Research led by University College London has characterized a specific gut microbiome signature found in people with Parkinson’s disease.
Writing in Nature Medicine, the researchers also found that people carrying a genetic mutation in the GBA1 gene that put them at risk of developing Parkinson’s disease had gut microbiomes similar to people with the condition.
Parkinson’s is the second most common neurodegenerative disease in the U.S. after Alzheimer’s disease affecting more than one million people across the country. By the time full-blown motor symptoms emerge, a large degree of neurological damage has already occurred, so much work is underway to find ways to predict and diagnose early disease, as well as to develop more effective treatments.
“In recent years there has been a growing recognition of the links between Parkinson’s disease—a brain disorder—and gut health,” said co-lead author Anthony Schapira, MD, a professor at UCL Queen Square Institute of Neurology, in a press statement.
“Here we have strengthened that evidence and shown that microbes in the gut can reveal signs of Parkinson’s and may be an early warning signal… years before symptom onset.”
For this study, the researchers evaluated gut microbiome samples from 271 Parkinson’s disease patients, 43 people carrying GBA1 risk variants who did not yet have disease symptoms and 150 healthy controls. They also validated their findings in a further 638 people with Parkinson’s and 319 healthy controls from the U.K., Korea, and Turkey.
Schapira and team used DNA sequencing to see which bacterial species were present in each person’s gut. Comparing people with Parkinson’s disease to healthy controls, they found 176 bacterial species that were more or less common in people with the condition.
For example, people with Parkinson’s had more potentially pro‑inflammatory bacteria, including Bifidobacterium longum and B. dentium, Streptococcus mutans, and Lactobacillus paragasseri, than healthy controls.
In contrast, healthy controls had more helpful, butyrate‑producing gut bacteria from including Roseburia intestinalis, R. inulinivorans and some Faecalibacterium species and less pro-inflammatory species.
Notably, people in the at-risk group who carried a GBA1 risk variant had a gut microbiome somewhere between healthy controls and people with Parkinson’s, suggesting that the composition of microbes in the gut may change over time as the disease develops. In this group, 142 of the 176 species that differed in people with Parkinson’s versus healthy controls also showed changed abundance.
“For the first time we identify bacteria in the gut of people with Parkinson’s that can also be found in those with a genetic risk for the disease, but before they develop symptoms. Importantly, these same changes can be found in a small proportion of the general population that may put them at increased risk for Parkinson’s,” said Schapira.
“This discovery opens the way not only to see if the bacteria are a way to identify those at risk of Parkinson’s, but also to see if changing the bacterial population, through dietary changes or medication, can reduce a person’s risk for Parkinson’s.”
SAN DIEGO, CA – In 1977, when David R. Parkinson, MD, graduated from medical school at the University of Toronto and moved to McGill University to train in internal medicine and eventually hematology, the idea of medical oncology was in its infancy. In Canada, the profession didn’t exist.
“In Canada, there were no medical oncologists,” Parkinson told Inside Precision Medicine. “Radiation therapists administered what little chemotherapy existed. They resisted the development of medical oncology as a specialty.”
David R. Parkinson, MD, recipient of the 2026 AACR Outstanding Achievement Award for Service to Cancer Science and Medicine [The American Association for Cancer Research (AACR)]
Through the ensuing 49 years, Parkinson didn’t just see the rise of kinase inhibitors, antibodies, and cell therapies in real-time—he helped create the world of modern cancer therapeutics.
In reflecting on his remarkable career, which was recognized with the 2026 AACR Outstanding Achievement Award for Service to Cancer Science and Medicine, Parkinson said, “I’ve essentially grown alongside the field.”
From scarcity to structure: Oncology’s early years
When Parkinson arrived in Montreal, there were only a handful of chemotherapeutics available. “In those days, there were only one or two drugs available for hematologic malignancies across the entire field,” Parkinson said. “The main treatments were cyclophosphamide and nitrosoureas.”
Even supportive care lagged. “Initially, we had no effective way to control chemotherapy-induced nausea,” he noted of the standard of care for testicular cancer. “Some patients stopped treatment because they couldn’t tolerate it.”
