Tag: United Kingdom

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Sperm donors need limits, says a European fertility group

Ties van der Meer doesn’t know how many siblings he has.

The 47-year-old was conceived at a private fertility clinic in the Netherlands using sperm provided by an anonymous donor. After the Netherlands banned anonymous donation in 2004, the doctor who ran the clinic destroyed records that might have identified those donors, he says.

He describes the situation as “problematic.” Children have a right to know their biological parents, he says. While he did ultimately track down one sibling, who helped him identify his father along with other genetic relatives, he may have others he’ll never find.

Other donor-conceived people who have been able to track down siblings have found they have tens or even hundreds of them. One donor-conceived woman who found 25 half-siblings over the course of seven years told the Guardian, “It does make you feel a bit mass-produced.”

We need international limits on the number of children a single donor can contribute to, a European fertility organization argued yesterday. At a conference in London, members laid out plans to start with a Europe-wide limit.

Today many countries, including the UK, have banned anonymous egg and sperm donation. But anonymity can’t be guaranteed even in places where it is technically allowed. Genetic tests offered by companies like Ancestry and 23andMe, along with genetic registries, have made it much easier for donor-conceived people to find parents and siblings who share their genes.

And because sperm can be frozen and stored for years before it is eventually used, the current set-up can result in situations where donor-conceived people discover the identity of a genetic parent only after the person’s death. They might also find that they have siblings of very different ages, all around the world.

Some people are finding hundreds of siblings. Sperm from Jonathan Meijer, a Dutch man who began donating in 2007, was used to conceive between 550 and 600 children. (Stichting Donorkind, a foundation and advocacy group for donor-conceived people that’s chaired by van der Meer, took him to court, and he was ordered to stop donating in 2023.)

Stories like these can be distressing for donor-conceived people. And there are other reasons why limits are considered important. The offspring of a prolific donor might be at risk of unknowingly forming romantic or sexual relationships, for instance. And some people are concerned that a donor with a harmful genetic mutation might pass that down to many children.

This is unlikely, given the level of screening that most donors undergo. But it has happened. A man who donated his sperm to a sperm bank in Denmark was found to have a genetic mutation that significantly increased the risk of multiple cancers. But his sperm had already been used to conceive at least 197 children across Europe. Some of those children developed cancer. Some died.

Many countries already have legal limits for donors. In Malta and Cyprus, for example, both egg and sperm donors are allowed to contribute to the birth of just a single child, according to data presented at the European Society of Human Reproduction and Embryology (ESHRE) meeting in London on July 8.

Other countries set limits based on the number of families a single donor can contribute to, allowing recipients to have children who share a genetic link. In the UK, that limit is set at 10 families per donor.

But these limits are difficult to enforce, partly because donated gametes don’t necessarily stay in their original country. In Denmark, the national limit is set at 12 families. But the country is a major exporter of sperm. In the UK, for example, more than half of sperm donations in 2020 were imported—with most of those coming from either Denmark or the US.

“The only thing that really makes sense is a transnational limit,” Jackson Kirkman-Brown, a professor of reproductive biology at the University of Birmingham, said at the meeting.

Kirkman-Brown and his colleagues have spent months putting together a document that represents ESHRE’s position on these limits. After consulting with fertility specialists, clinics, sperm and egg banks, donors, and donor-conceived people, the team has developed a plan to start with a Europe-wide limit on sperm and egg donations.

ESHRE is calling on sperm and egg banks, as well as fertility clinics, to respect an initial limit of 50 families per donor. That’s still very high, according to a handful of people I spoke to at the meeting. But at least it’s a start.

Europe should move toward setting limits at 15 families per donor, Kirkman-Brown said. “We may find that 15 is also too high,” says Vasanti Jadva, who studies the psychological well-being of people conceived using donated eggs, sperm, and embryos at City St George’s in London. “We still don’t know what the right number is.”

It will be difficult to enforce these limits, too. And if they end up limiting the supply of donor sperm, there’s a chance that some people will turn to unregulated sperm donations from people who do not undergo health screening. Unregulated donations can lead to other problems for prospective parents, including the possibility that donors will seek parental rights over the children conceived using their sperm.

