FDA Approves Zycubo (copper histidinate) for Children With Menkes Disease

Sentynl Therapeutics Inc. (“Sentynl”), a U.S.-based biopharmaceutical company wholly-owned by Zydus Lifesciences Limited (“Zydus Group”), announced that the U.S. Food and Drug Administration (“FDA”) has approved Zycubo® (copper histidinate) for the treatment of Menkes disease in pediatric patients. This is the first and only treatment approved for Menkes disease, a rare and fatal genetic condition, in the United States. Zycubo® is not indicated for the treatment of Occipital Horn Syndrome.

“Approval is a pivotal step towards achieving our goal of making a meaningful impact on patients, caregivers, and the rare disease community,” said Dr. Sharvil P. Patel, Managing Director, Zydus Lifesciences Limited. “This milestone marks a transformative moment for the Zydus Group and for families affected by Menkes disease. For the first time, patients have access to an approved therapy, offering hope where no options existed. We are proud to advance patient care and deliver innovative solutions to those who need them most.”

Menkes disease is a rare X-linked recessive pediatric disease caused by mutations of the copper transporter ATP7A encoded by the ATP7A gene. Patients with Menkes disease are born with the inability to absorb dietary copper and subsequently have impaired copper transport across the blood-brain barrier, and, until now, there has been no approved treatment in the United States. Zycubo® is a subcutaneous injectable formulation of copper histidinate that restores copper homeostasis and maintains copper levels in patients with Menkes disease.

“Menkes disease presents significant challenges for patients and their families. With no known cure, most untreated patients do not survive beyond three years of age,” said Matt Heck, CEO, Sentynl. “FDA’s approval serves as compelling affirmation that a safe and effective therapy is now available for patients living with this devastating disease.”

The approval is supported by positive topline clinical efficacy results for Zycubo, demonstrating statistically significant improvement in overall survival for Menkes disease subjects who received early treatment (“ET”) with Zycubo, compared to an untreated contemporaneous external control cohort, with a nearly 80% reduction in the risk of death. Median overall survival (“OS”) was 177.1 months for Zycubo ET cohort compared to 17.6 months for the untreated contemporaneous external control cohort.

The most common adverse reactions (incidence ≥7%) were pneumonia, viral infection, respiratory failure, seizure, bacterial infection, hemorrhage, hypotension, vomiting, tachycardia, pyrexia, volume depletion, fracture, dyspnea, transaminases elevation, diarrhea, fungal infection, anemia, and local administration reaction.

“This milestone represents the culmination of decades of research into better understanding and ultimately finding an effective treatment for Menkes disease,” said Dr. Stephen Kaler, a clinical genetics and genomics specialist at the Columbia University Medical Center. “Increased awareness of Menkes disease and rapid testing upon suspicion are critical, as beginning copper histidinate therapy in affected neonates has been shown to reduce symptoms and prolong life.”

Acquired from Cyprium Therapeutics in 2023, Sentynl has advanced Zycubo through the final stages of development with the FDA based on positive results from pivotal studies, receiving Breakthrough Therapy, Fast Track, Rare Pediatric Disease, and the FDA Orphan Drug Designations. Copper histidinate has also been granted Orphan Designation by the European Medicines Agency.

FDA Approves Zycubo (copper histidinate) for Children With Menkes Disease

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

In continuation of my update on Polyphenol-rich diets

 People who regularly consume polyphenol-rich foods and drinks, such as tea, coffee, berries, cocoa, nuts, whole grains and olive oil, may have better long-term heart health

The research, led by King's College London, found that those with higher adherence to polyphenol-rich dietary patterns had lower predicted cardiovascular disease (CVD) risk.

Polyphenols are natural compounds found in plants that are linked to various health benefits, including improved heart, brain, and gut health.

The study, published today in BMC Medicine, followed more than 3,100 adults from the TwinsUK cohort for over a decade, found that diets rich in specific groups of polyphenols were linked to healthier blood pressure and cholesterol profiles, contributing to lower CVD risk scores.

For the first time, the researchers also analyzed a large number of metabolites in the urine that are produced when the body breaks down polyphenols.

These biomarkers confirmed that individuals with higher levels of polyphenol metabolites—especially those derived from specific groups of polyphenols, flavonoids and phenolic acids—had lower cardiovascular risk scores. They also had increased HDL cholesterol, also know as "good" cholesterol.

The study used a newly developed polyphenol dietary score (PPS) to capture intake of 20 key polyphenol-rich foods commonly consumed in the U.K., ranging from tea and coffee to berries, olive oil, nuts, and whole grains.

This score showed stronger associations with cardiovascular health than estimates of total polyphenol intake, likely because it captures overall dietary patterns rather than individual compounds. This finding suggests that considering the whole diet provides a more accurate picture of how polyphenol-rich foods work together to support long-term heart health

Professor Ana Rodriguez-Mateos, senior author and Professor of Human Nutrition at King's College London, said, "Our findings show that long-term adherence to polyphenol-rich diets can substantially slow the rise in cardiovascular risk as people age. Even small, sustained shifts towards foods like berries, tea, coffee, nuts, and whole grains may help protect the heart over time."

Dr. Yong Li, first author of the study, added, "This research provides strong evidence that regularly including polyphenol-rich foods in your diet is a simple and effective way to support heart health. These plant compounds are widely available in everyday foods, making this a practical strategy for most people."

The researchers note that while cardiovascular risk naturally increases with age, higher polyphenol intake was associated with a slower progression of risk over the 11-year follow-up period. They also emphasize the need for future dietary intervention studies to further validate these associations.

Polyphenol-rich diets associated with lower long-term cardiovascular disease risk

Daily coffee drinking may slow biological aging of people with major mental illness

In continuation of my update on coffee

Drinking a maximum of 3–4 cups of coffee a day may slow the "biological" aging of people with severe mental illness, by lengthening their telomeres—indicators of cellular aging—and giving them the equivalent of 5 extra biological years, compared with non-coffee drinkers, finds research published in BMJ Mental Health.

But no such effects were observed beyond this quota, which is the maximum daily intake recommended by several international health authorities, including the NHS and the US Food and Drug Administration.

Telomeres sit at the end of chromosomes and perform a role similar to the plastic tips on the end of shoelaces. While telomere shortening is a natural part of the aging process, it seems to be accelerated in those with major psychiatric disorders, such as psychosis, schizophrenia, and bipolar disorder, note the researchers.

Study details and participant information

Telomeres are sensitive to environmental factors, including, possibly, diet. And coffee, when drunk in moderation, has been associated with various health benefits, prompting the researchers to explore whether it might influence the rate at which telomeres shorten in people with major mental ill health.

They included 436 adult participants from the Norwegian Thematically Organized Psychosis (TOP) study, recruited between 2007 and 2018: 259 had schizophrenia; the rest (177) had affective disorders, including bipolar disorder and major depressive disorder with psychosis.

Participants were asked how much coffee they drank every day and were grouped into four categories: zero (44); 1–2 cups; 3–4 cups (110); and 5 or more cups. And they were asked whether they smoked, and if so, for how long they had done so.

Participants who drank 5+ cups a day were significantly older than those who drank none or 1–2 cups a day. And those with schizophrenia drank significantly more coffee than those with an affective disorder.

Coffee intake is associated with telomere length in severe mental disorders, BMJ Mental Health (2025). DOI: 10.1136/bmjment-2025-301700

Daily coffee drinking may slow biological aging of people with major mental illness