香港六合彩中特网

It is estimated that there are currently 944,000 people living with dementia in the UK and 52% of the UK public 鈥� 34.5 million 鈥� know someone who has been diagnosed with a form of the disease. Over 60% of people living with the condition are thought to have Alzheimer鈥檚 disease.

Dementia is the nation鈥檚 biggest killer and has been the leading cause of death in women since 2011. However, there is currently no cure.

香港六合彩中特网 is determined to tackle this growing crisis with one of the world鈥檚 largest neuroscience communities, access to a patient population of more than six million and the construction of a new neuroscience facility at 256 Grays Inn Road, enabled by a visionary community of partners and philanthropic funders.

And, over the past year, the work of the university鈥檚 talented researchers and clinicians has helped see the success of trials involving drugs such as Lecanemab and ALN-APP - showing that it is possible to slow the rate of cognitive decline in people with Alzheimer鈥檚 disease and giving hope to millions across the globe.

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Where it started

The results of the Lecanemab trial were published in November last year. It was found to slow down progression and reduce memory decline by targeting beta amyloid 鈥� a plaque that builds up in the brains of people with Alzheimer鈥檚 disease.

Professor Sir John Hardy (香港六合彩中特网 Queen Square Institute of Neurology) was the first to identify the role of amyloid in Alzheimer鈥檚 disease 30 years ago, after he began working with Carol Jennings and her family.

Carol reached out to Professor Hardy and Professor Martin Rossor (香港六合彩中特网 Queen Square Institute of Neurology) in the mid-1980s, after her father, his sister and brother, all developed symptoms and were diagnosed with Alzheimer鈥檚 in their 50s.

Intrigued, Professor Hardy embarked on research to determine whether there were any genetic differences between those who had Alzheimer鈥檚 and those who didn鈥檛.

And, five years later, his team discovered a mutation to the amyloid precursor protein (APP) gene, which creates the amyloid plaques that form in the brain during Alzheimer鈥檚 disease 鈥� causing them to become overactive and signalling for ongoing inflammation, which can disrupt normal processes in the brain.

As a result of the findings, in 1992, Professor Hardy and his colleague, Professor David Allsop, published the amyloid cascade hypothesis, which helped explain:

• The brain appearing smaller due to the death of brain cells
• The build-up of amyloid protein
• Tangles with tau (a toxic protein that causes neuronal death)

It was this theory that helped pave the way for the development of Lacanemab, which provided a 鈥渕odest鈥� yet 鈥渉istoric鈥� breakthrough for Alzheimer鈥檚 treatment.

The drug 鈥� developed by companies Eisai and Biogen - was shown to slow the rate of cognitive decline in people with Alzheimer鈥檚 disease.

Professor Hardy said: 鈥淭his trial is an important first step, and I truly believe it represents the beginning of the end. The amyloid theory has been around for 30 years so this has been a long time coming. 鈥淚t鈥檚 fantastic to receive this confirmation that we鈥檝e been on the right track all along, as these results convincingly demonstrate, for the first time, the link between removing amyloid and slowing the progress of Alzheimer鈥檚 disease.鈥�

And, in July, the drug was fully approved by the US Food and Drug Administration (FDA) as a treatment for early Alzheimer鈥檚 disease.

However, Lecanemab wasn鈥檛 the only drug to grab headlines in 2023.

A second turning point

In July, a new drug, Donanemab, was found to slow cognitive decline in Alzheimer鈥檚 disease by around a third, in a global trial involving 1,736 people aged 60 to 85 with early-stage Alzheimer鈥檚.

The drug, made by Eli Lilly, works in the same way as Lecanemab, and helps in the early stages of the disease by clearing amyloid buildup in the brains of people with Alzheimer鈥檚 disease.

One American woman on the drug trial claimed that her condition improved so much that she was even able to drive and read again.

Professor Hardy and Dr Cath Mummery (both 香港六合彩中特网 Queen Square Institute of Neurology) were at the Alzheimer鈥檚 Association International Conference (AAIC) when researchers announced the findings to a room of cheering scientists and clinicians from around the world.

No magic bullets

While they admit that the results were 鈥済reat news鈥�, both Professor Hardy and Dr Mummery wanted to make clear that there were some 鈥渋mportant caveats鈥�. For example, it is unclear of the effect of the drug after 18 months and claims about the drug reducing disease progression by 60% were misleading.

Writing in the Daily Mail, they said: 鈥淥n average, the rate of mental decline slowed by around 35% - reduced to 22% once patients with more advanced disease were taken into account.鈥�

Additionally, both Donanemab and Lecanemab come with risks. For example, brain swelling was a common side-effect in up to a third of patients in the Donanemab trial. And while this was resolved in most cases, three volunteers died as a result.

Dr Mummery and Professor Hardy, said: 鈥淭hese powerful drugs carry significant risks.鈥�

They added: 鈥淚f it were given in the UK, patients would need to be carefully monitored.鈥�

Another drug, Aducanumab, was also rejected earlier this year by European regulators over safety concerns and a lack of evidence that it was effective enough for patients.

