Strategies for crossing blood-brain barrier in Parkinson’s are promising
Researchers review developing approaches now being tested
Several promising strategies for developing therapeutics capable of crossing or bypassing the blood-brain barrier (BBB) offer potential for treating neurological conditions like Parkinson’s disease, but more work is needed to establish their benefits in clinical trials, a review study suggests.
Strategies such as direct brain delivery, focused ultrasound, and nanotherapeutics are all being explored as ways around the BBB, a tightly linked layer of cells that line the brain’s blood vessels and help defend it against potentially harmful substances circulating in the body. It’s what helps keep things like toxins, pathogens, or inflammatory immune cells from accessing brain tissue and damaging it.
The membrane also hinders the ability of medications to access brain tissue and has proven a major hindrance toward developing therapies for neurological diseases like Parkinson’s.
“The blood-brain barrier has long been a bottleneck in treating neurological diseases,” David Dickens, PhD, a lecturer at the University of Liverpool in England and the study’s senior author, said in a university news story. “These cutting-edge approaches are enabling us to bring treatments directly to the brain, improving efficacy and reducing risks.”
The strategies are also being tested in other neurological conditions, including Alzheimer’s disease, amyotrophic lateral sclerosis, and glioma, a type of brain tumor.
The study, “Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease,” was published in The Lancet Neurology.
When given systemically, such as via a pill or injection into the bloodstream, virtually all large molecule medications and most small molecules aren’t able to cross over the selective barrier and act in brain tissue, which limits their efficacy at treating neurological conditions.
Further complicating the matter is that the BBB becomes altered in many neurological diseases, including Parkinson’s, which can influence how different therapeutics behave at different stages of disease.
Getting into or around the BBB
A focus of research in recent years has been to find ways to overcome these challenges to enable effective therapeutic delivery to the brain. In their report, the team of scientists reviewed the most promising strategies that have been published on the topic.
Among the approaches that have been tested in Parkinson’s patients is direct brain delivery, where the BBB is bypassed entirely by administering treatments directly into brain tissue.
The researchers pointed toward the investigational Parkinson’s therapy bemdaneprocel, which involves surgically implanting dopamine-producing stem cells into the brain. Dopamine is the brain signaling chemical that’s lost in Parkinson’s due to the degeneration of the nerve cells that produce it.
Bemdaneprocel is moving into a Phase 3 study this year after having been found safe and effective in a small Phase 1 trial (NCT04802733).
Another approach gaining traction is ultrasound technology, where focused sound waves are combined with tiny bubbles injected into the bloodstream to temporarily open the BBB and allow medications access. An ultrasound approach was found safe and feasible in a small clinical trial of Parkinson’s patients.
Also being investigated are targeted approaches that leverage natural transport systems in the body to aid the movement of medications across the BBB. This has been tested in forms of brain cancer, according to the review.
Finally, the scientists discussed nanotherapeutics, where tiny carrier molecules, or nanoparticles, with properties that enable them to cross the BBB are used to package medications and carry them into the brain. Nanoparticles can also be engineered to have therapeutic properties.
A variety of nanoparticle-based approaches have been tested in preclinical Parkinson’s studies where they’ve shown various benefits, but the approach is still in early stages, according to the authors.
Overall, “these breakthroughs could transform the way we treat brain diseases, offering new hope to millions of patients worldwide,” Dickens said.
The scientists said each approach has its own benefits and drawbacks, and may have different applications.
“No singular method of crossing the blood–brain barrier will likely be appropriate for the various neurological disorders, or even for individuals with the same disease,” the researchers wrote.
For people with Parkinson’s, where there are available therapies to ease symptoms, some patients might not want to risk more invasive approaches such as brain injections. On the other hand, people with a poor prognosis and fewer treatment options, such as in certain brain cancers, may find such risks more acceptable, said the researchers, who emphasized that the strategies they reviewed are still “in their infancy” and that “robust clinical trial data will be required to establish their role in routine clinical practice.”
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