Health
Organ Rejection Drug Beats Standard Kidney Transplant Treatment
We also report on potentially important discoveries that could lead to the first treatment for West Nile virus, and improved care of pneumonia patients.
A NEW IMMUNOSUPPRESSANT FOR KIDNEY RECIPIENTS
An experimental immunosuppressant drug being developed by Eledon Pharmaceuticals (ELDN.O), opens new tab proved superior to the current standard treatment, according to data from a clinical trial, and looks to be a potential game-changer for kidney transplant patients.
Kidney recipients must take immunosuppressive drugs for their lifetime to prevent organ rejection. The medications can affect both long-term graft survival and how patients feel and function in their daily lives.
While the current standard-of-care immunosuppressant – tacrolimus, in use since the 1990s – basically affects the entire immune system, the Eledon drug, tegoprubart, selectively blocks the activation of specific immune cells in the so-called CD40L pathway.
In a long-term follow-up study of kidney transplant patients who participated in a 12-month mid-stage trial, those treated with tegoprubart had superior kidney function from one month onward compared with patients treated with tacrolimus, researchers reported at the American Transplant Congress, opens new tab in Boston.
Patients treated with tegoprubart had no graft loss and no biopsy-proven acute rejection episodes after the first six months post-transplant, compared with roughly 64% in the tacrolimus group.
Side effects were less common with tegoprubart as well. Just 2% of those who got the Eledon drug experienced headache or acute kidney injury versus 12% and 6% for tacrolimus, respectively. None of the patients taking the new drug had extremity pain, or falls or loss of balance, compared with 10% and 6% for the standard of care.
“For kidney transplant recipients, success is measured not only by preventing rejection, but by preserving kidney function and maintaining quality of life over the long term,” study leader Dr. Andrew Adams of the University of Minnesota said in a statement.
Eledon has said it plans to conduct a late-stage trial of tegoprubart in kidney recipients later this year.
In a separate presentation at the meeting, Dr. Nicole Wojcik from the University of Chicago reported on a pilot study in which tegoprubart was well-tolerated and effective in patients with diabetes undergoing pancreatic islet cell transplantation.
DEVELOPING PROTECTION AGAINST THE WEST NILE VIRUS
Researchers have identified antibodies that could lead to development of a vaccine or a treatment for West Nile virus, the mosquito-transmitted disease that can cause severe brain infection and death.
Studying blood samples provided by survivors of the disease, the researchers found the antibodies that may help address this unmet medical need, according to a report published in Immunity, opens new tab.
Reproducing the antibodies in test tubes, they found that one, called W010, recognizes and attacks a protein on the virus envelope that helps it attach to and infect host cells.
Treatment with W010 protected mice when administered before and even five days after exposure to West Nile virus.
A second antibody, W014, was effective not only against West Nile virus but also against other orthoflaviviruses, including Japanese encephalitis, Murray Valley encephalitis, Saint Louis encephalitis and Usutu viruses.
The identification of these human antibodies – and the vulnerable sites they target on the viruses – will help guide “the development of medical countermeasures against severe diseases that… represent an important unmet medical need globally,” the researchers said.
PNEUMONIA DISCOVERY MAY IMPROVE TREATMENT OF SEVERE CASES
Severe pneumonia has three distinct subtypes with varying biological responses, a finding that helps explain why some patients recover quickly while in others the lung infection becomes fatal, researchers say.
On the surface, the 95 intensive-care-unit patients in the study appeared similarly ill, but their outcomes were very different, study leader Dr. Mark Jeffrey of the University of Cambridge said in a statement.
“It was only when we drilled down and looked at patterns of inflammation that the differences became apparent,” he said.
About half the patients mainly had immune-system suppression, significant damage to the lining of the lungs, and bleeding in the tiny air sacs in the lungs. These patients did not have many signs of inflammation, which may explain why anti-inflammatory medications can fail or even be harmful in some cases, the researchers reported in Nature Communications, opens new tab.
Another quarter of patients – those who were critically ill for the longest periods and spent the most time on mechanical ventilation – had severe and persistent inflammation, with a flood of immature immune cells in the lungs. They would be most likely to respond to anti-inflammatory treatments, the researchers said.
Finally, about a quarter of cases were characterized by a balanced immune response and active repair of damage to the lungs. These patients were most likely to recover faster and spend the shortest time on the ventilator, even though they initially appeared to be just as ill as the others.
“This helps explain why ‘one-size-fits-all’ treatments, including some immune-modulating drugs, have often failed in clinical trials,” Jeffrey said.
Senior study author Dr. Andrew Conway Morris of the University of Cambridge said failing to look at the disease’s underlying biology risks missing important information.
“Instead of asking ‘Does this patient have pneumonia?’, we should be asking ‘What’s the inflammatory pattern in this patient’s lungs?’” Morris said.
