Dementia

Baroness Greenfield Excerpts

Thursday 18th January 2024 Grand Committee

[Baroness Greenfield (CB)]

I thank the noble Baroness, Lady Browning, for drawing attention to this timely and important issue. I am a neuroscientist working on brain mechanisms that underlie dementia and, accordingly, I declare an interest as the founder and CEO of a biotech company, Neuro-Bio Ltd, which is developing a novel approach to the diagnosis and treatment of Alzheimer’s disease. From first-hand experience, I can speak to the importance of strengthening the dementia research landscape. It is only by increasing resources for research that we will ever be able to realise if not a cure then, very plausibly and at last, a truly effective treatment. I thank the Alzheimer’s Society for its assistance in preparing these remarks on the situation in the UK, where, as we heard from the noble Baroness, Lady Browning, some 900,000 people are already living with dementia, a figure expected to rise to 1.6 million by 2040. As we also heard, one in three of those born today will develop the condition in their lifetime.

Yet combating this devastating disease is still not seen as the political priority it needs to be, and it has been historically underfunded. For example, just 31p is spent on dementia research for every pound invested in cancer research. That said, we should welcome the launch last year of the Government’s £95 million commitment to the Dame Barbara Windsor dementia mission, but we now need to see a delivery timeline for this funding, and we urgently request further detail about how the Government plan to invest the money.

But it is not just about the money. The APPG on Dementia, of which I am a proud member, released in 2021 a report entitled Fuelling the Moonshot, which found that people affected by dementia feel a sense of empowerment from being involved in research, but also that patients are often unaware of the opportunities to take part. This has to change—action must be taken to improve participation in, and access to, clinical trials. Recent investment in research is welcome, but it will be wasted without increased participation in these studies.

Moreover, any consideration of those living with dementia also needs to include the carers. This is where social issues should be given equal attention. In 2011, I gave a lecture tour on behalf of Alzheimer’s Australia, and I still vividly recall a conversation with a husband who had been caring for his wife, to whom he had been married for many decades. In the early hours of one morning, when he was changing her incontinence pads during a bout of diarrhoea, she, the love of his life, just stared at him, questioning who he was. It was then, he said, that he snapped. This gentleman described his situation as a “living death”, which is a phrase that I have heard repeated by other carers of those with dementia. Often, those closest undergo all the experiences of bereavement, no longer able to share memories with a very special individual who none the less is still breathing. The big difference is that society does not accord them the time and support it would to those grieving an actual death.

We need more resources for research, action on optimising clinical trials and wraparound support for the carers. Indeed, as highlighted in this debate, we need parity in health and social care. Dementia presents the biggest unmet clinical need of our time. Let us work towards a future where we are no longer haunted by the spectre that perhaps, one day, we will ask our spouse who they are, or that they in turn will describe their life with us as a living death.

Ageing: Science, Technology and Healthy Living (Science and Technology Committee Report)

Baroness Greenfield Excerpts

Wednesday 20th October 2021 Grand Committee

[Baroness Greenfield (CB)]

I thank the noble Lord, Lord Patel, for the opportunity to consider how we might enhance the prospect of a long and healthy life. Accordingly, I declare an interest as founder and CEO of Neuro-Bio Ltd, a biotech company developing an innovative treatment for dementia, specifically Alzheimer’s disease. As the noble Lord correctly predicted, I will focus most of my comments on that subject.

Alzheimer’s is a neurological condition characterised by memory loss, disorientation and general cognitive impairment. It is a disease typically, though not exclusively, of older people. One in six over the age of 80 have dementia, a condition that affects as many as 70% of residents in care homes. The spectre of Alzheimer’s is one of the cruellest potential scenarios awaiting us in later life. While heart disease and cancer are serious, often disabling and sometimes terminal, you can still reminisce over old photographs and spend meaningful and precious time with your grandchildren. These life-enhancing moments are gradually closed off to an individual with dementia.