Parkinson explained that early cancer drugs worked best on rapidly dividing tumors, like leukemias and testicular cancers, because that’s what the animal models represented. These therapies targeted DNA and cell division broadly, often with severe toxicity, and were far less effective against slower-growing solid tumors.
After his residency at McGill, Parkinson moved to Boston, first to Tufts New England Medical Center on a modest Canadian fellowship that placed him at the edge of a field just beginning to coalesce. “I was on a Canadian fellowship earning $12,000 a year,” he said. “The exchange rate fluctuated significantly, which made things difficult, and I couldn’t work due to my student visa.”
What he found, however, was momentum. Through connections with Dana-Farber, Parkinson entered formal training in medical oncology as the specialty began to take shape. “I connected with Dana-Farber and took their introductory course for fellows—that was my entry into medical oncology.”
At the same time, breakthroughs in specific cancers hinted at what might be possible. “What really shaped my thinking was the emergence of treatments for testicular cancer just as I entered oncology,” he said. “Platinum-based therapies—and later combination regimens—felt like miracles. We had never seen anything like it. These were often young patients, difficult to manage, but suddenly there were real cures.”
Targeted therapy and the Gleevec moment
Parkinson’s career soon intersected with early efforts to harness the immune system against cancer—decades before immunotherapy became a dominant paradigm. “I became deeply involved in immunotherapy, particularly interleukin-2 and early tumor-infiltrating lymphocyte studies,” he said.
Working at the National Cancer Institute (NCI), he collaborated with leaders, including immunotherapy pioneer Steven Rosenberg, MD, PhD, maintaining a hybrid role that combined research with clinical care. “At the same time, I continued clinical work for a couple of months each year, collaborating with Steve Rosenberg in the surgical branch.”
These early approaches were technically challenging and often unpredictable, but they laid the groundwork for later advances. “We started with basic approaches, moved to tumor-infiltrating lymphocytes, and eventually to engineered CAR T cells,” Parkinson said. “Progress has been steady, though often slower than those treating patients would like.”
If immunotherapy represented one trajectory, targeted therapy represented another—one that depended on a deeper understanding of cancer biology.
“When I joined Novartis in the late 1980s, we were among the first developing kinase inhibitors,” Parkinson said. At the time, the idea was controversial. “Early skepticism suggested kinase inhibitors wouldn’t work due to high intracellular ATP levels and structural challenges.”
But advances in molecular biology were beginning to change the landscape. The discovery of the Philadelphia chromosome and its associated oncogene created a clear therapeutic target. “The Philadelphia chromosome had been known since the 1960s, and by the 1980s the responsible gene was identified,” Parkinson explained.
The result was imatinib (Gleevec), a drug that would become a prototype for precision oncology. “Eventually, a small molecule inhibitor was developed that targeted it precisely.”
The clinical results were extraordinary. “By the third cohort in a Phase I trial, patients with chronic myelogenous leukemia showed dramatic responses—some within 24 hours,” Parkinson said. “It’s probably the only Phase I oncology trial where essentially every patient achieved remission.”
For Parkinson, the implications extended far beyond a single drug. “Of course, [Gleevec] was a unique case,” he said. “But it proved an important point: what once seemed impossible can become possible.”
Since then, the field has expanded dramatically. Hundreds of kinase inhibitors have been developed, with thousands more explored, reflecting a broader shift toward therapies grounded in specific molecular mechanisms.
Precision medicine—and its limits
As oncology evolved, so too did its language. “For years, we called it ‘personalized medicine,’” Parkinson said. “I used to joke that medicine has always been personalized—you’re always trying to determine what’s best for a specific patient in a specific context.”
He credits industry with popularizing a more precise term. “Although Pfizer popularized the term ‘precision medicine,’ I think it’s a better term,” he added, with a note of humor: “I have a few good Pfizer jokes—best shared over a drink.”
Yet the reality of precision medicine has proven more complex than its promise. “The evolution of therapeutics mirrored the models and biological understanding available,” Parkinson said. “Targeted therapies only emerged once we understood the biology. Diagnostics, however, lagged by about two decades.”
