Category: 8. Health

In a wholly new approach to cancer treatment, Northwestern University biomedical engineers have doubled the effectiveness of chemotherapy in animal experiments.

Instead of attacking cancer directly, the first-of-its-kind strategy prevents cancer cells from evolving to withstand treatment — making the disease easier to target with existing drugs. Not only did the approach fully wipe out the disease to near completion in cellular cultures, but it also dramatically increased the effectiveness of chemotherapy in mouse models of human ovarian cancer.

The study was published today (July 22) in the Proceedings of the National Academy of Sciences.

“Cancer cells are great adapters,” said Northwestern’s Vadim Backman , who led the study. “They can adapt to almost anything that’s thrown at them. First, they learn to evade the immune system. Then, they learn how to adapt to chemotherapy, immunotherapy and radiation. When they resist these treatments, they live longer and acquire mutations. We did not set out to directly kill cancer cells. We wanted to take away their superpower — removing their inherent abilities to adapt, to change and to evade.”

Backman is the Sachs Family Professor Biomedical Engineering and Medicine at Northwestern’s McCormick School of Engineering , where he directs the Center for Physical Genomics and Engineering. He also is a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University , the Chemistry of Life Processes Institute and the International Institute for Nanotechnology .

Chromatin is key to cancer’s survival

Cancer has many distinctive features, but one trait underlies them all: its relentless ability to survive. Even as it is bombarded by the immune system and harsh medical treatments, cancer might shrink or slow its growth, but it rarely disappears. While genetic mutations contribute to this resistance, mutations occur much too slowly to explain cancer cells’ rapid survival response.

In a series of studies, Backman and his team discovered a fundamental mechanism that explains this ability. The intricate organization of genetic material, called chromatin, dictates cancer’s ability to adapt and survive in the face of the most potent drugs.

Chromatin — a group of macromolecules including DNA, RNA and proteins — determines which genes are suppressed or expressed. To fit the two meters of DNA that comprises the genome within just one hundredth of a millimeter of space inside a cell’s nucleus, chromatin is packed extremely tight.

Through a combination of imaging, simulations, systems modeling and in vivo experiments, Backman’s team discovered that the three-dimensional architecture of this packing not only controls which genes are expressed and how cells respond to stress, but it also allows cells to physically encode memories of gene transcription patterns into the geometry of the packing itself.

The genome’s 3D arrangement acts like a self-learning system, much like a machine learning algorithm. As it learns, this arrangement constantly reshapes into thousands of nanoscopic chromatin packing domains. Each domain stores part of a cell’s transcriptional memory, which dictates how the cell functions. Throughout one’s life, these cell-specific chromatin domains are formed, strengthened by cellular experiences, stored and rewritten. Problems with this transcriptional memory can lead to diseases such as cancer and Alzheimer’s disease and might even drive aging.

In the case of cancer, when chromatin packing is disordered, a cell demonstrates more plasticity — or an increased ability to adapt — enabling them to learn to resist treatments such as chemotherapy.

Reprogramming chromatin to boost chemotherapy

In the new study, Backman and his team developed a new computational model that uses physics to analyze how chromatin packing influences a cancer cell’s odds of survival against chemotherapy. After applying the new model to various types of cancer cells and chemotherapy drug classes, the team found it could accurately predict cell survival — before treatment even began.

Because chromatin packing is critical for cancer cell survival, the researchers wondered what might happen if they changed the packing architecture. Instead of developing new drugs, they screened hundreds of existing drug compounds to find candidates that could alter the physical environment inside cell nuclei to modulate chromatin packing. Ultimately, the team selected celecoxib, an FDA-approved anti-inflammatory drug that is already on the market. Often prescribed to treat arthritis and heart conditions, celecoxib has a side effect of altering chromatin packing.

“Several drugs, including celecoxib, can regulate chromatin and repress plasticity,” Backman said. “With this approach, we now can design strategies that synergize with chemotherapy or other existing therapies. The important finding is the concept itself. This particular drug just proves the point.”

“This study opens up novel therapeutic avenues to treat cancer that can supplement existing treatments,” said Rachel Ye, a graduate student in Backman’s laboratory . “It is exciting to see how we are unraveling the mysteries of genome organization through multidisciplinary approaches, and this paper is a strong result of that effort.”

Experimental results

According to Backman, celecoxib and similar drugs could become a new class of compounds, called Transcriptional Plasticity Regulators (TPRs), designed to modulate chromatin conformation to prevent cancer cells’ adaptive abilities. The researchers found that combining celecoxib with standard chemotherapy caused a substantial increase in the number of cancer cells that died.

After proving its effectiveness in cellular cultures, Backman and his team wanted to demonstrate its potential in a more realistic biological system. The team combined paclitaxel (a common chemotherapy drug) with celecoxib in a mouse model of ovarian cancer. The experiments revealed that the combination reduced the cancer cells’ adaptation rates and improved the inhibition of tumor growth — outperforming paclitaxel alone.

“The animal model that we used has incredible predictive power for what happens in humans,” Backman said. “When we treated them with a low dose of chemotherapy, the tumors continued to grow. But, as soon as we combined the chemotherapy with the TPR candidate, we saw much more significant inhibition. It doubled the efficacy.”

By making chemotherapy more effective, the new strategy potentially could also enable physicians to prescribe lower doses of chemotherapy for their patients. Lower, yet still effective, doses could reduce the burden of chemotherapy’s infamously difficult side effects. That would mark a significant improvement in patients’ overall comfort and experience during cancer treatment.

“Chemotherapy can be so hard on the body,” Backman said. “A lot of patients, quite understandably, sometimes choose to forego chemotherapy. They don’t want to suffer in order to live a few months longer. Maybe reducing that suffering would change the equation.”

