Mitochondria are central regulators of cellular metabolism, redox balance, calcium signaling, and cell survival, making them essential for neuronal function. Because neurons rely heavily on mitochondrial oxidative phosphorylation to meet their high energetic demands, mitochondrial dysfunction has emerged as a key pathogenic driver in major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Defects in mitochondrial bioenergetics, excessive reactive oxygen species production, impaired mitochondrial dynamics, disrupted mitophagy, and dysregulated calcium handling collectively contribute to neuronal damage, synaptic dysfunction, and neuroinflammation. These insights have prompted growing interest in therapeutic strategies that directly target mitochondria to restore organelle homeostasis. Recent advances in chemical biology and nanomedicine have enabled the development of mitochondria-targeted ligands, peptide-based targeting systems, and carrier or nanotechnology-enabled delivery platforms designed to overcome biological barriers and selectively deliver therapeutic cargos to mitochondria within the central nervous system. In this Review, we summarize mitochondrial pathological mechanisms in neurodegenerative diseases and discuss emerging mitochondria-targeted therapeutic strategies, highlighting delivery technologies, therapeutic modalities, and translational challenges. Although most strategies remain at the preclinical or proof-of-principle stage, these advances are beginning to shape a conceptual framework for precision mitochondrial medicine, with the longer-term goal of developing disease-modifying interventions for neurodegenerative disorders.
Editorial: eHealth and personalized medicine in mental health and neurodevelopmental disorders: digital innovation for diagnosis, care, and clinical management
A new additive in the opioid supply is causing disastrous complications
Nature Medicine, Published online: 21 July 2026; doi:10.1038/s41591-026-04536-x
A new additive in the opioid supply is causing disastrous complications
Individualized antisense oligonucleotides for SCN2A-related developmental epileptic encephalopathy
Nature Medicine, Published online: 21 July 2026; doi:10.1038/s41591-026-04527-y
In two patients with SCN2A epileptic encephalopathy, treatment with personalized allele-selective antisense oligonucleotides led to a decrease in seizure frequency with a positive safety profile.
An iPSC-derived neural progenitor cell therapy for subacute spinal cord injury: a phase 1 trial with long-term follow-up
Nature Medicine, Published online: 21 July 2026; doi:10.1038/s41591-026-04549-6
A phase 1 trial evaluating the safety of iPSC-derived neural stem cell transplantation in subacute complete spinal cord injury, with 2–4 years of follow-up including MRI, neurological and functional assessments met its primary outcome.
A renewed push from the right against abortion pills
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Bespoke ASOs Cut Seizures, Boost Skills in Rare Epilepsy Syndrome
Two children with an ultra-rare epilepsy linked syndrome called SCN2A-developmental and epileptic encephalopathy (DEE) have been treated with personalized antisense oligonucleotide (ASO) therapies for their specific genetic mutations.
Both children, 9 and 14-year old boys, experienced significant improvements from the therapy. They both had less seizures and could cut back or stop some of the anti-seizure medications. They also achieved improvements in language and motor skills, with the older patient walking independently for the first time after being treated.
SCN2A‑DEE is a severe early‑onset epilepsy syndrome caused by pathogenic variants in the SCN2A gene, which encodes a voltage‑gated sodium channel in excitatory neurons. These variants typically lead to DEE with difficult‑to‑control seizures and profound neurodevelopmental impairment and impact around 16,000 people in the U.S.
Like many rare diseases, children with SCN2A‑DEE often have different mutations, albeit in the same gene. “The therapy is deliberately designed to target the individual’s genetic diagnosis,” said principal investigator Olivia Kim‑McManus, MD, associate professor of neurosciences at UC San Diego School of Medicine and director of the Rady Precision Therapeutics Neuro-Interventional Program at Rady Children’s Hospital San Diego, in a press statement. “The ASO modifies genetic expression and what proteins are expressed.”
This study, which is published in Nature Medicine, involved investigation, design, and treatment of the two boys in parallel. To begin with, the researchers designed allele‑selective ASOs targeting heterozygous intronic SNPs in SCN2A to suppress the mutant transcript while sparing the wild-type copy.
They then ran two parallel first‑in‑human N-of-1 trials for the two boys with individualized dosing. The primary endpoints were seizure frequency and neurodevelopment, plus phenotype‑tailored measures like impact on autism-like symptoms, movement problems, and gastrointestinal function.
Notably, the team scanned 19 infants with related SCN2A disorders and found that three of them could be eligible for treatment with the same ASO as the one given to the 14 year old boy in the future, as it is designed to treat a number of different mutations on the SCN2A gene.
Both boys had fewer seizures on the customized drug. The younger child had an estimated 26% reduction and could come off phenytoin treatment without losing overall control, while the older child’s seizures fell by about 90%, with longer seizure‑free stretches and less need for rescue medication.