鈥楨xciting鈥� new techniques

Whilst both Lecanemab and Donanemab focus on getting rid of amyloid proteins and need to be administered around every two to four weeks, Dr Cath Mummery is leading the UK arm of a global trial focused on preventing the amyloid protein from being produced in the first place 鈥� with effects that could last up to a year.

The ALN-APP trial started in early 2023, it is currently recruiting and so far involves 20 people, including eight in the UK.

Interim results of a phase one trial published at a medical conference in July, suggest that a single dose of the treatment reduces levels of amyloid precursor protein (APP) by up to 80%. APP is the precursor to amyloid that can build up in the brain.

The results were also found to be long lasting with tests showing that levels were still on average 65% lower six months later.

It is hoped that, if given early enough, the treatment could stop patients developing symptoms of Alzheimer鈥檚 by 鈥榮ilencing鈥� the gene that helps cause the disease.

Dr Mummery said: 鈥淲e got the first patients in the UK into the trial. The trial involves giving the interference RNA drug to reduce the amount of protein being produced. The drug uses the cell鈥檚 own machinery to hijack the normal cell process that regulates translation of a gene into a protein. And what鈥檚 really cool is that it catalyses the normal mechanism, and so the effect of one dose can last a really long time.鈥�

Interference RNA treatments have been approved for use since 2019 for several other diseases, including amyloidosis (where a toxic protein attacks organs in the body), acute hepatic porphyria (a genetic condition affection the nervous system) and primary hyperoxaluria type 1 (a condition that causes severe kidney stones). However, this is the first time that it has been tried in the brain for any disease.

The treatment is given via an injection in the lower back, directly into the cerebrospinal fluid surrounding the spinal cord 鈥� enabling it to reach the brain easily. The initial results show that the drug is safe.

The impact

One of the eight UK participants to be involved in the trial is Anne Warburton, 68.

Anne began repeating herself shortly before her 60^th聽birthday and has now been diagnosed with 鈥渕ild to moderate鈥� Alzheimer鈥檚.

Although she is still able to enjoy hobbies such as gardening, socialising and spending time with family and friends, her symptoms are gradually getting worse.

Speaking in the Sunday Times, her husband Peter, 69, said: 鈥淚t means forgetting appointments, forgetting things she promised to do, misplacing items on a daily basis.鈥�

The couple don鈥檛 know whether Anne was one of the 14 participants to receive the active drug. However, in the next multiple-dose stage of the trial, all participants will receive the genuine treatment.

Peter said: 鈥淲hen we decided to participate it was made very clear we were giving a gift to the medical and scientific community. 鈥淭here should be no expectation that we would receive anything personally from this. But obviously we are only human, we hope this drug will give Anne a better cognitive outcome.鈥�

The future

Now the team are starting the second part of the stage 1 trial before embarking on a larger phase 2 trial, where they hope to recruit enough people to show a slowing in cognitive decline alongside evidence of reduced production of amyloid and slowed disease.

Although there is a long way to go before the treatment is available on the NHS, Dr Mummery believes that, in the future, this kind of treatment could be effective in 鈥渉elping to prevent disease rather than slow it down鈥� 鈥� something she describes as being 鈥渞eally exciting鈥�.

The method could also extend beyond Alzheimer鈥檚 to treating other genetic and non-genetic diseases involving amyloid in the future, including Cerebral amyloid angiopathy (CAA) which can cause brain swelling and bleeds, and even Down syndrome.

Dr Mummery says: 鈥淚鈥檝e been involved in genetic therapies for eight years now. For me, conducting trials is a privilege: firstly, any trial gives the opportunity to give someone with this disease some control back of their life; being part of the team doing the trial is super-exciting regardless of at the precise trial 鈥� and that鈥檚 really why I鈥檓 in the business of conducting trials.

鈥淩egarding this trial in particular, I think we are starting to get much more intelligent at looking at how to target diseases. We are starting to use precision medicine rather than a blunderbuss, we are trying to precisely change what is happening and, to me, that makes an awful lot of sense in medicine.

鈥淏eing at the cutting edge of something that has never been done before is brilliant. I wouldn鈥檛 do any other job, I love it and feel honoured to be able to work in this area.鈥�

Links

• 香港六合彩中特网 Queen Square Institute of Neurology
• 香港六合彩中特网 Brain Sciences
• 香港六合彩中特网 Giving: Neuroscience

Images

• Doctor diagnose and checking brain testing result with computer and AI, robotic on virtual interface in laboratory, innovative technology in science and medicine.聽Credit:聽聽on iStock
• Amyloid plaques are misfolded protein聽aggregates between neurons - Alzheimer's disease illustration.聽Credit:聽聽on iStock
• Professor Sir John Hardy
• Dr Cath Mummery
• Closeup of an old caucasian man and an old caucasian woman sitting in a couch holding hands with affection. Credit:聽聽on iStock