That lag remains a structural challenge. Parkinson founded a diagnostics company based on single-cell signaling technology developed at Stanford. “Technically, it worked—we solved major challenges in instrumentation, standardization, and analysis,” he said. “But we couldn’t establish a viable business model.”
The core issue was reimbursement. “Without adequate reimbursement from Medicare, even highly sophisticated diagnostics struggle commercially,” said Parkinson. “Better diagnostics can reduce the use of expensive drugs by identifying who won’t benefit—something that doesn’t always align with pharmaceutical business models.”
In recent years, Parkinson has focused increasingly on large-scale data integration, including his involvement with the GENIE consortium. The initiative aggregates genomic and clinical data across institutions, aiming to accelerate discovery and improve clinical decision-making. “GENIE has been a technical success,” he said. “But its long-term sustainability remains uncertain.”
The broader challenge, he argues, is conceptual as much as technical. “Looking forward, the field is evolving toward integrating multiple data types—genomics, transcriptomics, imaging, and more—to better understand tumor biology,” he said. “Sequencing alone isn’t enough. The challenge now is not a lack of data, but making sense of it—something where artificial intelligence will play an increasingly important role.”
Back to basics
Across academia, government, and industry—including roles at the NCI, Novartis, Amgen, and Biogen Idec—Parkinson sees a single throughline. “I remember an interview with a biotech company where an HR representative told me, ‘You seem to have done a lot of different things,’” he said. “I responded that I had really only done one thing: trying to improve cancer treatment, just from many different angles.”
Not every effort succeeded. “In one case, we developed a drug that performed beautifully in mice but failed in human trials,” he said. “That’s common in oncology—most ideas don’t translate. You don’t think of it as failure but as learning. Still, there’s a limit to how many ‘learnings’ one can appreciate.”
Reflecting on decades of progress, Parkinson emphasizes both how far the field has come and how much remains unresolved. “Outcomes have improved dramatically across several cancers, especially hematologic ones,” he said.
Yet he underscores a fundamental principle: that progress in cancer treatment comes down to understanding biology. “The better we understand it, the more effectively we can develop targeted therapies,” said Parkinson. “Without that understanding, we’re essentially guessing.”
At AACR 2026, Parkinson’s recognition underscores not just past achievements but a continuing trajectory—one shaped by the interplay of discovery, failure, and persistence. “Despite all the challenges,” he said, “[precision medicine] is still the most promising path forward.”
Results from a large U.K. study show that vaccination against respiratory syncytial virus (RSV) at least two weeks before giving birth has a significant protective effect against hospitalization for this infection in babies born to these mothers.
As reported at the congress of the European Society of Clinical Microbiology and Infectious Diseases in Munich this week, the researchers found that vaccination reduced a baby’s risk of being admitted to hospital with serious RSV lung infections in the first months of life by around 80% versus no vaccination.
Notably, the benefit from vaccination increased if mothers were vaccinated at least four weeks before the baby was born, although even if they received the vaccine 10-13 days before delivery the risk of hospitalization for their babies in subsequent months still went down by 50%.
“As the largest study to date examining the impact of this vaccine on infant hospitalization, these findings provide robust evidence that vaccination offers substantial protection against severe illness in young infants,” commented lead author and UK Health Security Agency epidemiologist Matt Wilson in a press statement.
“We found a clear relationship between timing and protection, with effectiveness increasing as the interval between vaccination and birth lengthens, reaching close to 85% when vaccination occurs at least four weeks before delivery.”
After a national RSV vaccination campaign for pregnant women began in the U.K. in September 2024, around 55% coverage was reached by December of the same year. In total, 289,399 infants born between September 2024 and March 2025 were included in the cohort of which around 55% were vaccinated via maternal exposure. Vaccination was considered ‘full’ if mothers received it at least 14 days before giving birth.
The team followed up the babies for around three months after birth to monitor for RSV-associated lower respiratory tract infections requiring hospitalization, which affected a total of 4,594 babies.