Future directions for other diseases

Backman only has focused on cancer so far, but he thinks modulating chromatin conformation might be the key to treating various complex diseases, including heart disease, neurodegenerative diseases and more. Although most cells in a multicellular organism share the exact same genome, there are hundreds of cell types such as bone, neurons, skin, heart tissue, blood and so on. Understanding the physical rules governing how so many different types of cells, with such different functions, can result from the same instruction set is crucial; the conformation of chromatin and the cellular transcriptional memory are what allow all of these different cell types to “remember” which genes to express in order to perform their particular cellular function properly and to work coherently with the cells around them.

Backman posits that some complex diseases, rather than being caused entirely by genetic mutations, may be rooted both in mutations and in cells’ losing their correct transcriptional memories. The loss of a cell type-specific transcriptional lineage in neurons has been associated with early stage neurodegeneration, for example. Cells can also forget which genes to express for normal function when they undergo stress, and that incorrect expression may then become written into the cellular memory, leading to loss of cell function or even disease. Reprogramming chromatin conformation could help restore cells’ correct memories, potentially enabling them to return to a normal state.

“In many diseases, cells forget what they should be doing,” Backman said. “Many impactful diseases of the 21st century are, to a large extent, related to cell memory. Each cell in our body has several thousand chromatin domains, which are actual physical elements of transcriptional memory. The computational complexity that happens in every single cell is equivalent to a 1984 Apple computer. Cells maintain memory for a long time, but they can also develop spurious memories or lose memories. Cancer cells take that to the extreme. I think what we have found here is the source code of cell memory.”

The study, “Leveraging chromatin packing domains to target chemoevasion in vivo,” was supported by the National Institutes of Health (grant numbers U54CA268084, U54CA193419, R01CA228272, R01CA225002, R01CA155284, R01CA165309, T32GM132604, T32GM008152 and T32HL076139), National Science Foundation (grant numbers EFMA-1830961, EFMA-1830968, EFMA-1830969, CBET-1249311, EFRI-1240416, DGE-0824162 and DGE-184216), the Lefkovsky Innovation Award and the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust.

UNIVERSITY PARK, Pa. — Almost 200 million people, including children, around the world have endometriosis, a chronic disease in which the lining of the uterus grows outside of the uterus. More severe symptoms, such as extreme pain and potentially infertility, can often be mitigated with early identification and treatment, but no single point-of-care diagnostic test for the disease exists despite the ease of access to the tissue directly implicated. While Penn State Professor Dipanjan Pan said that the blood and tissue shed from the uterus each month is often overlooked — and even stigmatized by some — as medical waste, menstrual effluent could enable earlier, more accessible detection of biological markers to help diagnose this disease.

Pan and his group developed a proof-of-concept device capable of detecting HMGB1, a protein implicated in endometriosis development and progression, in menstrual blood with 500% more sensitivity than existing laboratory approaches. The device, which looks and operates much like a pregnancy test in how it detects the protein, hinges on a novel technique to synthesize nanosheets made of the atomically thin 2D material borophene, according to Pan, Dorothy Foehr Huck & J. Lloyd Huck Chair Professor in Nanomedicine and corresponding author of the study detailing the team’s work, published this week (July 17) on the cover of ACS Central Science.

“Despite the significant potential of menstrual effluent as a diagnostic tool for women’s health, it often faces substantial challenges due to social stigma and limited access to affordable diagnostic methods,” said Pan, who is a professor of nuclear engineering and of materials science and engineering. He is also affiliated with the Departments of Biomedical Engineering and of Radiation Oncology.

Existing diagnostic approaches involve intravenous blood tests and laboratory analyses coupled with imaging studies and extensive patient history collection for clinicians to make a definitive diagnosis. Such challenges contribute to delays in diagnosing endometriosis, with one study of 218 women revealing a delay of up to 12 years in the United States, he explained.

“By leveraging the novel 2D material borophene, our approach offers a unique opportunity to reduce menstrual stigma while advancing women’s health,” Pan said.

Borophene is a derivative of the chemical element boron similar to the more commonly researched graphene, a lightweight 2D material made from carbon, Pan said. Borophene, however, boasts an advantage over graphene.

“Work from my group demonstrates that borophene is highly biocompatible and a biodegradable material, making it highly suitable for biomedical applications,” Pan said, but he noted that fabricating the pure form of the material can pose challenges. Traditional methods involve several steps, which can degrade the quality and yield of the desired resulting product, and harsh solvents, like isopropyl alcohol, that can make the product unsuitable for biomedical applications.

In this study, the researchers swapped out the alcohol solvent for water. They dispersed powdered boron in the water, breaking down the chemical and reforming it into “pristine” nanosheets, according to Pan. The team then fixed antibodies that would recognize the protein HMGB1 to the nanosheets.

“Think of planting a garden,” Pan said. “The ground — the nanosheets — must be even and clear of weeds before you can fertilize the soil — adding the antibodies. Then, you have the best environment to support the desired vegetables — the HMGB1 proteins. That was our goal here, to create a uniform foundation on which the antibodies could recognize and capture the HMGB1 proteins.”  

Pan and his team used multiple imaging and chemical analysis techniques to validate that the antibodies correctly caught and bound to HMGB1, the protein implicated in endometriosis.

The researchers arranged the validated nanosheets into a test device, similar to a pregnancy test that displays either one line if negative or two if positive. As the blood sample flows over the test strip, if any HMGB1 proteins are present, they bind to the antibodies, which darkens the test strip.

To test the sensitivity of the device, the researchers spiked menstrual blood with various concentrations of HMGB1 and found the test successfully detected the protein at low concentrations with five times more sensitivity compared to existing laboratory tests that require extensive preparation and analysis.

“Clinical evidence indicates that HMGB1 levels in menstrual blood are significantly elevated in individuals with endometriosis compared to healthy controls,” Pan said. “However, early-stage or asymptomatic cases may present with only modest increases — that’s why high sensitivity to low HMGB1 concentrations is essential. Early detection is critical for timely intervention. Unlike other laboratory-based tests, our approach balances sensitivity with practicality for settings without centralized medical access and laboratory facilities, addressing unmet needs in endometriosis screening.”