And it will be even harder to establish international limits. When I asked the American Society of Reproductive Medicine for its thoughts on ESHRE’s proposed limits, a representative directed me to a guidance document saying “it has been suggested” that for a population of 800,000, single donors should be limited to “no more than 25 births” in order to avoid the risk that relatives will have children together. (Considering the US has a population of over 340 million, the total figure could be pretty high, but many sperm banks opt to limit the number of families contributed to by a single donor at around 25.)

van der Meer thinks that even a limit of five families from a single donor would be high. International donation makes it even harder for donor-conceived people to connect with genetic relatives, so the limit for international contributions should be set at two families, he says.

Still, he thinks ESHRE’s suggested limit is a “positive first step.” Van der Meer has managed to track down a sibling, his father, and nephews, aunts, and uncles. He hopes that future policies respect the rights of donor-conceived children to know, and be in contact with, their genetic relatives.

“But,” he says, “you have to start somewhere.”

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

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Stem Cell Therapy Shows Promise in First Human Parkinson’s Disease Trial

A landmark Phase I/II clinical study led by researchers at Skåne University Hospital and Lund University has shown that transplanting stem-cell-derived dopamine progenitor cells into the brain is feasible. Eight patients with Parkinson’s disease (PD) received transplants of STEM-PD, a cryopreserved, off-the-shelf dopaminergic progenitor product derived from human pluripotent stem cells. The three-year Phase I/II, open-label, multicenter, single-arm, dose-escalation study identified no serious side effects linked to the transplanted cells during the first year of follow‑up.

“The possibility of replacing dopamine neurons that are lost in Parkinson’s disease has been a long-standing goal in the field,” said Malin Parmar, professor of cellular neuroscience at Lund University, and lead of the STEM-PD program. “The findings represent an important milestone for regenerative medicine approaches in Parkinson’s disease and support continued clinical development of stem cell-based therapies.”

Results from the study were reported by Parmar and colleagues in Nature Medicine. In their paper, titled “Human embryonic stem cell-derived dopaminergic cells for Parkinson’s disease: a Phase I/II open-label trial,” the team wrote, “In conclusion, particularly in the context of other recently published trials using human PS cell-derived dopaminergic cell therapies for PD, these findings further support the continued development of this therapeutic approach, including evaluation of the STEM-PD product in larger patient cohorts.”

Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, the authors wrote. In Parkinson’s disease, patients lose nerve cells in the brain that produce dopamine, which leads to symptoms such as slowness of movement, stiffness, gait disturbance, and tremor. “The hallmark pathology of PD involves progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the subsequent loss of their projections to the striatum,” the team explained. Current treatments are medications that replace the lost dopamine, but over time these medications often become less effective and cause side effects.

“Intracerebral transplantation of stem cell-derived dopaminergic progenitors to replace lost endogenous dopaminergic neurons offers a new potentially restorative therapeutic approach for PD,” the investigators continued. Scientists have been working to develop standardized and scalable dopamine cell therapy products derived from pluripotent stem (PS) cells, including human embryonic stem (ES) cells and induced PS (iPS) cells, they noted. “Several such products are now in clinical development … with early safety and feasibility data emerging.”

The transplanted stem cell-based dopamine nerve cell product tested in the newly reported trial is designed to replace the cells that produce dopamine, and the goal is that after being transplanted, the transplanted cells will mature into new dopamine-producing nerve cells in the brain. The STEM-PD trial aimed to evaluate the safety, tolerability, and feasibility of intraputaminal transplantation of STEM-PD in patients with moderately advanced PD.

Eight individuals with Parkinson’s disease received the transplanted cell product at two different doses, followed by 12 months of immunosuppression to prevent graft rejection. All patients were treated at Skåne University Hospital. Seven participants completed 12-month follow-up, and one participant died from a pulmonary infection that was not directly related to the cell product.

