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New trial of promising stem cell therapy for post-stroke brain recovery

A promising treatment offers hope in potentially reversing the long-term effects of stroke.

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Hiroshima University (HU) has started a human trial for a promising treatment that offers hope in potentially reversing paralysis and language disorder after moderate to severe stroke.

The proposed therapy uses patients’ own cultured MSCs (mesenchymal stem cells) taken from their cranial bone, known as autologous cranial bone-derived MSCs, as a treatment for moderate to severe cerebral infarction — from which neurological dysfunction recovery is extremely difficult with standard treatment. 

Cerebral infarction, which clinically manifests as ischemic stroke, happens when blood and oxygen supply to the brain is disrupted, most commonly due to a blood clot blocking blood vessels.

A stroke can cause a build-up in intracranial pressure that may lead to lasting brain injury or even death.

In such an urgent situation, neurosurgeons have long performed extracranial decompression, reducing the increased pressure by removing a large area of the skull and replacing the dura mater with a substitute membrane, such as a periosteum or artificial dura mater.

However, in patients with moderate to severe stroke, even if the surgery saves their lives, it could not repair the damage inflicted by the life-threatening condition on their brain tissues.

Many moderate to severe stroke patients, whose brain pressure could not be controlled without removing the skull, end up with severe residual disabilities and require assistance and care in their daily lives.

Some of the effects of stroke include paralysis, speech impairment, cognitive decline, dysphagia or difficulty in swallowing, spasticity or muscle stiffness, depression, Parkinson’s syndrome, symptomatic epilepsy, and urinary disorders. Currently, stroke has no established treatment after the recovery period.

The HU researchers leading the clinical study — Department of Neurosurgery’s Professor Nobutaka Horie and Assistant Professor Takafumi Mitsuhara and Bio-Environmental Adaptation Sciences Professor Rui Yuge, have been studying the use of MSCs for nerve regeneration therapy.

They have successfully demonstrated that cranial bone-derived MSCs effectively restored neurological function in rat models of brain infarction and spinal cord injury.

A 2007 survey on living conditions by Japan’s Ministry of Health, Labour and Welfare showed that stroke was the top two cause of dementia and the need for nursing care in the nation and the leading reason behind becoming bedridden. 

Annually, medical expenses for stroke across Japan amount to approximately 1.8 trillion yen, while nursing care reaches an estimated 1.9 trillion yen in costs.

The novel stem cell treatment can offer hope for patients wanting to revert to how their body was pre-stroke, especially since, according to the researchers, stroke cases in Japan are expected to more than double from 1.3 million in 2019 to three million in 2025 as the population ages.

MSCs, which are multipotent and capable of developing specific kinds of cells, can be obtained from different sources, but their characteristics may vary depending on the tissue of origin. 

The researchers said that cranial bone-derived MSCs are superior to the ones isolated from the iliac bone, the most exploited source of MSCs, as they possess greater expression of neurotrophic factors, neuroprotective effects of culture supernatant, and the ability to differentiate into nerves.

A previous study using a rat model of cerebral infarction also showed that MSCs derived from rat and human cranial bones proved to be abundant with neurotrophic factors, proteins that strengthen neuron health and functional recovery.

In the proposed treatment, the cells are cultured for four to six weeks. About 100 million cells per patient are prepared for intravenous administration two to three months after the onset of cerebral infarction. The autologous cranial bone-derived MSCs are intravenously injected in the subacute stage to examine the safety and efficacy of the treatment. The target number of patients for the clinical trial is six.

The first patient in the trial received the initial intravenous dose of MSCs in August.

The clinical trial is now at Phase 1 and 2a stages of testing. It is being conducted by the HUMAN (Hiroshima University Mesenchymal stem cell Application for Neuro-regeneration) Project, a collaboration among HU’s Departments of Neurosurgery and Bio-Environmental Adaptation Sciences and HU-originated venture companies TWOCELLS Co., Ltd. and Space Bio-Laboratories Co., Ltd. 

The study period for the clinical trial is until 31 December, 2023.

 

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Two teas or coffees a day could lower dementia risk, experts say

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People who drink two to three cups of coffee or tea daily have a lower dementia risk, new research suggests.

Health records for more than 130,000 people showed that over 40 years, those who routinely drank two to three cups of caffeinated coffee or one to two cups of caffeinated tea daily had a 15 to 20 per cent lower risk compared with those who went without.

The caffeinated coffee drinkers also reported slightly less cognitive decline, a measure of how thinking and memory deteriorate over time, than those who opted for decaf and performed better on some objective tests of brain function.

The findings suggest habitual tea and coffee drinking may be good for the brain, but the research cannot prove it, as caffeine drinkers may be less prone to dementia for other reasons.

The study was led by Yu Zhang, who studies nutritional epidemiology at Harvard University.

A similar link would arise if poor sleepers, who appear to have a greater risk of cognitive decline, steered clear of caffeine to get a better night’s rest.

“Our study alone can’t prove causality, but to our knowledge, it is the best evidence to date looking at coffee and tea intake and cognitive health, and it is consistent with plausible biology,” Zhang said.

Coffee and tea contain caffeine and polyphenols, plant compounds that may protect against brain ageing by improving vascular health and reducing inflammation and oxidative stress, where harmful atoms and molecules called free radicals damage cells and tissues.