Pan said the test could even be integrated into menstrual pads, enabling discreet and convenient monitoring of HMGB1 levels at home.   

“The ability to detect critically important biomarkers via a decentralized platform, like our approach, empowers patients with facilitating widespread use in more rural areas or settings without expansive medical resources,” Pan said. “This study highlights the broader research opportunities essential for realizing next-generation biotechnologies, with 2D materials at their core, and I’m excited about the potential of this highly promising class of nanomaterial for advanced health care applications.”

Next, the researchers said they plan to scale up their approach for clinical studies, improve the device’s sensitivity even further, and expand the test to detect additional disease biomarkers such as HPV and cervical cancer.

Other contributors, all who work in or completed work as students in Pan’s laboratory at Penn State, include co-first authors Satheesh Natarajan, postdoctoral researcher in nuclear engineering, and Ketan Dighe, graduate student in biomedical engineering; Teresa Aditya, assistant research professor of nuclear engineering; Pranay Saha, postdoctoral researcher in nuclear engineering; David Skrodzki, graduate student in materials science and engineering; Purva Gupta, who graduated from Penn State with a bachelor of science in biomedical engineering in May and who helped support the effort to establish free menstrual product dispensers across University Park in 2023; Nivetha Gunaseelan, doctoral student in biomedical engineering; Shraddha Krishnakumar, doctoral student in biomedical engineering. Dighe, Gupta and Gunaseelan were awarded the inaugural National Academy of Inventors Dr. Barry B. Bercu Biomedical Collegiate Inventor Prize in 2024 for their work on this project.

The Centers for Disease Control and Prevention, the U.S. National Science Foundation, the Department of Defense Congressionally Directed Medical Research Program and the National Institutes of Health supported this work.

At Penn State, researchers are solving real problems that impact the health, safety and quality of life of people across the commonwealth, the nation and around the world.

For decades, federal support for research has fueled innovation that makes our country safer, our industries more competitive and our economy stronger. Recent federal funding cuts threaten this progress.

Learn more about the implications of federal funding cuts to our future at Research or Regress.

An experimental, hormone-free male birth control pill has just passed its first safety test in humans.

The trial included 16 people and was only intended to test whether the drug reached adequate levels in the body, as well as whether it triggered any serious side effects, such as concerning changes in heart rate, hormone function, inflammation, mood or sexual function.

MIAMI, FLORIDA (July 22, 2025) – LaShae Rolle, 27, is a competitive powerlifer who could squat 441 pounds, bench 292 pounds and deadlift 497 pounds. She is also a breast cancer survivor and researcher and the lead author on a first-of-its kind study documenting elite-level strength training during active breast cancer treatment.

The study challenges the long-held belief that cancer patients should stick to low- or moderate-intensity exercise and suggests that with individualized and symptom-informed exercise planning, even powerlifting can be safe and beneficial. The findings appear in the July 2024 issue of the journal, Lifestyle Medicine.

Diagnosed in 2024 with stage 2B estrogen receptor-positive breast cancer, Rolle had no genetic predisposition to breast cancer. A competitive powerlifter, strength wasn’t just physical for her — it was personal.

“Strength training has been central to my identity as both an athlete and a rising lifestyle oncology researcher,” she said. “During cancer, it became a way to stay connected to who I am and to feel in control of my body and mind.”

Rolle’s treatment regimen included chemotherapy, a mastectomy and radiation. Beyond that, her research team at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, designed a periodized strength training program to align with her chemo cycles.

• High-intensity days were scheduled before chemo infusions and focused on squats, bench press and deadlifts.
• Moderate days aligned with mid-cycle sessions involving accessory movements like rows and shoulder presses.
• Recovery days included light mobility and therapy work after an infusion.

Each session was adjusted based on real-time symptom tracking and perceived exertion (RPE), creating a feedback loop that prioritized safety and performance.

By the end of treatment, Rolle had retained 93% of her squat strength and 87% of her bench press and deadlift strength. These numbers are rare for someone undergoing chemotherapy and demonstrate the feasibility of high-intensity training when carefully managed.

“I’m proud I kept going,” she says. “Modifying my sessions around chemotherapy cycles helped me keep training safely, and physically, it gave me moments of normalcy even when everything else felt uncertain. . . Documenting everything on video and in a training diary kept me accountable and reminded me I was still strong,” she added. “I am still in awe when I look back at videos of me lifting over 400 pounds in the midst of chemotherapy.”

Changing the Game for Elite Athletes

Previous studies have shown that moderate-intensity aerobic and resistance training can reduce fatigue, improve physical function and alleviate treatment-related symptoms in cancer patients. But that research focused on general populations or survivors, post-treatment. High-intensity modalities like powerlifting remain underexplored.

“LaShae’s journey is a powerful reminder that survivorship is not just about recovery—it’s about reclaiming strength, identity and purpose. Her commitment to powerlifting exemplifies how movement can be a form of healing, empowerment and advocacy.” said Rolle’s primary mentor, Tracy Crane, Ph.D., R.D.N., co-leader of the cancer research program and director of Lifestyle Medicine, Prevention and Digital Health at Sylvester.

For Rolle, being a part of this case study confirmed how critical individualized, flexible programs are for survivors. “I’m absolutely encouraged to keep lifting and to keep advocating for evidence-based exercise as part of cancer care,” she said.

Read more about Sylvester research on the InventUM blog and follow @SylvesterCancer on X for the latest news on its research and care.

# # #

Authors: A complete list of authors is available in the paper.

Article Title: Exercising Through Breast Cancer: A Case Study on Strength Training During Active Treatment

DOI: 10.1002/lim2.70034

Funding: The authors received no specific funding for this work.

Disclosures: The authors declare no conflicts of interest.