The surgical procedure was generally well tolerated, and no graft-induced involuntary movements were observed in the transplanted participants. Clinically, patients remained stable. Imaging using dopamine PET scans provided early indications of graft survival at both 6 and 12 months post-transplantation. Six of the seven participants substantially reduced their dopaminergic medication, a result that will be evaluated over time. In their paper, the team wrote in summary, “This Phase I/II clinical trial involving the bilateral intraputaminal transplantation of the STEM-PD dopaminergic progenitor cell product demonstrates its feasibility with no unexpected safety concerns from the cell product.”

Roger Barker, MD, professor of clinical neuroscience at the University of Cambridge, clinical lead of STEM-PD and clinical PI at the U.K. site, said: “This represents an exciting new departure on repairing the brain of individuals with Parkinson’s using dopamine cells- an approach pioneered in Lund some 40 years ago using fetal dopamine cells. The STEM-PD trial harnessing the expertise of scientists and clinicians from Lund and Cambridge has enabled us to undertake and deliver on one of the first ever stem cell-derived dopamine cell therapies for patients with Parkinson’s, and we hope this will be the beginning of an exciting new programme that may ultimately benefit the wider Parkinson’s community.”

Gesine Paul-Visse, MD, professor in neuropsychiatric research and lead PI at Skåne University Hospital, said, “Reaching this primary endpoint and being able to show that the cell product is safe is a great achievement for this trial, our team, the participating patients, but also for all patients suffering from Parkinson’s disease. We are hopeful that the early signs of cell survival and clinical improvement we observe will continue to increase over time and are excited to continue the development of this cell therapy.”

The STEM-PD research team will now continue the long-term follow-up of the participants to further evaluate safety, graft function, and clinical benefit. “Secondary and exploratory outcomes will evaluate the course and efficacy of clinical features, the survival of grafted dopaminergic cells at 36 months as well as additional safety signals occurring between 12 and 36 months and any dose–response effects,” the investigators stated. “Further evaluation of the grafts up to 36 months will determine whether the implanted cells continue to grow, mature and reinnervate the putamen after 12 months.”

STEM-PD builds on decades of research in dopamine cell replacement therapy for PD at Lund University and pioneering work in translation of pluripotent stem cell technology from experimental studies into clinical evaluation. The STEM-PD trial is the first pluripotent stem cell trial approved in Sweden and the first for PD in Europe. “The initiation and execution of this clinical trial have only been possible through close collaboration between scientists, clinicians, GMP manufacturing teams, regulatory experts and, most importantly, the participating patients,” concluded Parmar. In their report, the authors stated, “The STEM-PD trial adds further important confirmatory and complementary evidence to the recently reported feasibility and short-term safety of PS cell-derived dopaminergic progenitor transplantation in PD.”

The academic Phase I/IIa trial was conducted in collaboration with Novo Nordisk. Cellular Intelligence, a Boston-based company, recently acquired the STEM-PD program and will lead its next phase of clinical development, including a planned Phase II trial. The STEM-PD cells and their continued development hold IND clearance with FDA Fast Track Designation, and Cellular Intelligence aims to advance the program through Phase III to market approval.

STEM-PD is an academic European clinical translation initiative, focused on developing stem cell-based therapies for Parkinson’s disease. The program is led from Lund University with partners from Skåne University Hospital, Cambridge University Hospital, and University College London and combines expertise in stem cell biology, GMP manufacturing, neurosurgery, clinical neurology, and regenerative medicine to advance pluripotent stem cell-derived dopamine neuron therapies toward clinical application.

The post Stem Cell Therapy Shows Promise in First Human Parkinson’s Disease Trial appeared first on GEN – Genetic Engineering and Biotechnology News.

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RecoverEsupport—A Digital Health Intervention for Recovery After Breast Cancer Surgery: Feasibility and Acceptability Outcomes from a Pilot Randomized Controlled Trial