Substances in the drinks could also work by improving metabolic health. Caffeine, for example, is linked to lower rates of type 2 diabetes, a known risk factor for dementia.

The researchers analysed records of 131,821 volunteers enrolled in two big US public health studies, the Nurses’ Health Study and the Health Professionals Follow-up Study.

Both took repeated assessments of the participants’ diets, dementia diagnoses, any cognitive decline they experienced and scores on objective cognitive tests for up to 43 years.

Overall, men and women who drank the most caffeinated coffee had an 18 per cent lower risk compared with those who had little or none, with similar results seen for tea.

The effect seemed to plateau at two to three cups of caffeinated coffee or one to two cups of caffeinated tea. No link was found between decaffeinated coffee and dementia.

Further work is needed to confirm whether the two drinks actually protect the brain.

Gold standard trials that randomly assign people to drink caffeinated or decaffeinated drinks for decades before checking for differences in dementia diagnoses are largely impractical.

However, studies could explore whether the drinks drive biological changes linked to brain function, which could be spotted in scans or other tests, Zhang said.

Naveed Sattar, a professor of cardiometabolic medicine at the University of Glasgow, said getting clarity would not be easy, not least because caffeine can have good and bad effects on the brain.

Tea and coffee both contain antioxidants that may be beneficial, and a caffeine boost can motivate people to work, learn and exercise.

In some people, caffeine raises blood pressure, a significant driver of dementia.

“Caffeine does a multitude of things, some which may be beneficial, some which may be harmful, and the net effect can never be estimated until you do a randomised trial,” Sattar said.

Researchers believe about half of dementia cases worldwide can be prevented or delayed by tackling factors such as obesity, smoking, excessive alcohol consumption, hearing loss and high blood pressure.

“Don’t think of coffee or tea as a magic shield,” Zhang said.

“I’d say maintaining a healthy lifestyle, getting regular exercise, having a balanced diet and getting good sleep are all important to get better brain health.”

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Genetic influence on lifespan underestimated by half

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People are twice as likely to inherit their lifespan as previously thought, new research suggests.

The genetic contribution to how long a person lives is around 50 per cent, based on health databases in Denmark and Sweden. This reflects heritability, the share of lifespan differences due to genes.

For decades, many scientists believed genes and ancestry accounted for between about 10 and 25 per cent of longevity.

The research was led by scientists at the Weizmann Institute in Israel, with the Karolinska Institute in Sweden and Leiden University.

The earlier underestimates arose from limited historic health and mortality data, where deaths due to war, infectious disease, risky or unsafe work, accidents, poor diet and lack of medical care were hard to separate in records.

“For many years, human lifespan was thought to be shaped almost entirely by non-genetic factors, which led to considerable scepticism about the role of genetics in ageing and about the feasibility of identifying genetic determinants of longevity,” said Ben Shenhar of the Weizmann Institute.

Environmental forces such as disease or living conditions can mask or confound potential genetic effects.

Hereditary causes of death, for those not killed first by external causes, mean “processes originating within the body, including genetic mutations, age-related diseases and the decline of physiological function with age.” the researchers said.

“If heritability is high, as we have shown, this creates an incentive to search for gene variants that extend lifespan, in order to understand the biology of ageing and, potentially, to address it therapeutically.” said Shenhar.

Other recent research has pointed to a potential role for taurine, an amino acid, in slowing the ageing process.

Scientists have also highlighted the bowhead whale’s 200-year lifespan, attributed to a cellular protein that may protect against carcinogenic mutations.

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Aerska raises US$39m for brain RNA medicines

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Biotechnology company Aerska has raised US$39m in Series A funding to develop brain-delivered RNA medicines.

The company is developing treatments for neurological diseases, including genetically driven forms of Alzheimer’s disease.

This takes Aerska’s total funding to US$60m, months after its seed funding announcement in October 2025.

The company’s platform uses what it calls “brain shuttle” technology to help RNA therapeutics cross the blood-brain barrier, a protective membrane that normally prevents many drugs reaching the brain. RNA interference is a biological process where RNA molecules can silence or reduce the activity of specific genes.

The approach is designed to allow intravenous or subcutaneous administration, with the aim of achieving uniform brain distribution.

The financing was led by EQT Dementia Fund and age1, with participation from Iaso Ventures, alongside existing investors.

Chief executive and co-founder Jack O’Meara said: “The ability to systemically administer RNAi therapies to the brain unlocks a powerful new approach to treating neurodegeneration.

“Partnering with EQT Dementia Fund further strengthens our path to the clinic as we work to translate this capability into meaningful therapies for the treatment of genetically-driven forms of Alzheimer’s disease and other devastating brain disorders.”

As part of the financing, Arno de Wilde, managing director at EQT, Philip Scheltens, partner and head of the Dementia Fund at EQT, and Alex Colville, general partner at age1, will join Aerska’s board of directors.

Scheltens said: “For families facing diseases like Alzheimer’s, Aerska’s approach offers hope for preserving cognitive function and quality of life.

“The team’s strategy of upstream intervention, combined with a focus on the genetic forms of neurological disease, positions them to transform outcomes for populations who have been underserved by current therapeutic approaches.

“We really look forward to working with this talented team to advance this groundbreaking platform.”

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