# # #

Editor’s Note:
The Case Challenge series includes difficult-to-diagnose conditions, some of which are not frequently encountered by most clinicians, but are nonetheless important to accurately recognize. Test your diagnostic and treatment skills using the following patient scenario and corresponding questions. If you have a case that you would like to suggest for a future Case Challenge, please email us at ccsuggestions@medscape.com with the subject line “Case Challenge Suggestion.” We look forward to hearing from you.

Background

A 35-year-old man presents to the neurology clinic due to abnormal movements over the past 6 years. The involuntary movements began in the right upper limb, followed sequentially by the left upper limb, left lower limb, and finally the head and neck. The movements occur during wakefulness and are absent in sleep. They are described as jerky and nonpurposeful. His gait has assumed a dancelike character. He also has had behavioral changes that include frequent outbursts of anger, aggressive behavior, depressive mood, and insomnia. His abnormal movements are aggravated during outbursts of anger and disturbances in mood.

He has no weakness in any limbs but is unable to perform regular household activities. Family members have also noted memory impairment. He has been unable to continue his work as a machine operator for the past 3 months.

He has no history of psychoactive drug intake, including phenytoin, phenothiazines, haloperidol, L-dopa, lithium, isoniazid, amphetamines, tricyclic antidepressants, or any other relevant drugs. He reports no history of chest pain, breathlessness, or joint pain. His family history includes a paternal grandfather and father who had similar forms of abnormal movements and died at the age of 60 years and 55 years, respectively.

The patient has five siblings (two brothers, three sisters). His elder brother died by suicide at age 25 years, and his elder sister died at age 33 years. Both had abnormal movements and abnormal behaviors. One of his younger sisters (age 22 years) also has similar abnormal movements and depressed attitude. His younger brother (age 17 years) and other younger sister (age 14 years) are healthy and symptom-free. The patient’s children, an 8-year-old son and a 10-year-old daughter, are symptom-free.

His past medical history is positive for hypertension, which is well controlled with lisinopril (20 mg daily). He has no surgical history. He does not smoke, drink, or use recreational drugs.

Physical Examination and Workup

A general examination reveals a pleasant man who is well built and in no acute distress. His blood pressure is 140/80 mm Hg, his heart rate is 78 beats/min, his respiratory rate is 12 breaths/min, his SpO₂ level is 98% on room air, and his body mass index (BMI) is 20. He is afebrile.

A cardiovascular examination reveals normal peripheral pulses and normal heart findings. A chest examination reveals normal auscultation and expansion. His abdomen is soft. Head, eyes, ears, nose, and throat (HEENT) examination findings are unremarkable. He does not have a skin rash. A visual examination reveals normal acuity, field, and fundi.

His affect is flat. A neurologic examination of the higher mental functions reveals that the patient is awake and alert, with normal orientation, attention, concentration, fund of knowledge, and language function. His memory is impaired, with recall one-third at 3 minutes. He has a normal past memory. His speech is normal. A cranial nerve examination reveals normal extraocular movements, increased blink rate, normal facial sensation, a symmetric face with abnormal fidgety movement, normal hearing, and normal palate movement. He has abnormal tongue movement and cannot protrude his tongue more than 20 seconds (darting tongue movement). He has normal shoulder shrug. No Kayser-Fleischer ring is noted during slit-lamp examination.

An examination of the motor system reveals decreased muscle tone, normal bulk, and 5/5 strength in both upper and lower extremities. No atrophy or fasciculation is noted. Deep tendon reflexes are normal (2+ with flexor planters). Sensory examination findings are normal. Finger-nose test findings are normal. An examination of the extrapyramidal system reveals reduced tone and involuntary choreoathetoid movements that affect both upper and lower extremities as well as his face. He has a dancing gait.

Diagnostic tests reveal normal complete blood cell count (CBC) and comprehensive metabolic panel findings. He has normal serum findings and urine copper levels. His erythrocyte sedimentation rate (ESR) is 22 mm/hr (reference range, 0-22 mm/hr). He has normal ECG findings, a normal thyroid-stimulating hormone (TSH) level, a normal transthoracic echo (with ejection fraction 65%), and normal chest radiography findings.

Brain MRI can be used to evaluate for selective atrophy of deep gray structures, to document disease burden, and to provide a baseline for future comparison. Whole-body 18-FDG PET/CT may be used to screen for occult neoplasm and paraneoplastic chorea, but this is exceedingly rare and typically subacute. NMDA receptor antibody panel may be used to investigate for autoimmune encephalitic chorea, but the features of this (ie, seizures, psychosis, and autonomic instability) are absent in this case. RPR and FTA-ABS may be used to evaluate for neurosyphilitic chorea, but this is also very uncommon and unnecessary without risk factors or acute symptoms.

In this patient, brain MRI reveals evidence of bilateral caudate atrophy, with increased intercaudate distance (Figure).

Figure.

Cerebrospinal fluid (CSF) examination findings are normal.

Discussion

This 35-year-old man has Huntington disease. He has insidious-onset, slowly progressive movement disorder, and movements are absent during sleep. His movements are described as choreoathetoid. He has family history that suggests autosomal dominant transmission. Apart from the movement disorder, he also has neuropsychiatric manifestations, with death at an early age in the family. A CT scan of the head revealed evidence of caudate nucleus atrophy. Brain MRI revealed evidence of caudate atrophy (Figure).

Figure.

In evaluating the differential diagnoses, the patient has no history of antipsychotic medication use to suggest tardive dyskinesia. He has no clinical or diagnostic evidence of infection or heart involvement, which makes Sydenham chorea unlikely. No acanthocytes were observed, helping to exclude neuroacanthocytosis. The strong family history of progressive abnormal movements and neuropsychiatric symptoms across generations supports a genetic etiology, specifically autosomal-dominant Huntington disease.