Background: Optimizing recovery following breast cancer surgery is critical for restoring usual function, minimizing complications, and enabling timely initiation of adjuvant therapies. Enhanced Recovery After Surgery protocols are internationally endorsed recommendations and include patient-led behaviors such as early mobilization, early oral intake of fluids and food, postoperative rehabilitation exercises, and multimodal pain management. However, adherence to these behaviors is often suboptimal, and strategies to support patients are limited. Digital health interventions (DHIs) may offer scalable solutions. Objective: The aim of the study is to assess the acceptability of the RecoverEsupport Breast DHI, designed to increase adherence to patient-led Enhanced Recovery After Surgery recommendations across the perioperative period for breast cancer surgery, and to assess the feasibility of conducting a randomized controlled trial to evaluate it. Methods: In this single-site, 2-arm randomized pilot trial, conducted at a major cancer hospital in New South Wales, Australia, between July 2024 and October 2025, participants were consecutively recruited from the surgical list at the study site, supplemented by referrals from surgeons’ private rooms, and included individuals having a mastectomy with or without implant-based reconstruction. Participants were allocated to usual care (control) or usual care plus the RecoverEsupport DHI (intervention). Trial feasibility outcomes included participant recruitment, retention, data completeness, and postoperative safety (adverse events). Intervention acceptability was assessed via the System Usability Scale, participant engagement rates, and willingness to recommend the intervention to others undergoing surgery. Descriptive analyses were conducted, and outcomes were compared to prespecified targets and progression criteria. Results: In total, 23 participants were recruited (control: n=12, intervention: n=11), which was below the target of 70, while participant retention and data completeness were 100% (23/23), both exceeding the targets. No grade 3+ adverse events occurred; minor grade 2 events occurred in both groups. Acceptability outcomes exceeded targets: usability was high (mean System Usability Scale score 83.2, SD 17.7; target >68), 100% (11/11; target >75%) of participants logged in to the DHI at least once, and 88% (10/11; target >75%) would recommend the program to others undergoing surgery. According to prespecified progression criteria, 3 of 4 feasibility targets were met, indicating that a revised recruitment strategy would be required before proceeding. The restrictive eligibility criteria may have contributed to the lower than expected recruitment rate. All 3 acceptability targets were met. Conclusions: The RecoverEsupport intervention was acceptable and safe and had high participant engagement. The trial processes were feasible; however, recruitment barriers, including restrictive eligibility criteria, highlight the need for more robust and integrated recruitment strategies to enable progression to a fully powered randomized controlled trial. Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12624000417583; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386404 International Registered Report Identifier (IRRID): RR2-10.1136/bmjopen-2024-093869
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STAT+: 931 days. The drug approval scandal hiding in plain sight

This story first appeared in Adam’s Biotech Scorecard, a subscriber-only newsletter. STAT+ subscribers can sign up here to get it delivered to their inbox.

Northwest Biotherapeutics, a public biotech company developing a treatment for brain cancer, submitted a marketing application to U.K. regulators in late December 2023. The review was supposed to take 150 days, under an expedited regulatory pathway for drugs that address serious unmet medical needs.

As you’re reading this newsletter, two years, six months, and 18 days have elapsed without an approval decision. Why the extra-long delay? Regulators at the U.K’s Medicines and Healthcare products Regulatory Agency, or MHRA, won’t comment, telling anyone who inquires, including me, that it’s up to Northwest Bio to provide an update on its brain cancer treatment, called DCVax.

Continue to STAT+ to read the full story…

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STAT+: AstraZeneca, Ionis report major trial failure with heart disease drug

LONDON — In a blow to its cardiovascular aspirations, AstraZeneca said Thursday that its drug for a heart disease — one that has become an increasingly competitive target for biopharma companies — failed in a pivotal trial.

The drug, called Wainua, on which AstraZeneca is partnered with Ionis Pharmaceuticals, did not outperform placebo in reducing cardiovascular death and clinical events for patients with a condition known as ATTR-CM, or transthyretin-mediated amyloid cardiomyopathy. 

AstraZeneca’s U.S. shares were down some 8% in premarket trading, while its London-listed shares were down 9% early Thursday. Ionis shares, meanwhile, were down 12% in premarket hours.

Continue to STAT+ to read the full story…

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Non-Invasive Brush Biopsy Test Detects Cancer Within an Hour

In the largest of its kind, involving over 1000 samples from 545 patients, a non-invasive, brush biopsy test detected oral cancer within one hour in a validation test. It is hoped the test will greatly advance oral cancer detection and prevent perhaps over 90% of unnecessary harmful scalpel biopsy procedures, which can be difficult to carry out and may damage underlying tooth and bone structure. 