Families and clinicians also saw improvements in motor function, abnormal movements, communication and gastrointestinal symptoms, and no serious safety signals emerged from the study.
“We’ve seen changes across the board, showing that targeting the root genetic cause can produce measurable improvement,” said Kim‑McManus.
One key improvement was that the older child began to walk on his own for the first time. “Since then, he’s been walking independently,” said Kim-McManus. “When we really think about precision therapy in a personalized way, you can’t get more personalized than that.”
The researchers are now hoping to use a similar approach to treat more children with SCN2A-related disorders as well as other monogenic conditions.
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High-Risk Multiple Myeloma Redefined in Era of Modern Quadruplet Therapy
Advances in frontline treatment for multiple myeloma may prompt clinicians to rethink how they identify patients with the poorest prognosis, according to a study published in Cancer. Researchers report that patients whose disease progresses within 36 months—not the longstanding 18-month benchmark—should now be considered to have functional high-risk (FHR) multiple myeloma.
Functional high-risk disease has traditionally been defined as myeloma that progresses within 18 months of starting therapy, a group historically associated with survival of less than two years after relapse. However, widespread adoption of quadruplet therapy—combining an anti-CD38 antibody, a proteasome inhibitor, an immunomodulatory agent, and dexamethasone—followed by autologous stem cell transplantation (ASCT) has substantially prolonged remission for many patients.
To determine whether the historical definition remains appropriate, investigators from the University of Alabama at Birmingham and the CoMMiT consortium analyzed outcomes in 310 patients with newly diagnosed multiple myeloma treated with quadruplet therapy plus ASCT. Patients were followed for a median of 41.8 months (3.5 years), during which 66 experienced disease progression.
The researchers evaluated several definitions of FHR disease based on progression occurring within 12, 18, 24, or 36 months after treatment initiation. Their analysis found that progression within 36 months most accurately identified patients whose survival after relapse remained approximately two years or less despite current frontline therapy.
“The current analysis provides validation of FHR36 as the optimal classification for FHR multiple myeloma in the era of QUAD + ASCT, providing a benchmark for future therapies to be explored in this setting,” the authors conclude.
Using the new definition, 16.4% of patients were classified as having FHR36 disease. Many would not have been identified as high risk using conventional staging systems: more than one-third had lower-stage disease according to the second revised International Staging System, and more than half met standard-risk criteria under current International Myeloma Society guidelines.
The study also suggests that T-cell redirecting therapies (TCRTs), including CAR T-cell therapies and bispecific antibodies, may improve outcomes in this population. Although only 11 patients received TCRTs as second-line treatment, outcomes were markedly better than with conventional therapies.
The 12-month second progression-free survival rate was 80% for patients treated with TCRTs, compared with 23% for those receiving other therapies. Overall response rates were 91% versus 47%, respectively. Multivariable analysis showed that TCRT remained associated with improved progression-free survival after adjustment for FHR status.
The authors caution that these findings require confirmation because relatively few patients received TCRTs. Still, they argue that patients meeting the FHR36 definition should be prioritized for early T-cell redirecting therapy and enrollment in clinical trials evaluating novel agents.
“We believe FHR36 should be a standard definition for FHR going forward and that the safety and efficacy of experimental agents should be reported in this important subset of patients or dedicated trials should be designed and conducted for this special population,” the authors write.
The post High-Risk Multiple Myeloma Redefined in Era of Modern Quadruplet Therapy appeared first on Inside Precision Medicine.
Patient-Derived Tumor Organoids Show Promise for Personalizing Cancer Treatment
The development of patient-derived tumor organoids for preclinical research will undoubtedly advance precision medicine research. Now, researchers have developed a pan-cancer patient-derived organoid (PDO) platform comprising 220 PDOs from 191 patients across 15 cancer types. This advance points to an increase in the use of tumor organoids as models for evaluating and optimizing cancer treatments.
This work is published in Science Advances in the paper, “Patient-derived organoids across cancers reveal conserved tumor heterogeneity and actionable therapeutic vulnerabilities.”
The team characterized the organoids extensively, showing that they retained key characteristics of the parent tumors over extended periods and showed promise in screens to identify unrecognized treatment candidates. The organoids had similarity to their parent tumors in terms of microscopic appearance, driver DNA mutations, gene expression patterns and other features.
More specifically, the comprehensive characterization demonstrated “high fidelity to parent tumors, with 93% histopathology concordance, 80% median genomic concordance for driver mutations, and a 0.85 median gene expression correlation.” Expression profiles remained largely stable over 10 passages, ensuring reproducibility for long-term screening. And clonality analysis, the authors note, showed that 85% of dominant tumor clones were preserved, with genomic concordance directly reflecting clonal similarity.
