Ageing Brain Blocks Alzheimer’s Drugs, Review Warns
A BITS Pilani researcher’s review finds that ageing-related changes in the brain may limit how effectively nanoparticle-based medicines reach their targets.
Getting a medicine across the blood-brain barrier may not be enough to treat diseases of the ageing brain, with changes in blood vessels, waste clearance and immune activity potentially affecting whether the drug reaches its intended target, a new review involving a BITS researcher has found.
The review, published in Ageing Research Reviews, examines how ageing changes the environment inside the brain and, in turn, the behaviour of nanoparticles used to carry medicines. It argues that drug-delivery systems designed and tested mainly in young, healthy brains may not perform in the same way in older people.
Dr Rajeev Taliyan of the Neuropsychopharmacology Division, Department of Pharmacy, BITS Pilani, is among the authors of the review, along with researchers from Taipei Medical University and affiliated institutions in Taiwan. The other authors are Ruei-Dun Teng, Jui-Ming Sun, Ting-Lin Yen, Cheng-Ta Hsieh and Chih-Hao Yang.
“Crossing the blood-brain barrier is only the first step in delivering medicines to the brain. As we age, the brain undergoes several changes that can affect how a medicine reaches its target and how well it works,” Dr Taliyan said.
The blood-brain barrier acts as a protective filter between the bloodstream and brain, making it difficult for many medicines to enter. But the review says the challenge continues even after a drug-carrying nanoparticle gets through. Ageing can stiffen blood vessels, reduce blood flow and impair the brain’s glymphatic waste-clearance system, while chronic immune activation can influence how nanoparticles are distributed, retained and cleared.
The authors therefore call for age-responsive drug-delivery systems that account for the changing conditions inside an older brain. These could include nanoparticles that release medicines in response to specific biochemical signals, as well as dosing strategies that take the body’s daily biological rhythms into account.
They also call for more realistic preclinical testing, including age-specific assessment of nanoparticle behaviour, safety and patient characteristics, before such systems are taken towards clinical use. The approach could be relevant to developing treatments for age-related neurological conditions such as Alzheimer’s and Parkinson’s disease, although the review does not present a new treatment for either condition.