Huntington disease is a rare neurodegenerative disorder of the central nervous system (CNS) characterized by choreiform movements, behavioral and psychiatric disturbances, and dementia.^[1] Huntington disease is caused by an autosomal-dominantly inherited expansion of CAG trinucleotide repeats in the huntingtin (HTT) gene on chromosome 4; this leads to production of a mutant huntingtin (mHTT) protein, with an abnormally long polyglutamine repeat.^[2] Individuals with more than 39 CAG repeats develop the disease, whereas reduced penetrance is seen in those with 36-39 CAG repeats. The disease can be anticipated when the gene is passed down the paternal line, as in this case; a father with a CAG repeat length in the intermediate range may have a child with an expanded pathogenic repeat length. This is because sperm from males shows greater repeat variability and larger repeat sizes than somatic tissues. Mutant huntingtin protein leads to death and neuronal dysfunction through various mechanisms. Postmortem studies reveal diffuse atrophy of the caudate and putamen. The progressive worsening of Huntington disease leads to a bedridden state with cognitive deterioration, and death typically occurs about 20 years after the onset of symptoms.^[3]

Prevalence in the white population is estimated at 1 in 10,000 to 1 in 20,000. The mean age at symptom onset is 30-50 years. In some cases, symptoms begin before age 20 years, with behavior disturbances and learning difficulties at school; this is termed juvenile Huntington disease (Westphal disease).^[4] The first description, by Waters, dates to 1842. However, after a description in 1872 by George Huntington, it became known as Huntington chorea. In 1983, a linkage on chromosome 4 was established, and in 1993 the gene for Huntington disease was found.^[1]

Diagnosis of Huntington disease is confirmed by demonstration of autosomal dominant transmission or gene testing in the presence of clinical features.^[5]

The clinical features of Huntington disease consist of motor, cognitive, and neuropsychiatric manifestations. Huntington disease has a biphasic course of hyperkinetic phase with chorea in the early stages of disease that then plateaus into a hypokinetic phase, consisting of bradykinesia dystonia, balance issues, and gait disturbance. The younger-onset variant is associated with predominant bradykinesia.^[6] Cognitive disturbance can be seen many years before other symptom onset and is characterized by impaired emotion recognition, processing speed, and executive function abnormality. Neuropsychiatric symptoms widely vary, including apathy, anxiety, irritability, depression, obsessive-compulsive behavior, and psychosis. A lack of awareness of early and progressing behavioral, cognitive, and motor symptoms is a hallmark of Huntington disease. This unawareness is caused by the disease itself (specifically, impaired insight or anosognosia) and is not the result of intentional denial, avoidance, or suppression of symptoms.^[7] Therefore, a comprehensive history, including information from a knowledgeable family member/caregiver, is advisable.^[7]

Numerous conditions can mimic Huntington disease, including a spinal cerebellar ataxia 17, spinocerebellar ataxia 1-3, and Friedreich ataxia, which involve neuropathy. If seizures are also present, dentatorubropallidoluysian atrophy should be considered. Acanthocytes are seen in patients with neuroacanthocytosis.^[8-10] Isolated chorea can be seen in acquired conditions, including chorea gravidarum, systemic lupus erythematosus, antiphospholipid syndrome, thyrotoxicosis, postinfectious syndromes, polycythemia vera, and some drug use.

Genetic testing for the mHTT mutation can be either diagnostic or predictive.^[6] A diagnostic test may be performed when a patient presents with typical motor features of Huntington disease. Prior to testing, the patient should be informed about Huntington disease and its hereditary nature, as a positive test result has implications for the patient and family. Predictive testing is performed in asymptomatic patients, mostly for reproductive reasons.

Treatment of Huntington Disease

The optimal management of Huntington disease involves a multidisciplinary approach that includes neurology, nurses, physical therapy, speech-language pathology, and dietitians and other healthcare professionals. The goal is to optimize the quality of life based on the changing need of the patient. These consist of combined pharmacologic and lifestyle changes, including behavioral therapy. Symptoms may be worsened by stress, fatigue, and intercurrent disorders (eg, anxiety, digestive disorders, infectious or painful conditions), so these aspects must be assessed and treated alongside the primary symptoms of Huntington disease.^[3]

In clinical practice, information about symptoms should be obtained from both the patient and caregivers, since patients may have impaired awareness of their condition.^[11] Identifying coexisting psychiatric symptoms, comorbid medical conditions, and environmental factors is crucial.^[11] Educating caregivers about the nature and presentation of symptoms and methods to modify triggers is also vital.^[11] Medication choices should be guided by coexisting symptoms and disease stage, and regular reassessment of drug need and potential for dose reduction is important because of adverse effects that can mimic disease progression.^[11]

Nonpharmacologic interventions, including behavioral therapies and environmental modifications, should be prioritized for neuropsychiatric symptoms in Huntington disease. Pharmacologic agents may be considered if these measures are insufficient, and consultation with a psychiatrist knowledgeable in Huntington disease is recommended for individuals whose symptoms are resistant to standard pharmacologic therapy.^[11]

Tetrabenazine and its modified version, deutetrabenazine, are commonly used to treat choreiform movements. Side effects of tetrabenazine can include depression, anxiety, sedation, sleep problems, restlessness, and parkinsonism.^[7] Citalopram is a selective serotonin reuptake inhibitor used to manage depression. Modafinil and atomoxetine are used to manage apathy. Tiapride, although unavailable in the United States, is considered a first-line treatment option for chorea outside the United States.^[7] Other antipsychotics such as olanzapine, risperidone, and quetiapine are also used to manage chorea. Risperidone may also help with psychomotor restlessness, and olanzapine and quetiapine can have additional benefits like weight gain (which can be desirable in Huntington disease) and mood stabilization. Haloperidol has also shown effectiveness.^[7] Medications used to suppress chorea (eg, tetrabenazine and deutetrabenazine and certain antipsychotics) should be used sparingly and mainly for subjectively disabling hyperkinesias, starting at low doses and titrating gradually. They make take 4-6 weeks to show results.^[7] The choice of medication depends on the individual patient’s symptoms, tolerability, and co-existing conditions.^[7]