Study coauthor Dr. Vilas Navapurkar from Addenbrooke’s Hospital in Cambridge added, “If we know which subtype of pneumonia an individual has, we can potentially tailor their treatment more precisely, boosting the immune response in some, while calming harmful inflammation in others.”
REUTERS
Health
Definium Depression Pill Delivers Strong Trial Results, Shares Surge
Definium Therapeutics (DFTX.O), opens new tab said a single dose of its LSD-based experimental pill significantly reduced symptoms of major depression in patients in a late-stage trial, sending its shares soaring 55% to a more than four-year high on Monday.
The experimental drug helped patients record significantly lower scores on a standard depression scale than those on placebo after six weeks, with an 8.1-point difference, meeting the trial’s main goal, the company said.
The pill, DT120, belongs to a class of drugs known as classic psychedelics, which temporarily alter perception, mood and thinking. It is a pharmaceutical formulation of lysergide, better known as LSD, and works by activating serotonin receptors in the brain.
In April, U.S. President Donald Trump signed an executive order to speed up access to psychedelic-based treatments.
Definium shares, which have gained about 174% so far this year, were trading up 52% at $37.23.
Needham analyst Ami Fadia called the results “unprecedented in the depression space,” adding the drug showed greater reductions in scores at six weeks than Johnson & Johnson’s (JNJ.N), opens new tab Spravato and Compass Pathways’ (CMPS.O), opens new tab COMP360 achieved at week four.
Axsome Therapeutics’ (AXSM.O), opens new tab Auvelity and Sage Therapeutics’ Zurzuvae are some of the other treatments for major depressive disorder (MDD).
“DT120 could emerge as a worthy competitor in the MDD / TRD space with a strong clinical profile,” Fadia added.
Definium said the data brings it closer to an FDA submission and it was running a second late-stage depression trial.
The drug was generally well-tolerated, with 99% of adverse events mild to moderate, occurring mainly on the day of dosing, and no serious safety issues or increase in suicidal thoughts observed.
The trial enrolled 149 participants aged 18-74 years with MDD, the second-most common mental health disorder in the U.S., with more than 21 million adults experiencing a major depressive episode each year.
Reuters
Health
PCOS: Matter Of Eggs And Far Beyond
Dr. Pooja Vaswani – Consultant Obstetrics & Gynaecology.
NMC Royal Hospital, Abu Dhabi
Quite many times in our daily practice we come across women who are diagnosed to have Polycystic Ovarian Syndrome (PCOS), the incidence of which is on an increase. It affects about 10% of women. It’s the word “PCOS” that catches any woman’s attention, as more often than not she would have heard about PCOS from her friends/ mother or sisters. Immediate question that comes to the mind of the woman is “will I be able to conceive?”
Ofcourse maternal instinct is paramount and being a gynecologist women with PCOS come to me with concerns that are either cosmetic or reproductive. As gynecologist we cater to reproductive goal,however it is to be kept in mind that as a doctor our role does not end there. PCOS has long term implications too which can go far beyond the reproductive age.Many studies confirm that the insulin resistance associated with PCOS can expose women to higher risk of metabolic syndrome which could be a combination of hypertension; hyperlipidemia, diabetes and cardiovascular disease.
Apart from these metabolic disorders, women with PCOS are also at an increased risk of developing endometrial, ovarian and possibly also breast cancer in later life.
There is a need for a holistic approach in dealing with PCOS keeping in mind that contrary to what the name implies, PCOS implications are not restricted just to sex organs but go way beyond, affecting many other organs in the body which can have profound effect on long term health of the women. These women should be evaluated for these conditions accordingly on a more frequent basis.
Every responsible gynecologist should utilize every potential opportunity to evaluate and educate the patients about ways to prevent these potentially threatening long term metabolic and malignant disorders by intervening at the earliest.
Health
Novartis: Rare muscle disease drug shows early promise
Novartis (NOVN.S), opens new tab said on Thursday an experimental drug, which it acquired as part of its $12 billion takeover of Avidity, showed promise in an early-to-mid-stage study in patients with a type of genetic muscle disorder characterized by slowly progressive muscle weakness.
- The Swiss drugmaker said the drug, known as del-brax, lowered two blood markers linked to the disease and showed reduced signs of muscle damage in patients with facioscapulohumeral muscular dystrophy.
- Novartis said the drug shows potential to become the first disease-modifying treatment for FSHD, which can cause weakness in the face, shoulders, arms and other muscles.
- The company estimates it affects about 45,000 to 87,000 people in the U.S. and EU.
- The drug’s safety profile was consistent with previous results, the company said.
- Novartis plans to discuss the data with health regulators around the world, while a late-stage study of the drug is currently enrolling patients.
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