Wiping out zombie-like brain cells that are worn out but won鈥檛 kill themselves could provide a new way to prevent or treat Alzheimer鈥檚 disease and other types of dementia. That鈥檚 the conclusion of experiments in mice showing that if these 鈥榮enescent鈥� cells are eradicated as they develop through life, the brain is protected against further degeneration.

鈥淲e show that senescent cells promote neurodegeneration and cognitive loss,鈥� says Darren Baker of the Mayo Clinic in Rochester, Minnesota, and head of the team. 鈥淧reventing these cells from accumulating attenuates disease.鈥�

Baker studied mice genetically engineered so that their brains degenerate unusually early in life by becoming clogged with damaging clumps of fibres called tau tangles. His team discovered that by the time the mice were a year old, they had also over-accumulated senescent cells. Compared with healthy control mice, they had a dozen times as many senescent cells in the brain鈥檚 memory centre 鈥� the hippocampus 鈥� and twice as many in the cortex, the 鈥渢hinking鈥� hub of the brain.

Cell destroyer

To find out if senescent cells also drive the tau-related brain degeneration, the researchers crossed the tau tangle-prone mice with mice whose senescent cells could be selectively destroyed as they emerged throughout life by treating the mice with a drug called AP. Destroying the senescent cells halted brain degeneration in the tau tangle-prone mice, and prevented their usual loss of memory and cognitive ability.

鈥淭his is exciting,鈥� says Aubrey de Grey, a co-founder of the SENS Research Foundation in Mountain View, California. 鈥淪everal years of work pioneered by Baker and his colleagues has shown overwhelmingly that senescent cells make far broader contributions to the health problems of old age than we might previously have expected.鈥�

Earlier this year, another team at Mayo showed they could increase by 36 per cent the lifespan of elderly mice by giving them a drug combination 鈥� including one derived from apple peel 鈥� that destroys senescent cells.

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People with cocaine addiction may soon be invited to test a pioneering new treatment that destroys the cocaine they take before it can hit the reward centres in their brain, using genetically engineered versions of their own skin cells.

Currently, there are and many who do successfully kick the habit will ultimately relapse. Approximately from cocaine overdoses.

The new therapy might help tackle the problem. Skin cells would be taken from recipients and equipped in the lab with an extra gene that constantly makes human butyrylcholinesterase (hBChE), an enzyme that rapidly destroys cocaine in the bloodstream. Then the cells would be multiplied into a clump called an organoid that doctors would implant permanently under the recipient鈥檚 skin.

Ming Xu at the University of Chicago in Illinois and his colleagues have trialled the therapy in mice. Xu鈥檚 team鈥檚 results show that the prototype strategy worked exactly as hoped. Within 20 minutes, six mice with an active implant had practically eliminated a standard dose of cocaine injected into their tummies, a job that took six control mice almost 2 hours. And unlike the control mice, the treated mice didn鈥檛 get a 鈥減leasure hit鈥� in the brain from the neurotransmitter, dopamine.

This absence of a 鈥渉it鈥� also meant that unlike the controls, the treated mice didn鈥檛 go searching for more cocaine in standard tests to measure this behaviour, and didn鈥檛 preferentially visit previous sites where cocaine was accessible. They did, however, seek out more alcohol when it was made available to them, demonstrating that the treatment specifically targets cocaine addiction.

No cocaine-induced relapses

Xu expects the treatment would be effective in people too. 鈥淚t will work, like in mice, by highly efficiently degrading cocaine as soon as it enters the blood circulation so that little would reach the brain,鈥� he says.

鈥淧eople addicted to cocaine would stop using it, and there would be no cocaine-induced relapses,鈥� says Xu. 鈥淭here are no methods approved by the US Food and Drug Administration for treating cocaine abuse, so it could be the first.鈥�

Almost all treated mice also survived huge doses of cocaine that killed controls. Xu gave treated and control animals doses of 40, 80, 120 and 160 milligrams of cocaine per kilo of body weight. All control animals died on the largest two doses, and half the controls on the 80-milligram dose.

Xu鈥檚 team also tested prototype human versions of the organoids, made from foreskin cells of newborn baby boys. Like the mouse organoids, they produced the necessary enzyme continuously, for at least two months. 鈥淲e鈥檇 like to move to clinical trials as soon as possible,鈥� he says.

Encouragingly, Xu says that some of the mice originally treated are still healthy, with active organoids, after six months, providing hope the treatment will be long-lasting in patients. He also says that similar grafts of patients鈥� own skin have been used without complications for decades to treat conditions such as burns and other skin disorders, which suggests the organoids wouldn鈥檛 be rejected.

鈥淚 would expect this medication could prove effective when partnered with cognitive behavioural therapy to help people interpret and better cope with distressing cocaine craving,鈥� says John Marsden, professor of addiction psychology at London鈥檚 Institute of Psychiatry. 鈥淚t鈥檚 very encouraging that research in the US remains undaunted by the stubbornness of cocaine use disorder to respond to treatment, and I remain optimistic we鈥檒l see an evidence-based medication.鈥