Evidence regarding the treatment of psychiatric symptoms in Huntington disease is limited, with recommendations often based on expert opinion owing to a lack of robust controlled studies.^[7,11] Nonpharmacologic interventions such as cognitive-behavioral therapy and psychodynamic therapy are recommended, especially for depression, anxiety, obsessive-compulsive behaviors, and irritability. Behavioral strategies (eg, structured routines and distraction) are important for managing irritability and agitation.^[3,11]

• Depression: Selective serotonin reuptake inhibitors (SSRIs) such as citalopram, fluoxetine, paroxetine, sertraline, and venlafaxine are recommended as pharmacologic options.^[3,7] Mianserin (unavailable in the United States) or mirtazapine are alternatives, particularly in patients with sleep disruption.^[3,7,11] Electroconvulsive therapy (ECT) may be considered for severe or resistant cases, although it can significantly impair short-term memory.^[3,7]
• Anxiety: SSRIs or serotonin-noradrenaline reuptake inhibitors (SNRIs) are first-line treatments, especially when anxiety coexists with depression.^[3,11] Mirtazapine is an option in patients with sleep disorders.^[11] Long-term use of benzodiazepines is generally discouraged for ambulatory individuals because of the risk of falls and dependence but can be used short-term or as needed.^[3,11]
• Obsessive-compulsive behaviors/perseverations: For true obsessive-compulsive phenomena, SSRIs are considered first-line treatment.^[3] Olanzapine and risperidone may also be valuable for ideational perseverations, particularly if associated with irritability.^[3] Clomipramine is an option, especially if needed for coexisting obsessive perseverative behaviors.^[11]
• Irritability and aggression: SSRIs are a first-line treatment.^[3] For aggressive behavior, neuroleptics are recommended.^[3,7] Mood stabilizers (eg, valproate, lamotrigine, lithium, carbamazepine) can be added if irritability is resistant to other treatments or for mood lability. Risperidone and olanzapine may help reduce irritability.^[3,7]
• Psychosis (hallucinations/delusions): Second-generation neuroleptics (antipsychotics) are the first-line pharmacologic treatment.^[3,7,11] Options include olanzapine, risperidone, quetiapine, aripiprazole, and haloperidol.^[7] Clozapine may be considered for severe or resistant cases, particularly in akinetic forms of Huntington disease but requires regular monitoring.^[3,7,11] Underlying causes, such as the use of psychotropic agents or somatic triggers, should be investigated and addressed.^[3,11]
• Apathy: Personalized cognitive stimulation and structured routines and activities are recommended.^[3,7,11] If depression is suspected as a contributor, an SSRI should be tried.^[3,11] In patients without depression, activating antidepressants or stimulant drugs (eg, methylphenidate, atomoxetine, modafinil) may be considered.^[11] Sedative medications may increase apathy, so their dosage should be monitored or reduced.^[3,11]

Currently, no pharmacological treatment is specifically recommended for cognitive symptoms in Huntington disease.^[3,7] Rehabilitation strategies, including speech therapy, occupational therapy, cognitive and psychomotor therapy, may help transiently improve or stabilize cognitive functions.^[3,7] Coping strategies can be useful as an alternative to medication. Certain medications, such as sedative drugs, neuroleptics, and tetrabenazine, can negatively affect memory, executive functions, and attention.^[3]

Apart from symptomatic treatment, pharmacologic agents have failed to show benefit in clinical trials as disease-modifying agents. The most promising approaches in regard to disease modification are emerging therapies aimed at lowering levels of mHTT by targeting either the DNA or RNA of the mHTT gene.^[12] RNA-targeting using antisense oligonucleotides (ASOs) have shown disappointing results in clinical trials. This has shifted significant research focus and toward orally available small molecules that modify HTT mRNA splicing, thereby reducing mHTT protein production. DNA-targeting approaches using gene editing tools like CRISPR/Cas9, while demonstrating success in preclinical models, remain in the early stages of development.^[13,14]

The patient in this case was diagnosed with Huntington disease with CAG repeat 78. He was started on tetrabenazine for abnormal movements and citalopram for depression. He opted to apply for federal disability. His children are asymptomatic, and the family decided not to investigate until symptoms develop or they are age 18 years.

Editor’s Note: This article was created using several editorial tools, including generative AI models, as part of the process. Human review and editing of this content were performed prior to publication.

Model proved more accurate for people of European ancestry

The PRS model proved more accurate for people of European ancestry compared to South Asians. The model, created using genetic data from over five million individuals of various backgrounds, was found to be twice as effective as previous models.

By integrating the influence of hundreds of thousands of genetic variants, it evaluates an individual’s risk of obesity, serving as a robust early-warning tool to inform preventive lifestyle adjustments.

“What makes the score so powerful is its ability to predict, around the age of five, whether a child is likely to develop obesity in adulthood, well before other risk factors start to shape their weight,” said Dr. Roelof Smit, lead author and assistant professor at the University of Copenhagen’s NNF Centre for Basic Metabolic Research.

Dr. Chandak told TNIE, “This is one of the most extensive multi-ancestry studies ever conducted. It identifies genetic variants accounting for 18 to 20% of the genetic risk for obesity, almost triple what we previously knew. For India, it shows that precision prevention is possible but must go hand in hand with behaviour change.”

He added that the samples tracked over the years were mainly healthy individuals, and those who developed other diseases were excluded from the initial genetic assessments. The research also confirmed that obesity in Indians, which is often abdominal and visceral, follows a different genetic trajectory than in Europeans.

The senior geneticist said, “Many obesity-linked gene variants identified in European populations showed limited impact on Indians. In the future, we must create PRS models specific to Indian groups.”

How much can six days of eating just oats, milk, and water change your gut microbiome? 

