These studies cover a number of important areas, including gene therapy for prion disease, base editing therapy for sickle cell disease, early detection of breast cancer, and novel interventions for autism, indicating that important breakthroughs in the treatment of these diseases and medical technology may occur.
The internationally renowned journal Nature Medicine has published its annual feature article, looking at 11 clinical studies that could have a significant impact on the field of medicine in the coming year.
Here are the 11 clinical studies (in no particular order) :
1. Gene therapy for prion disease
Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are rare.
These diseases are a group of neurological degenerative diseases caused by abnormally folded prion proteins, which can cause normal proteins to misfold as well, forming aggregates in the brain that lead to nerve cell damage and death.
Due to their rarity and serious clinical consequences, the diagnosis and treatment of prion diseases remains a challenge in medical research.
There is currently no effective treatment on the market that can cure the disease.
Thanks to earlier research on prion therapy by Sonia Vallabh, a prion scientist at MIT’s Broad Institute and Harvard University in Cambridge, and others, ION-717, a gene therapy drug for the disease, has entered phase 1/2 clinical trials.
ION-717 is a nucleic acid drug developed by Ionis Pharmaceuticals to inhibit the production of prion proteins.
The drug is administered by intrathecal administration.
This trial is already underway at 16 clinical trial sites around the world.
Sonia Vallabh said the goal of her work is to push the therapy to start treatment earlier in the patient population, because the earlier the intervention, the more effective it is in maintaining brain function.
She expects to see the first data analysis by the end of 2025.
This clinical study is an important milestone for the treatment of prion diseases and has the potential to provide lessons for the early treatment of other neurodegenerative diseases.
2. Research on Precision nutrition in diverse populations
Traditional dietary intervention studies are often conducted only in specific populations and ignore the presence of diversity such as age, gender, and socioeconomic status, so these studies may not fully reflect the different responses of different individuals to the same foods and eating patterns.
To better understand how individuals “respond” to their diets, the National Institutes of Health (NIH) funded the Nutrition for Precision Health project, which partnered with the “All of Us” research initiative, It aims to explore why the body responds differently to the same foods or eating patterns.
The project will study more than 8,000 adults, with few exclusions. Scientists will map out how factors such as a person’s daily diet, genes, microbiome, lifestyle habits, and medical and health history affect how they respond to the “diet test.”
The scientists then used this information to predict how individuals would respond after following three different dietary patterns for two weeks.
The researchers will rely on advanced statistical models and machine learning techniques to first identify the factors or individual characteristics that are most relevant for eating responses, and then predict which foods and eating patterns are most likely to provide people with health benefits.
Preliminary (partial) data analysis results are expected in early 2025, and all data collection is expected to be completed by summer 2026.
If CRISPR is the crown of gene editing, the base editor is the crown jewel. Base editing technology has been named “Top Ten Breakthrough technology of the Year” in Science.
3. Base editing based gene therapy for sickle cell disease
Traditional CRISPR gene editing technology can induce DNA double strand breaks (DSB) by cutting at the target site, and then induce homologous recombination (HR) and non-homologous end join (NHEJ) repair pathways in the cell, so as to realize the editing of genomic DNA at the point of knockout and insertion.
But DSB-induced DNA repair is difficult to achieve single-base mutations.
Unlike first-generation CRISPR editing, which cut two strands of DNA, base editing is like erasing disease-associated individual bases with an eraser and refilling in the therapeutic ones – that is, base editing aims to change a single “letter” of DNA without causing a double-strand break, an approach considered much less risky than double-strand DNA breaks.
At present, base editing technology has made many breakthroughs in in vitro gene therapy and in vivo gene therapy clinical trials.
The BEACON clinical trial launched by Beam Therapeutics, a base-editing therapy company founded by base-editing pioneer David Liu, was designed to evaluate the safety and efficacy of base-edited autologous hematopoietic stem and progenitor cells in patients with severe sickle cell disease.
The drug is the first base editing therapy product to enter the clinic.
Unfortunately, one patient in the trial died from lung damage, a known side effect of using the chemotherapy drug busulfan, Busufathane is one of the standard treatments used to “create an environment in the bone marrow conducive to the survival and proliferation of transplanted cells” before a patient has a bone marrow transplant or stem cell transplant, so the patient’s death was not caused by base editing.
In addition to sickle cell disease, base gene editing therapies are currently being developed to treat a range of conditions such as hereditary blindness, cancer and hereditary hypercholesterolemia.
