness got his sight back after being treated with ocular gene therapy at the Mater hospital in Dublin in 2024. Gene therapies, however, remain very expensive and the Royal Victoria Eye and Ear Hospital treatment, which was paid for by the Health Service Executive, cost close to €800,000. Dr Duignan says it took years for the team to get the funding in place, but such treatments now mean that Dublin will have two potential centres for gene therapy clinical trials. 'Clinical trials of gene therapies for inherited eye conditions are desperately needed for the treatment of an estimated 5,000 patients on the island of Ireland affected by these diseases,' says Dr Duignan. Drugs used in clinical trials are made available free of charge. Manipulating human DNA – the genetic material responsible for life – is like the stuff of science fiction. How is it even possible? Research into gene therapy goes back to the 1940s and 1950s. The first studies began to recognise that DNA was a transforming substance capable of changing the living characteristics of individuals through a biochemical process. Later, studies identified that human stem cells (mainly found in the bone marrow) could be genetically modified to carry therapeutic DNA which could then differentiate into various cell types to correct genetic defects. In the 1980s, researchers at Boston Children's Hospital published a paper to show a virus could be used to insert genes into blood-forming stem cells. These so-called viral vectors later became an established way to deliver specific genetic material to human cells. In the meantime, the Human Genome Project was completed in 2003, paving the way for gene therapy to become a reality for multiple diseases, especially those caused by mutations in a single gene. What specific diseases are we talking about? The painful and life-threatening sickle cell disease, a rare genetic immune deficiency disorder called chronic granulomatous disease, and the rare childhood disease adrenoleukodystrophy have all been treated with gene therapy. Genetic diseases including cystic fibrosis , muscular dystrophy, sickle-cell anaemia and haemophilia could potentially be treated with gene therapy. But are there risks to making such precise changes to the basic building blocks of life? Yes, there are huge risks, which is why it has taken so long for gene therapy to reach clinical settings. In 1990, four-year-old Ashanthi de Silva became the first patient to be successfully treated with gene therapy. She was given a healthy adenosine deaminase (ADA) enzyme to cure the severe immunodeficiency disorder caused by the absence of ADA. Although she continues to take a drug to keep her condition under control, she leads an active life to this day. [ Delving into the power of DNA for patients Opens in new window ] Throughout the 1990s, European researchers focused on other forms of severe immunodeficiency disorders, reporting the first cures in 2000. However, some years later, five of the 20 treated children developed cancer. The viral vector which had delivered the gene to their T cells (immune cells in the body) had also activated an oncogene, triggering leukaemia. Also in the US, an 18-year-old boy died after receiving gene therapy for a rare metabolic disorder. These incidents delayed research into gene therapy for almost 10 years. But in the early 2010s, scientists developed better viral vectors that could more precisely target expressions of genes in specific cell types which don't go astray in the body and don't trigger an immune response. This spurred further developments in genetic therapies and several gene therapy drugs were approved for use. The use of messenger RNAs (mRNAs) – as was used in Covid-19 vaccines – also represents a form of gene therapy. In this case, the mRNA vaccine introduces information that cells then use to make the coronavirus spike protein, which then stimulates the person's immune system to develop antibodies to the virus. What are the next steps for gene editing and gene therapy? There are now hundreds of active gene therapy studies around the world and more than a dozen gene therapy drugs on the market, according to researchers at Boston Children's Hospital. A more finely tuned approach called base-editing, which uses Crispr technology to chemically change one 'letter' of a gene's code at a time, is deemed to be the next technological advance in genetic therapies. The small changes of base-editing can correct a 'spelling error' mutation, silence a disease-causing gene or help activate a specific gene. However, while this approach hasn't yet been tested in clinical trials, places such as Boston Children's Hospital have several base-editing projects under way. Dr Duignan adds that new so-called gene agnostic therapies, which will treat diseases caused by different gene mutations without having to develop a specific infusion for each mutation, represent the next frontier in gene therapy.
