Health Rounds: Blood-brain barrier discovery could lead to new Alzheimer’s disease approach

(This is an excerpt of the Health Rounds newsletter, where we present latest medical studies on Tuesdays and Thursdays.) By Nancy Lapid Nov 13 (Reuters) – Today we feature an exciting discovery about how the blood-brain barrier allows beneficial proteins to reach the brain, which could lead to new therapeutic approaches. We also cover a small trial that could be very good news for people with diabetic foot ulcers that won’t heal, and a cautionary study for pregnant women who may be exposed to wildfire smoke. THE BLOOD-BRAIN ​BARRIER IS ACTUALLY A FILTER The network of blood vessel cells that serves as a border between the brain and the rest of the bloodstream is a sophisticated filter that ‌lets helpful proteins pass through to the brain, a discovery researchers said could lead to a novel approach to treating Alzheimer’s and other diseases. “For a century, we’ve treated the blood-brain barrier as a simple physical boundary protecting the brain from toxins,” study leader Andrew Yang of the Gladstone Institutes in San Francisco said in a statement. “We’re finding that it’s an intelligent interface that plucks the right proteins in the blood, often from distant parts of the body, and delivers them to the right cell types in the brain.” Working in mice, the researchers used protein-labeling chemistry to tag 861 mouse blood proteins that were re-injected into the bloodstream. Brain tissue analyses showed 92 had been allowed to cross the ‌blood-brain ​barrier. Once inside the brain, different proteins were directed to specific types of brain cells, researchers reported in Cell. Most of the proteins that ⁠got past the barrier were produced in distant parts of ⁠the body. For example, the liver protein apolipoprotein A1 travels to the brain to help maintain healthy connections between neurons, a discovery that could lead to new treatments for Alzheimer’s disease, the researchers said. “Alzheimer’s disease may not start entirely inside the brain. It may start when the brain’s supply line from the body is severed,” Yang said. “If that’s right, we may be able to fight this disease from outside the brain, by restoring what the brain has lost.” Studying mice with a form of Alzheimer’s, they found that if the blood-brain barrier stops importing ​APOA1 into the brain, the reduced supply leads to an erosion of neuronal connections, behavioral changes, and other early signs of the disease. When the researchers studied mice that were genetically engineered to produce extra APOA1 in the liver, more APOA1 crossed the blood-brain barrier and entered the brain and the mice showed fewer signs of Alzheimer’s disease. “We now have a map of the proteins the ⁠brain needs from the body and the transport system that delivers them,” Yang added. “We are excited to translate this blueprint ⁠into new therapies for Alzheimer’s that work from the outside-in, and into next-generation blood-brain barrier shuttles to deliver powerful medicines into the brain.” PLACENTAL STEM ​CELLS SHOW PROMISE FOR DIABETIC FOOT ULCERS In a first-in-human trial, a therapy derived from human placentas healed chronic diabetic foot wounds that had not responded to standard treatments, researchers say. Diabetic foot ulcers are open ​wounds that develop when diabetes damages the nerves that allow a person to feel injuries to the foot along with the arteries that carry blood necessary ‌to facilitate healing. Up to 20% of patients with chronic diabetic foot ulcers eventually require an amputation, according to the American Diabetes Association. The 10 study participants had “substantial” wounds, according to a report in Stem Cells Translational Medicine. Each received a single treatment of investigational cells derived from healthy placental tissue that’s usually discarded following childbirth. The cells were injected into and around the wound and into nearby soft tissue. Two participants saw their wounds heal within two months, and all 10 had complete wound closure within six months. “This early study was designed foremost to answer a safety question,” study coauthor Dr. Michael Carstens of the ⁠Wake Forest Institute for Regenerative Medicine in North Carolina said in a statement. The cells were well tolerated, and there were no treatment-related serious adverse events during the 12 months of follow-up, he said. Nine of the 10 patients also had improved sensation in the treated feet during the 12-month follow-up period, which suggests the placental stem cells might eventually be useful not just for healing diabetic foot ⁠ulcers but also for treating some forms of the nerve disorder known as ‌peripheral neuropathy, the researchers said. WILDFIRE SMOKE IN UTERO LINKED WITH CHILDHOOD ASTHMA Children whose mothers inhaled wildfire smoke and other air pollution during the ⁠middle and later months of pregnancy were more likely to develop asthma, California researchers reported at the American College of Allergy, Asthma and ​Immunology annual meeting in ‌Phoenix. “A baby’s lung development begins before birth, and our study suggests that certain stages of pregnancy maybe be especially vulnerable to the ​effects of wildfire smoke,” ⁠study leader Dr. Anh Nguyen of the UC Davis Medical Center in Sacramento said in a statement. The researchers studied 1,097 children born full-term to mothers who were pregnant during the 2017–2020 Northern California wildfires. Asthma in early childhood was linked to higher exposure to fine-particle air pollution in general during the second trimester and to wildfire pollution during the third trimester, they found. The study does not prove smoke causes asthma. Still, knowing which months of pregnancy may matter most could help doctors offer pregnant women clearer advice during wildfire season, the researchers said. “Pregnant women can’t control when a wildfire happens, but there are things they can do on smoky days,” Nguyen said. “Staying indoors, keeping windows closed, and using an air purifier can help lower how much smoke they breathe in.” (To receive the full newsletter in your inbox for free sign up ​here) (Reporting by Nancy Lapid; Editing by Bill Berkrot)