Overall, unvaccinated babies had around seven times the rate of RSV‑related hospital admissions compared with babies whose mothers were vaccinated during pregnancy. Preterm infants also benefitted significantly from the vaccine.
“These findings are particularly important for preterm infants, who are among the most vulnerable to severe RSV infection,” said Wilson. “With sufficient time between vaccination and birth, we saw good levels of protection in these babies. Giving the vaccination early in the third trimester, as recommended by the World Health Organization, could protect most preterm infants.”
Background: Wearable devices enabling remote monitoring by surgeons of their patients have gained prominence around total joint arthroplasty (TJA), offering continuous patient data to identify those not meeting postoperative goals, thereby facilitating timely interventions. While multiple studies highlight the utility of these devices in tracking postoperative progress, a standardized approach to their application is lacking. This review aims to synthesize existing literature on the use of wearable device-tracked activity for monitoring TJA outcomes. Objective: We examined the current literature to evaluate how wearable devices are used in monitoring and improving patient rehabilitation and outcomes following TJA. Methods: A systematic review was conducted following Cochrane methodology. A literature search of all available literature was performed in April 2024 and identified 102 studies to undergo full-text review. Systematic reviews, duplicate papers, and theoretical papers were excluded. Ultimately, 35 studies met the selection criteria. Results: The review revealed that 32 of 35 (91.4%) studies used wearable devices to monitor step counts. A total of 21 (60%) studies incorporated joint-specific patient-reported outcome measures, though the specific measures varied. Further, 9 studies used standardized performance-based outcome measures, which also differed across studies. Finally, 7 (20%) studies collected sleep data; however, the methods and outcomes for sleep measurement were inconsistent among these studies. Conclusions: Remote monitoring via wearable devices offers a novel approach to tracking outcomes in TJA patients. Although the use of these devices in perioperative care is expanding, significant variability exists in the data reported across studies. Wearable monitoring is often integrated with patient-reported outcome measures and standardized functional assessments, yet the optimal data parameters that best correlate with established outcome metrics remain undefined. Additionally, data collected by wearables has not yet been shown to predict patient recovery or satisfaction. Further research is essential to refine these data parameters and the development of postoperative protocols that leverage wearable devices to enhance patient compliance and improve clinical outcomes. Trial Registration: PROSPERO CRD420261346230; https://www.crd.york.ac.uk/PROSPERO/view/CRD420261346230
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The study was led by scientists in the pathology department at the University of Cambridge working alongside collaborators elsewhere. Together, they “developed a gene delivery system to express anti-inflammatory cytokines in the lung, which reestablishes local immune homeostasis without triggering systemic effects,” according to details provided in the paper. Specifically, they used an adeno-associated virus cargo system (AAV6.2-CC10) to induce “production of interleukin-2 (IL-2), IL-1 receptor antagonist (IL-1RA), and IL-10 in situ in the lung microenvironment.” They accomplished this “with no detectable expression or immunological deviation in the peripheral immune system.”
According to the developers, their work could lead to new therapeutics that control inflammation following several viral infections, which has been linked to higher mortality rates in cases of SARS-CoV-2 and influenza. Prolonged inflammation during a viral infection also increases the chances that patients could contract bacterial and fungal infections. Importantly, the approach provides a way to harness the “therapeutic potential of immunomodulatory cytokines” which to date have had limited success as biologic drugs due in part to the short half-lives of cytokines as well as the risks of multiorgan effects. “This tool has been proven to deliver sustained and localized expression as evidenced by the results from three tested cytokines,” the effects of which were “restricted to the lungs” and resulted in “prolonged production over the course of weeks.”
The paper goes into the details of how the scientists characterized their method and demonstrated that it induced expression only in specific lung epithelial cells without off-target accumulation. Also provided are details of how they used the system to assess how lung-specific expression of IL-2, IL-1RA, and IL-10 affected disease severity in mouse models of influenza. They found that IL-2 expression was not especially beneficial during infection, possibly due to the amplification of protective regulatory T cells and proinflammatory CD8 T cells in the lungs. However, IL-1RA and IL-10 reduced tissue damage and improved recovery after infection and inflammation.