USA Today
17-06-2025
- Health
- USA Today
The trickle-down effect of President Trump's massive NIH budget cuts
The trickle-down effect of President Trump's massive NIH budget cuts U.S. medical research is at a precipice as President Trump proposes cutting $18 billion from the National Institutes of Health. Show Caption Hide Caption Cuts to health research could impact clinical studies and trials at the NIH The Trump administration wants to cut health spending in the coming year, and plans to cut the budget at the National Institutes of Health by $18 billion. Trump administration officials say they are restoring trust in public health and cutting waste. Universities said the Trump administration is marking important studies as Diversity, Equity and Inclusion programs and mistakenly cutting their funding. Fyodor Urnov left the Soviet Union for the United States more than 35 years ago with a dream: To become a scientist and cure rare diseases in the country that was a beacon for biomedical research. Umrov recently was a key member of a team that used gene editing technology to treat a 'stinking cute' New Jersey baby born with a severe disability. That breakthrough, like decades of other medical research he's done, was funded by the National Institutes of Health. But millions of dollars in NIH research has now ground to a halt at universities across the country after the Trump administration cut studies it says are driven by diversity initiatives or a fixation on COVID-19. And the remaining research stands at a precipice as President Donald Trump's budget proposes cutting $18 billion from the NIH next year – the largest cut to any single government agency. NIH grant money doesn't sit in Washington – it gets funneled down to research universities across the country, where professors, graduate students, and doctors do their life's work. The schools include prestigious Ivy League institutions, such as Harvard University, and dozens of lesser-known private and public colleges. 'I really hope that we're going through a focused, phased of review of how funding is distributed,' Urnov said. 'I just cannot imagine a future where American biomedical research is not the shining light that leads the world.' On Jan. 16, a federal judge in Boston said NIH's cancellation of more than $1 billion in research grants on the basis of DEI was illegal and reinstated them. He signaled he could issue a more sweeping decision in the case as it moves forward. But Trump officials say they are restoring trust in public health and cutting waste. 'In recent years, Americans have lost confidence in our increasingly politicized healthcare and research apparatus that has been obsessed with DEI and COVID, which the majority of Americans moved on from years ago,' Kush Desai, a spokesman for the White House, said in a statement. 'The Trump administration is focused on restoring the Gold Standard of Science – not ideological activism … to finally address our chronic disease epidemic.' Texas university loses virus catalog funding The University of Texas Medical Branch in Galveston, which receives about $150 million in NIH grants annually, has already lost $19.3 million, according to Scott Weave, the scientific director for Galveston National Laboratory. Weaver said he's most concerned about the World Reference Center, a collection of thousands of viruses that has been preserved since the 1950s to help scientists conduct emergency research into new viral threats, such as Zika or West Nile virus. In recent years, the research focused on COVID-19. NIH terminated the center's grant funding in full on March 24. In a letter obtained by USA TODAY, the agency wrote: 'These grant funds were issued for a limited purpose: to ameliorate the effects of the pandemic. Now that the pandemic is over, the grant funds are no longer necessary.' Weaver said that framing is incorrect. The project on viruses isn't just focused on COVID-19. Historically, the center worked on mosquito-borne viruses, not respiratory ones. The group only pivoted briefly to help with the pandemic health emergency. He believes the grant was eliminated in error. 'I think it would've been clear if anyone with an understanding of science had read the information about of our grant that we were not a COVID grant,' Weaver said. Research programs mistaken for DEI Andy Johns, who administers research grants at the University of North Carolina at Chapel Hill, described a similar situation. The school lost $7.7 million in NIH contract terminations, which he said began in February but picked up pace in March and April. The cuts include a study on how to improve tobacco regulatory science to reduce health disparities, a study to address COVID-19 vaccine hesitancy in rural communities, a study on neurobiological susceptibility to peer pressure and drug use among teenagers, and a study on malaria in Africa. 'The ones that might sting the most are ones that get caught up because they're perceived as being involving a particular issue that they don't actually involve – where a project may have been deemed as DEI, but there's actually not a DEI focus in any way shape or form,' Johns said. Sometimes, only a small portion of a research project involves analyzing how research affects a specific demographic, experts said, but this has been enough for the Trump administration to flag the grant as DEI. Johns said professors involved in the defunded studies asked NIH to let them continue the underlying scientific research and simply omit the demographic analysis. But the university hasn't haven't seen much success with this approach, he said. Weaver, the Texas researcher, mentioned a grant that helped students who graduated from small colleges that lack research opportunities get research experience before applying to PhD programs. He said NIH cut that on the grounds it was a DEI initiative. Weaver said that while the grant may have technically fit into that category, it was 'more opportunity-based.' He lamented what stripping the campus of the program means: 'I've really taken a lot of pleasure in seeing them succeed and go on and thrive as scientists.' Layoffs in Maryland and California Daniel Mullins, a health outcomes professor at the University of Maryland, Baltimore, said he laid off off five people and reduced the workload of a sixth worker after NIH told them to stop work on a five-year, $9.4 million grant for a health care study. The grant helped Mullins study how to make patients more likely to participate in clinical trials − a vital step in the approval of new medicines. He describes the program as a 'health equity hub,' but says there's no one disease or demographic of people it is specifically designed to help. Mullins' biggest challenge has been walking into work every day and seeing people who are about to lose their jobs. 'I asked the department chair and the dean if we could just fund these people a little bit so they could at least find a job,' he said. Kim Elaine Barrett, the vice dean of research at the University of California Davis School of Medicine, said her school lost grants aimed at building a biomedical workforce that is more representative of the population. Other terminated grants provided stipends and salaries for graduate students and junior faculty. Barrett said the school historically received just over $200 million a year from the National Institutes of Health. She said the funding loss affects about 100 people. "If the situation continues for much longer, and/or gets worse, then we will have to start looking at layoffs, and not just for trainees, but for lab personnel in general," Barrett said. "A lot of faculty derive some or all of their salaries from research grants." 'I wish we had better medications' At Northwestern University, just outside of Chicago, Dr. Benjamin Singer, the vice chair for research in the Department of Medicine, said the university has been 'very gracious' in helping his research group fill in the funding gaps to keep his research group's work going. Singer treats patients in the intensive care unit, and some of his research focuses on how a specific cell can help rebuild a damaged lung – research that can benefit people suffering from pneumonia. His group also identifies targets for potential future prescription drugs. 'I take care of critically ill patients at a high risk of dying,' Singer said. 'When they're really up against a tough spot, I think, 'I wish we had better medications. I wish we had better therapies to help your mom, your son, your daughter.'' The University of Minnesota, which reported losing 24 NIH grants as of early May, created a program to help researchers continue their work if their funding was terminated or they received a stop-work order from the federal government. 'I just can't be clear enough, however," said Rebecca Cunningham, the university's president. "There is no mitigation for the loss of federal funding.' Contributing: Reuters