According to a recent exploratory study published in eGastroenterology, the answer is more complex than expected. Researchers from KU Leuven and collaborating institutions conducted a tightly controlled dietary intervention, known as the “Oatmeal Study”, to examine whether restricting food variety could induce convergence in the gut microbiota across individuals. Surprisingly, while participants’ diets became nearly identical, their microbiomes did not follow suit. It highlights the importance of individualized responses and underscores the limitations of one-size-fits-all approaches in microbiota-targeted dietary interventions.

The 21-day study followed 18 healthy adults from Flanders, Belgium. It was structured into three phases: a 7-day baseline with habitual diets, a 6-day intervention where participants consumed only oat flakes, whole milk, and still water, and an 8-day follow-up where normal diets resumed. Daily stool samples and weekly blood draws were collected, enabling quantitative microbiome profiling through 16S rRNA gene sequencing paired with flow cytometry. Participants also maintained detailed food diaries, allowing the researchers to link dietary intake with microbial and metabolic outcomes. Notably, microbiome analysis accounted for the estimated 2-day lag between ingestion and egestion, enhancing data accuracy.

Key findings

• Dietary Convergence Achieved

The intervention significantly reduced food intake diversity. Analysis confirmed a sharp drop in dietary variation during the 6-day oat-only phase. Macronutrient intake also declined, with calories reduced by 31.5%, and significant decreases in fat, protein, and carbohydrate consumption. Interestingly, fibre intake increased due to the oat-based diet.

• Microbiome Did Not Converge Across Individuals

One of the study’s most surprising findings was the lack of interindividual convergence in gut microbiota. Instead of becoming more similar, microbiome profiles remained distinct and, in some cases, became even more divergent. The effect size (ES) of the dietary intervention on genus-level microbiome variation was 3.4%, but with a striking interindividual range (1.67–16.42%). This undermines the long-held notion that uniform dietary input will yield uniform microbial outcomes and supports the view that host-specific factors such as genetics, baseline microbiota, and metabolic capacity dominate responses to dietary modulation.

• Shift Toward Potentially Dysbiotic Enterotype

A notable shift was observed in microbial community structure. The prevalence of the Bacteroides2 (Bact2) enterotype-often associated with dysbiosis-increased significantly during the intervention, while the more stable Bacteroides1 (Bact1) community declined. These changes were reversed after participants resumed their normal diets. This Bact2 dominance coincided with a marked drop in Faecalibacterium, a butyrate-producing genus known for its anti-inflammatory properties. Given its association with reduced microbial diversity and inflammatory states, the transient rise of Bact2 raises concerns about the health effects of such restrictive diets.

• Microbial Load and Diversity Decreased

Faecal microbial load fell by more than 30% during the intervention, without changes in stool moisture or transit time. This aligns with the reduced caloric intake observed and echoes prior findings showing decreased bacterial biomass under caloric restriction. Furthermore, overall microbiome diversity-as measured by the Shannon index-dropped significantly during the intervention, a pattern that correlates with less mature and resilient microbial ecosystems.

•  Individual Microbiomes Reacted Uniquely

Despite the group-level trends, individuals responded very differently to the same diet. Some showed marked changes in microbial composition, while others remained relatively stable. The authors attempted to identify predictive factors, such as gender or baseline microbiota diversity, but no clear predictors emerged after correction for multiple testing. This unpredictability reinforces the complexity of host–microbiota interactions and suggests that personal traits, rather than just diet, drive microbial changes. Personalized nutrition may be essential to achieving targeted microbiome modulation.

Interpretations and implications

The findings from this study challenge the intuitive belief that simplification of diet should naturally lead to convergence in microbial communities. Instead, they illustrate the resilience of individual microbiota and the importance of pre-existing microbial states in shaping responses to environmental changes. It highlights: (1) Personalized Diets Over Universal Prescriptions: Even under tightly controlled dietary conditions, individuals show unique microbial responses. Future interventions should consider personalized baseline assessments to guide dietary recommendations; (2) Caution in Using Enterotypes as Biomarkers: While Bact2 has been linked with dysbiosis and disease, its transient appearance here in healthy individuals suggests caution when interpreting enterotypes as fixed or pathological markers; (3) Beyond Calories and Macronutrients: The study supports the concept of “successional maturation” of the microbiome, where microbial development is shaped not just by nutrient intake, but also by substrate diversity and transit time. These factors may be equally important as caloric content in shaping gut health.

In conclusion, the “Oatmeal Study” underscores that even radical reductions in dietary diversity do not necessarily bring about uniformity in gut microbiota. Instead, the human microbiome exhibits resilience and individuality, governed by complex host–microbe dynamics. While dietary convergence increased the prevalence of a potentially dysbiotic community type and reduced microbial diversity, the overall effect was modest and highly variable between individuals. These insights are essential for the design of future microbiome-targeted interventions, which must account for individual variability and ecological context.

Brain aging may have sped up during the pandemic, even in people who didn’t get sick from Covid, a new study suggests.

Using brain scans from a very large database, British researchers determined that during the pandemic years of 2021 and 2022, people’s brains showed signs of aging, including shrinkage, according to the report published in Nature Communications.

People who got infected with the virus also showed deficits in certain cognitive abilities, such as processing speed and mental flexibility.

The aging effect “was most pronounced in males and those from more socioeconomically deprived backgrounds,” said the study’s first author, Ali-Reza Mohammadi-Nejad, a neuroimaging researcher at the University of Nottingham, via email. “It highlights that brain health is not shaped solely by illness, but also by broader life experiences.”

Overall, the researchers found a 5.5-month acceleration in aging associated with the pandemic. On average, the difference in brain aging between men and women was small, about 2.5 months.

“We don’t yet know exactly why, but this fits with other research suggesting that men may be more affected by certain types of stress or health challenges,” Mohammadi-Nejad said.

Brains shrink as people age. When gray matter shrinks prematurely, it can lead to memory loss or judgment problems, although the pandemic study doesn’t show whether people with structural changes will eventually develop cognitive deficits.