In addition, data from their experiments showed that delivering either individual cytokines or a cocktail of all three protected mice from influenza-associated aspergillosis. In fact, treated mice showed “reduced neutrophil infiltrates and improved health outcomes,” including reduced weight loss compared to untreated mice, the scientists wrote.
Future experiments with human cell culture systems could lay the groundwork for preclinical testing. However, there are still some limitations. For example, “we did not evaluate the kinetics of repeated administration of the same AAV vectors,” the scientists wrote. “Repeated administration can lead to the development of neutralizing antibodies, which can hinder the uptake of AAVs in subsequent treatments.” Another challenge is with the cargo itself. Though it performs well in mouse models, its “utility in a patient-based setting needs to be tested,” the scientists said.
For years, patients with HER2-mutant non–small cell lung cancer (NSCLC) have occupied a frustrating gap in precision oncology. While targeted therapies have transformed outcomes for EGFR– and ALK-driven lung cancers, HER2-mutant disease has lagged behind, with chemotherapy remaining the standard first-line option.
New data from the Phase Ia/Ib Beamion LUNG-1 trial, published in The New England Journal of Medicine, suggest that this may be changing. The oral HER2 inhibitor zongertinib demonstrated high response rates and durable clinical benefit in treatment-naïve patients, positioning it as a potential new first-line standard.
A long-standing unmet need
HER2 mutations occur in approximately 2–4% of NSCLC cases and are associated with aggressive disease and poor prognosis. Despite advances in targeted therapy across lung cancer, patients with HER2-driven tumors have historically had limited options, particularly in the first-line setting.
Until recently, treatment largely relied on chemotherapy, with or without immunotherapy, yielding modest outcomes, including progression-free survival typically under seven months.
“Just a few years ago, patients with this disease had no effective targeted therapies,” said John Heymach, MD, PhD, principal investigator of the study. “Now, healthcare providers have a HER2-targeted treatment option that can make a meaningful difference.”
High response rates and durability
In the trial, 74 previously untreated patients with advanced or metastatic HER2-mutant NSCLC received zongertinib at the selected dose of 120 mg daily. The results were striking.
A confirmed objective response was observed in 76% of patients, including both complete and partial responses. Tumor shrinkage was both rapid and durable, with a median duration of response of 15.2 months and median progression-free survival of 14.4 months.
These outcomes represent a substantial improvement over historical benchmarks and suggest that HER2-mutant NSCLC may finally benefit from the kind of targeted therapy success seen in other molecular subtypes.
“We observed unprecedented response rates for this cancer subtype,” Heymach said.
A more selective approach to HER2 targeting
One of the key differentiators of zongertinib is its selectivity. Unlike earlier HER2-targeted approaches, the drug inhibits HER2 while sparing wild-type EGFR, a closely related receptor whose inhibition is often associated with toxicity.
Zongertinib is described as an oral, irreversible tyrosine kinase inhibitor that selectively targets HER2 while minimizing EGFR-related side effects.
Clinically, this translated into a manageable safety profile. Most adverse events were low-grade, with relatively low rates of severe diarrhea and rash, common toxicities associated with EGFR inhibition. Serious complications such as interstitial lung disease were rare.
Activity in brain metastases
HER2-mutant NSCLC is also characterized by a high incidence of brain metastases, a major clinical challenge. Notably, the study demonstrated meaningful activity in this setting as well.
Among patients with active brain metastases, 47% achieved a confirmed intracranial response. Responses were also observed regardless of HER2 mutation subtype or baseline brain involvement, suggesting broad applicability across patient subgroups.
This intracranial activity is particularly significant, given the limited effectiveness of many systemic therapies in the central nervous system.
Implications for first-line treatment
The emergence of zongertinib as a first-line option marks a potential inflection point in the treatment of HER2-mutant NSCLC. For the first time, patients may be able to receive a targeted therapy at diagnosis, rather than progressing through less effective chemotherapy regimens.
The data have already translated into regulatory momentum. Zongertinib recently received accelerated FDA approval for this indication, reflecting both the strength of the clinical data and the unmet need in this population.