“Essentially, these organoids appear to be very good preclinical models of the parent tumor, and are practical models because they can be used long-term,” said Andrea Sboner, PhD, associate professor of pathology and laboratory medicine, director of informatics and computational biology in the Englander Institute for Precision Medicine and a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell.
The team selected a subset representing patient tumors that, based on standard clinical criteria, had been deemed ineligible for treatment with a new class of drugs—PARP inhibitors. They then tested a PARP inhibitor, talazoparib, on the organoids, and found that more than half—58%—showed substantial sensitivity, implying that the current clinical criteria are excluding patients who could benefit from such drugs. The team characterized the mutational and other features that made these organoids susceptible—offering clues to how the clinical criteria might be expanded—and identified drugs that synergistically enhance talazoparib’s effects.
“You can use these organoids as patient ‘avatars’ during clinical trials of experimental therapies, for example, to get an early picture of treatment effects and side effects,” notes Juan Miguel Mosquera, MD, a professor of pathology and laboratory medicine and director of research pathology at the Englander Institute.
The scientists also envision the future use of tumor organoid technology in selecting treatments for individual patients—growing an organoid from a sample of the patient’s tumor and then testing it rapidly with different treatment regimens.
The post Patient-Derived Tumor Organoids Show Promise for Personalizing Cancer Treatment appeared first on GEN – Genetic Engineering and Biotechnology News.
New CVD Risk Tool Boosts Women’s Risk, Lowers Risk for Some Black Adults
A change in the guidelines used to judge a person’s cardiovascular risk in the U.S. means who is classed as ‘at risk’ or not depending on their lipid levels and other factors will change.
Men, non‑Hispanic Black adults, and current smokers are more often moved down, whereas women and people with diabetes would see their risk category upgraded with the new tool suggests research led by Allison Peng, MD, Johns Hopkins University School of Medicine, and colleagues.
The research is published in JAMA and compares risk classification with the new PREVENT-atherosclerotic cardiovascular disease (ASCVD) tool and the 2013 pooled cohort equations, which have been the standard tools for estimating 10-year atherosclerotic cardiovascular disease risk for a long time.
The team used data from the National Health and Nutrition Examination Survey, a large ongoing study that interviews and examines a sample of the U.S. population every year and focused on 24,403 adults aged 40 to 79 years who did not already have cardiovascular disease and did not have very high levels of low‑density lipoprotein (LDL) cholesterol.
For each person, the investigators estimated the chance of a heart attack or stroke in the next 10 years using both the old and new calculators, grouped them as low, borderline, intermediate, or high risk under each system, and then asked who moved up or down. They also examined whether this reshuffling would change who is advised to take cholesterol‑lowering medicines such as statins.
The new tool removes race as an input, adds more risk factors such as body mass index and markers of glycemia and kidney disease, and predicts both 10‑ and 30‑year cardiovascular risk, whereas the old tool focused on 10‑year ASCVD and treated race as Black vs. White.
The results show 22% of study participants changed risk category with the new calculator. Around 14% of all adults were placed into a lower‑risk group, while about 7% were moved up. Around 50% of the population continued to be classed as low risk, but the borderline group grew from about 13% to 18%, while the intermediate group shrank from about 25% to 20%, while the high‑risk group did not change much from about 12% to 11% with the new tool.
Key changes show women’s risk increasing and men’s decreasing, factors such as diabetes playing a bigger role in risk estimation and Black adults being generally classed as lower risk.
In the older framework, an intermediate or high risk often directly triggered a statin recommendation. With the new tool, more patients sit in the enlarged borderline group and would be offered additional tests like coronary artery calcium scoring and allowed shared decision‑making about medications and preventive treatment. Despite these shifts, the proportion of adults for whom statins would be recommended was almost unchanged at around 50% before and after.
“Overall, cardiovascular risk reclassification with the 2026…Dyslipidemia Guideline may result in opportunities for consideration of more personalized cardiovascular risk assessment with risk enhancers and coronary artery calcium scoring to guide lipid-lowering therapy and cardiovascular disease prevention,” write the authors.
In an accompanying editorial in the same journal, Philip Greenland, MD, Northwestern University Feinberg School of Medicine, and Karen Lasser, MD, Boston Medical Center, Boston University, note that despite improving risk assessments, many people who are at risk still do not get treatment or reach suggested goals for healthy cholesterol levels.
“A large percentage of U.S. adults aged 30 years or older are candidates for guideline-directed lipid lowering therapy, and many who are currently taking lipid lowering therapy are not reaching new (or previous) low density lipoprotein cholesterol goals. This is a huge public health burden for the U.S. population for a medical condition that should be highly treatable.”
They conclude: “Given the large numbers of people who would be recommended for treatment following a risk-based discussion, these reports signify a major challenge, and so far, a missed opportunity, for the U.S. health care system.”
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