There is reason to believe that as base editing technology continues to develop, the technology will be applied to more common diseases, such as Alzheimer’s disease.
Aditi Bunker, an epidemiologist at the University of Heidelberg in Germany, led a field trial of “cool roofs” to prevent heat-related diseases.
“Cool Roof” is a highly reflective roof coating that reduces indoor temperature by reflecting solar radiation, preventing heat transfer to the interior of the building.
The technology is easy to implement, inexpensive, and has immediate benefits, making it particularly suitable for living in poorer areas affected by extreme heat, such as West Africa, where heat exposure often leads to multiple cases of illness and even death.
In Burkina Faso, a country in West Africa, Bunker’s team conducted a trial involving 1,200 participants from 600 households in 25 villages.
The trial was recently completed and the data are now being analysed.
The researchers randomly assigned the homes to install cool roofs and tracked multiple health indicators over a two-year period, focusing on heart rate, which is sensitive to heat exposure.
Secondary monitoring indicators include blood pressure, body temperature, blood sugar level and body dehydration.
They also looked at indicators of mental health, sleep quality and violent behavior.
The main goal of the study was to determine whether there was a causal relationship between the “cool roof” intervention and improved human health.
By using both objective measures (such as biomarkers) and subjective measures (such as participants’ experiences), the researchers aim to gain a comprehensive understanding of how heat exposure affects health and the effectiveness of such interventions in mitigating those effects.
The trial will help determine whether these interventions should be scaled up locally.
5. Radiotherapy ligand for prostate cancer
Bunker believes this work has the potential to improve the lives of people in some of the most heat-sensitive areas of the world.
The idea of using Lu-177 (lutetium-177) to target to “kill” cancer cells expressing prostate-specific membrane antigen (PSMA) has been around for more than 15 years, but its effective advance in clinical development only accelerated after Novartis acquired Endocyte, a company specializing in radiolandin therapies.
In 2022, the U.S. Food and Drug Administration (FDA) approved Lu177-PSMAA-617 (trade name Pluvicto) for the treatment of adult patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) who have already received androgen receptor pathway inhibitors and taxan-based chemotherapy.
This approval paves the way for the broader application of Lu-177 therapy to prostate cancer treatment in other conditions.
Oliver Sartor, an oncologist at Mayo Clinic, and Scott Tagawa, an oncologist at Cornell University, designed the PSMAddition trial, which compared Lu177-PSMA-617 combined standard treatment with standard treatment alone.
Effects in 1126 patients with untreated or only lightly treated PSMA positive metastatic hormone-sensitive prostate cancer.
Hormone therapy may alter PSMA expression and radiotherapy sensitivity, which may affect the efficacy of Lu177-PSMA-617.
If Lu177-PSMA-617 is able to obtain FDA approval for patients with hormone-sensitive prostate cancer, it will bring significant hope to thousands of prostate cancer patients worldwide.
Pluvicto’s higher price may limit its availability worldwide.
6. Chatbot AIDS cervical cancer screening
In France’s cervical cancer screening program, women aged 30 to 65 have the option of taking their own human papillomavirus (HPV) samples at home, but studies have shown that fewer than 20 percent of women who have not screened at a clinic participate in the self-sampling program.
To increase the participation of this group of women, especially those with lower levels of education and those from regions with high prevalence of the disease, IARC scientist Farida Selmouni’s team has developed a multilingual decision aid chatbot that provides services to users via smartphone channels. To increase participation in the national cervical cancer screening programme in France.
The results showed that women satisfied with the chatbot, believing it could answer their questions quickly and accurately.
An ongoing randomized controlled trial, expected to completed in 2025, aims to evaluate the effectiveness of chatbots in improving women’s participation in HPV-based cervical cancer screening pathways.
If proven effective, this tool will help increase participation in screening programs, thereby reducing cervical cancer morbidity and mortality.
7. Digital mobile kits address adolescent mental health issues
The Screening and Enhancing Adolescent Lives through the Mobile Health Toolkit (mSELY) study, led by scientist Keng-Yen Huang of the New York University School of Medicine, aims to address mental health issues faced by adolescents in low – and middle-income countries such as Kenya.
The mSELY study will assess the effectiveness of digital toolkits in their use by Kenyan adolescents and their parents.
The version for teens will help them to do self-assessment and meet their mental health management needs, and build positive connections with peers;
The version for parents designed to help parents learn strategies to promote adolescent mental health and provide parents with better parenting knowledge.
The study will conduct a randomized controlled trial in multiple community organizations in Kenya to verify the effects of these digital tool interventions.