The study wasn’t designed to pinpoint specific causes.

“But it is likely that the cumulative experience of the pandemic—including psychological stress, social isolation, disruptions in daily life, reduced activity and wellness—contributed to the observed changes,” Mohammadi-Nejad said. “In this sense, the pandemic period itself appears to have left a mark on our brains, even in the absence of infection.”

An earlier study on how teenagers’ brains were affected by the pandemic discovered a similar result. The 2024 research from the University of Washington found that boys’ brains had aged the equivalent of 1.4 years extra during the pandemic, while girls aged an extra 4.2 years.

In the new study, Mohammadi-Nejad and his team turned to the UK Biobank, a massive database which launched in 2006, to determine whether the pandemic had any impact on people’s brains. The database has been keeping track of anonymous health data from 500,000 volunteers who were recruited between 2006 and 2010, when the participants were between 40 to 69 years old. Thus far, the biobank has collected 100,000 whole body scans.

To develop a baseline model of normal aging, to compare with what might have occurred during the pandemic years, the researchers used imaging data from 15,334 healthy individuals that had been collected prior to the pandemic.

“We used this large dataset to teach our model what typical, healthy brain ageing looks like across the adult lifespan,” Mohammadi-Nejad explained.

Next the researchers turned to a group of 996 participants who had two scans, the second taking place on average 2.3 years after the first. Of these participants, 564 had both scans prior to the pandemic, which helped the artificial intelligence learn how the brain changes when there is no pandemic.

The other 432 had a second scan after the start of the pandemic, mostly between 2021 and 2022, allowing the researchers to investigate how the pandemic might have affected brain aging.

Although these second scans were done later in the pandemic, “they reflect brain changes that likely happened during the height of the pandemic, when people experienced the most disruption,” Mohammadi-Nejad said.

Other research has suggested that environmental factors might cause a person’s brain to age prematurely. One study conducted in the Antarctic tied living in relative isolation to brain shrinkage.

“The most intriguing finding in this study is that only those who were infected with SARS-CoV-2 showed any cognitive deficits, despite structural aging,” said Jacqueline Becker, a clinical neuropsychologist and assistant professor of medicine at the Icahn School of Medicine at Mount Sinai. “This speaks a little to the effects of the virus itself.”

And that may eventually help explain syndromes, such as long Covid and chronic fatigue, she said.

What we don’t know from this study is whether the structural brain changes observed in people who didn’t get Covid will amount to any observable changes in brain function, Becker said.

Adam Brickman, a professor of neuropsychology at Columbia University Vagelos College of Physicians and Surgeons, said the study is a compelling narrative, but “still a hypothesis.”

It doesn’t show whether the accelerated aging seen in people who didn’t get Covid will persist long term, said Brickman, who was not involved with the study.

If the brain indeed was changed by the pandemic in meaningful ways, then people might counter those changes by doing things that are healthy for the brain, he said.

“We know that exercise is good for the brain and keeping blood pressure at a healthy level, for example. We know that sleep and social interactions are important.”

Eight babies have been born in the United Kingdom using DNA from three people to prevent deadly hereditary diseases, a scientific breakthrough hailed by doctors but raising ethical concerns among some scientists as well as Christian groups, according to reporting by the BBC and Christian Today in the U.K.

The pioneering technique combines the egg and sperm from the parents with healthy mitochondrial DNA from a donor woman. While the method has been legal in the UK since 2015, these are the first confirmed cases where children were born free of mitochondrial disease — a group of often fatal conditions passed from mother to child that affect the body’s ability to produce energy. 

Mitochondria, tiny structures within cells, fuel essential functions in the body. Defective mitochondria can cause seizures, organ failure, and death in infants. About one in 5,000 babies is born with mitochondrial disease.

Parents involved in the procedures, conducted at Newcastle Fertility Centre, shared anonymous statements through the clinic. “After years of uncertainty this treatment gave us hope — and then it gave us our baby,” said the mother of a baby girl. Another parent, a mother of a baby boy, added, “The emotional burden of mitochondrial disease has been lifted, and in its place is hope, joy, and deep gratitude.”

The process, developed over a decade ago at Newcastle University and Newcastle upon Tyne Hospitals NHS Foundation Trust, involves fertilizing eggs from the mother and a donor with the father’s sperm. The nuclear DNA from the parents — determining traits like eye color and height — is then inserted into the donor egg, which contains healthy mitochondria. The resulting child has 99.9% of their parents’ DNA and 0.1% from the donor, a change that is passed to future generations.

According to two reports in the New England Journal of Medicine, 22 families have undergone the procedure, resulting in four boys, four girls, one set of twins, and one ongoing pregnancy. So far, the children are free of mitochondrial disease and meeting developmental milestones.

“This is the only place in the world this could have happened,” said Prof. Sir Doug Turnbull of Newcastle University to the BBC, crediting the combination of advanced science, legal framework, and NHS support.

However, not everyone sees this as an unqualified triumph. Christian groups and bioethics advocates have voiced concerns about the ethical implications, particularly regarding the destruction of embryos during the process.

“In the creation of a three-parent baby, two other embryos are destroyed, which means two individual human beings have their lives ended to create a third,” Catherine Robinson, spokesperson for Right To Life UK, told Christian Today.

Robinson also criticized calls by the Human Fertilisation and Embryology Authority (HFEA) to extend the legal window for experimenting on human embryos from 14 days to 22 days. “Human embryos should never be experimented on,” she said, adding, “It is even more disturbing to see the HFEA make the case for doing experiments on them even further into their development. At around 22 days, the central nervous system is formed and by 28 days, the developing heart can sometimes be seen beating.”

The ethical debate reflects deeper tensions between scientific progress and respect for human life at its earliest stages. While families facing mitochondrial disease see new hope, critics warn of a slippery slope toward “designer babies” and greater disregard for embryonic life.