However, important questions remain. The current study is single-arm and lacks a direct comparison with standard-of-care therapies. A Phase III trial is ongoing to evaluate zongertinib against chemotherapy-based regimens in the first-line setting.
Positioning within a changing landscape
The broader treatment landscape for HER2-mutant lung cancer is also evolving. Antibody–drug conjugates such as trastuzumab deruxtecan have shown activity in previously treated patients, but are associated with notable toxicities and are typically used after progression.
Zongertinib’s oral administration, favorable safety profile, and first-line efficacy could shift treatment sequencing, potentially moving targeted therapy earlier in the disease course.
At the same time, resistance mechanisms are likely to emerge. Early data suggest that distinct resistance pathways may develop for tyrosine kinase inhibitors compared to antibody-based therapies, raising the possibility of sequential or combination strategies.
Looking ahead
As HER2-targeted therapies move into earlier lines of treatment, the focus will increasingly shift toward optimizing sequencing, managing resistance, and identifying combination approaches.
For now, the results from Beamion LUNG-1 provide strong evidence that HER2-mutant NSCLC, long considered a difficult-to-treat subtype, may finally be entering the era of precision oncology.
With high response rates, durable benefit, and activity in brain metastases, zongertinib offers a compelling new option, and a clear signal that the treatment paradigm for these patients is changing.
Minimal residual disease (MRD) continues to be a central focus at the AACR meeting. The small numbers of cancer cells that remain in the body after treatment helps gauge the effectiveness of a treatment and relapse risk. The ability to detect those cells, even in tiny amounts, is an ongoing goal of the cancer community.
At this year’s AACR, the sequencing company Ultima Genomics is announcing new findings in this area using its ppmSeq technology. The data will be presented across six abstracts, including a plenary session.
Highlighting the program will be initial TRACERx (TRAcking Cancer Evolution through therapy (Rx)) MRD data showcasing performance of ppmSeq relative to ultrasensitive bespoke panels.
TRACERx is a long-term study—one of the largest tumor evolution studies—funded by Cancer Research UK. The program analyzes how cancer evolves, spreads to other parts of the body, and develops resistance to treatments. Instead of taking just one biopsy, researchers sample different parts of the same tumor and metastases; the program involves sequencing multi-region and multi-time-point genetic data from over 3,200 tumor samples from over 800 lung cancer patients.
The data will be presented at a plenary session by Charles Swanton, FRCP, BSc, PhD, professor at The Francis Crick Institute in the U.K. He will present an early validation pilot of ppmSeq across 50 plasma samples—using tumor-specific variants identified from prior whole genome sequencing—achieved high analytical sensitivity for ctDNA detection at low single-digit parts-per-million.
“TRACERx has always followed the science of cancer evolution wherever it leads,” said Swanton. “Improving the sensitivity of ctDNA detection is central to the wider ambition for MRD monitoring, and expanding studies across a broader patient population will give us the statistical power and clinical context to determine how whole genome MRD monitoring can be deployed at NHS scale and beyond.”
Data from collaborators will also be presented at the conference. Labcorp will present data from an independent analytical study of an assay developed in coordination with ppmSeq technology, including the performance across multiple solid tumor types in pre-surgical, treatment-naive plasma samples. This analysis of 120 non-cancerous donor samples showed specificity exceeding 99.9%, underscoring the ability of ppmSeq whole genome sequencing to accurately differentiate between cancerous and non-cancerous samples, minimizing false positives. Additional analysis across three commercially available cancer cell lines spanning 13 concentration levels from 0.5 to 500 parts per million showed a 95% limit of detection below 3 ppm, demonstrating the assay’s capacity to detect ultra-low levels of circulating tumor DNA (ctDNA).
“For a long time, the question has been whether you can get truly ultra-sensitive MRD detection from a whole genome approach without all the complexity of bespoke assays,” notes Gilad Almogy, PhD, CEO of Ultima Genomics. “What these AACR data show is that the answer is yes. We’re seeing ppmSeq deliver the level of sensitivity needed to make whole genome MRD practical, scalable, and much easier to deploy globally.”