8. Individualized breast cancer screening
Current breast cancer screening is primarily based on age, with screening usually starting at age 50 in most countries, but this approach has limitations, with breast cancer screening only reducing mortality by about 20% and a high incidence of overdiagnosis and unnecessary treatment.
Led by Suzette, a breast cancer specialist and associate professor of medical oncology at the Department of Cancer Medicine at the Institut Gustave Roussy in Villejuif, France The “MyPeBS” trial led by Delaloge, which aims to improve breast cancer screening through personalized risk assessment strategies, is one of the largest studies of its kind worldwide to date, conducted in six different countries and involving more than 53,000 women.
This randomized controlled study will compare two groups of women:
One group followed current standard breast screening procedures;
The other group used a personalized risk assessment screening strategy.
Of the women in the study, half will have their saliva samples tested for DNA.
The researchers will use a polygenic risk score, combined with other risk factors, to assess each woman’s risk of breast cancer with high precision.
For high-risk women, more risk reduction measures may used;
For low-risk women, it is possible to reduce the number of unnecessary mammograms, thereby reducing the harm caused by unnecessary tests.
If the trial results prove that risk-based screening is as good or better than standard screening, it could revolutionize breast cancer prevention.
9. Tackling malnutrition caused by climate change through “home gardening”
Led by Ina Danquah, a nutrition scientist at the University of Bonn in Germany, ALIMUS is a multicenter, cluster-randomized controlled trial to study the effects of climate change on body nutrition, particularly in areas dependent on staple crops such as maize, wheat and sorghum.
These crops are experiencing declining levels of nutrients such as zinc, iron, selenium and protein due to the effects of climate change, posing a threat to children under five and women of childbearing age.
ALIMUS promotes home gardening in conjunction with nutritional health counseling to increase dietary diversity to compensate for the loss of nutrients from staple food crops.
In southeastern Kenya and rural Burkina Faso, families encouraged to grow vegetables and fruit near their homes.
These horticultural designs take into account local preferences, such as sweet potatoes and fast-growing fruits, and use only organic methods, avoiding the use of chemical fertilizers and pesticides.
The trial began in 2020 but delayed due to the COVID-19 pandemic, with baseline data collected in 2021.
The project is in its final stages, involving 300 intervention and 300 control families in each country.
With results expected in mid-2025, the team hopes the findings will provide new strategies to combat climate change-related malnutrition.
If successful, the model could applied more widely in regions facing similar climate challenges.
The project also aims to integrate its methods into regular practices in the local health and agriculture sectors, ensuring that the positive impact continues after the trial is over.
10. Treating autism with mobile games
Autism, also known as Autism Spectrum Disorder (ASD), a complex group of neurodevelopmental disorders characterized by significant difficulties in social interaction and communication skills, as well as restricted, repetitive patterns of behavior.
There is no cure for autism, but with early intervention and support, a person’s quality of life can significantly improved.
A mobile game designed by Dennis P. Wall, a professor of pediatric and biomedical data science at Stanford University School of Medicine, and his team can help increase social eye contact and attention in children with autism while reducing their limited interest and anxiety.
The game establishes an effective social interaction between the caregiver and the child, helps reduce stress for parents, and relieves symptoms of autism in the child.
Importantly, the data collected as the game runs can used to train AI tools for understanding autism signals to improve engagement and treatment outcomes for children with autism.
The researchers have enrolled children with autism between the ages of 2 and 8 for a clinical trial.
Researchers hope that through this learning game, not only can help autistic children better adapt to society, but also provide effective auxiliary tools for parents, so as to jointly promote the growth and development of children.
11. Using cannabis to treat mental illness
A research project called Stratification and Treatment in Early Psychosis (STEP), led by Philip McGuire, professor of psychiatry at Oxford University’s Department of Psychiatry, The aim was to study the effects of the use of cannabidiol (CBD, a component of the cannabis plant), which has approved for the treatment of severe epilepsy, in combination with prescription antipsychotic drugs in different subpopulations of psychiatric patients.
STEP consists of three clinical trials involving 30 research centers in 11 countries. These trials will evaluate approximately 1,000 participants with psychosis before and after CBD treatment using a range of neuroimaging techniques, such as magnetic resonance imaging and spectroscopy, to elucidate the effects of CBD.
By 2025, researchers expected to have preliminary results on the efficacy, safety, and tolerability of CBD in psychosis.
The researchers hope the study will shed light on whether people can use CBD to prevent mental illness.