“We were genuinely astonished by the fact that the brush swab test performance is comparable to a microbiopsy,” said lead author Muy-Teck Teh, PhD. “It suggests that the biological signal captured by these four genes is sufficiently strong and consistent that it can be detected even from the superficial exfoliated cells collected by a brush biopsy.”

The work was published in the Nature journal Biomarker Research by a cross-University team led by Queen Mary University of London researchers. Teh is a professor of molecular oral oncology at Queen Mary of The Centre for Oral Immunobiology & Regenerative Medicine, Institute of Dentistry, Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

Oral cancer is a growing global killer. According to Global Burden of Disease data, lip and oral cancer is among the world’s most rapidly increasing causes of early death. Over ten thousand people in the U.K. were diagnosed with oral cancer last year, according to the charity Mouth Cancer, and 3637 people lost their lives. Almost 650,000 people in America are estimated to get the disease each year and more than 13,000 die from it. Worldwide, it affects 650,000 a year. Risk factors include tobacco use/smoking, alcohol, infection with the HPV virus, and sun damage. Unfortunately, more than half (53%) of all mouth cancers are diagnosed in stage IV, where the cancer is at its most advanced.

Cases Human of Papillomavirus (HPV)—specifically HPV type 16 is thought to cause a large proportion of this disease. While the HPV vaccine is having tremendous effect protecting young girls and women from HPV-related cervical cancer, there has been less pick-up of the vaccine among boys.

Oral squamous cell carcinoma (OSCCs) are usually diagnosed early using scalpel biopsies. Early diagnosis is critical for the greatest chance of survival, yet most oral potentially malignant disorders (OPMDs) are benign, and patients frequently undergo unnecessary invasive scalpel biopsies, creating diagnostic delays and harms. A scalpel oral biopsy can be extremely painful—especially the tongue (the most common cancer site)—essentially because part of the tongue is removed. But the overwhelming likelihood is that the growth is benign.”

These circumstances discourage both patients and clinicians from doing biopsies repeatedly and in a timely fashion. This study aimed to find out if a successful microbiopsy-based multigene assay (qMIDS-V2) could be adapted into a rapid, non-invasive brush biopsy test (qMIDS-V3) for accurate OSCC detection. This new test could potentially spare over 90% of low-risk OPMD patients from unnecessary invasive tissue biopsies. 

The prospective diagnostic case-control study validated a multigene mRNA test (qMIDSV3) for OSCC detection using 1090 oral brush biopsies from 545 patients. Each patient provided paired brush biopsies from oral lesion and contralateral non-lesion mucosa, including OSCC (n = 443), oral leukoplakia (OL; n = 63), and oral lichen planus (OLP; n = 39). qPCR quantified mRNA levels of four genes (INHBA, S100A16, YAP1, POLR2A) from each brush biopsy, and an algorithm generated a malignancy index for cancer risk stratification.

qMIDSV3 distinguished OSCC from OL and OLP with AUC 0.975, sensitivity 95.7%, specificity 95.1%, and overall accuracy 95.5%. False-positive and false-negative rates were 4.9% and 4.3%, showing the test has high specificity for detecting malignant cells rather than premalignant or inflammatory lesions.

The test could thus give clinicians a rapid, accurate, and non-invasive way to triage patients. It can also be repeatedly administered. “That means doctors can now monitor patients with persistent pre-malignant lesions regularly and systematically—and pick up cancers much earlier than we would have been able to before,” said Teh.

Overtesting is also a problem. In the U.K., a current 10 year audit reported a 450% rise in two week wait referrals alongside a 50% drop in cancer detection rate. Subsequent audits showed that 92.5–99.5% of referred patients were cancer free, with most (96–98%) remaining cancer free at 5-year follow up. This latest study builds on substantial of prior clinical validation. 

The team included researchers from Queen Mary University of London’s Centre for Oral Immunobiology & Regenerative Medicine, King George’s Medical University in India, Modern Dental College & Research Centre in India, and the All India Institute of Medical Sciences.

 

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