Despite hearing from witnesses from both Alzheimer’s Research UK and the Alzheimer’s Society, there seems to be no substantive discussion in the report of the very real threats that Alzheimer’s currently poses to enjoying a healthy older age. It is cited as the most common cause of death for women, then flagged in relation to air pollution and reported as mitigated by cognitive reserve. That is three mentions of one of the most important issues related to ageing and its potential alleviation by science.

The Alzheimer’s Society’s website reports facts and figures that are truly concerning. First, there is the societal impact of dementia as one of the main causes of disability later in life. There are currently around 850,000 sufferers in the UK; this figure is projected to rise to 1.6 million by 2040. This year, 209,600 people are expected to be diagnosed with dementia; that is one person every three minutes.

Secondly, there is the economic factor. The total cost of care for people with dementia in the UK is £34.7 billion. This is set to rise sharply over the next two decades to £94.1 billion by 2040.

Thirdly, there is the impact on carers, in addition to the financial and mental health repercussions of perhaps giving up a job to care for a loved one. On more than one occasion, I have heard this daily existence described as a living death.

Since these problems are not raised in the report, it is unsurprising that there are no recommendations specifically to resolve them. I want to make a few suggestions for brief consideration here. The only successful way to combat Alzheimer’s disease will be to devise an effective treatment. In turn, this is dependent on gaining insight into the underlying brain processes. Further research, both basic and translational, is thus essential.

However, dementia research is desperately underfunded. For every individual living with the condition, the annual cost to the UK economy is more than £30,000, yet only £90 per patient is spent on research. Five times fewer researchers choose to work on dementia than on cancer. Yet if we could come up with a means of delaying the onset by five years, the number of deaths from the condition would be halved, saving 30,000 lives a year.

Admittedly, various recommendations in the report are concerned with drug development in a more general sense in relation to older people. However, sadly and strangely, no specific issue is raised in relation to improved therapies for Alzheimer’s disease. An obvious and predictable recommendation would be to make more funds available for research, be they from public, private or philanthropic sectors.

Just as important, but much less obvious, is the question of how such resources should then be deployed. Currently, the majority of funding is directed at just one strategy to combat the histological marker in the brain—amyloid—as it is a frequent feature of Alzheimer brains. However, drugs designed to antagonise amyloid at best only slow down the progression of the disease. There is increasing doubt that it is the primary cause of the neurodegenerative process. The report could have highlighted the lack of success of current treatments and thus argued the case for promoting initiatives pursuing innovative lines of inquiry. In this way, we could truly understand the degenerative mechanism in order to intervene with a successful pharmaceutical strategy.

The hunt for an anti-Alzheimer’s drug that actually works is far from straightforward. As yet, there is a no accepted narrative for how and why neuronal loss starts, nor for—of equal importance—how it is perpetuated for decades before the classic profile of cognitive impairment presents. Unless and until we understand what is happening in the brain for this period, we will only ever be able to deal with downstream symptoms, such as amyloid accumulation, rather than halting cell loss by intercepting the driver of the disease.

The second reason for failure to date is the lengthy time window of 10 to 20 years between the onset of cell loss and the eventual presentation of cognitive impairment. Any treatment initiated at this late stage is comparable to closing the stable door after the horse has bolted, as the pernicious cycle of cell loss would have been under way for decades. Analogous to the measurement of cholesterol for detecting cardiovascular problems, we need a routine blood test, say, that would enable easy screening to determine whether the degenerative process was already in train, even though the person may feel perfectly fine at the moment. Imagine if we had a blood biomarker indicating early on that degeneration had already started, well before the behavioural symptoms of Alzheimer’s were apparent. Imagine if we had a drug that stabilised cell loss and halted neurodegeneration. If such a drug were taken before the symptoms became apparent, those symptoms may never arise—not a cure in the literal sense, but effectively just that.

What is stopping us developing such a biomarker and such a drug? We need to facilitate more innovative lines of research and challenge existing dogma. Admittedly, there will be false dawns and blind alleys. There will be risks to take and cynicism to overcome, but that is the only way we will ever develop an effective treatment for Alzheimer’s disease. The American physicist and philosopher Thomas Kuhn famously argued that science does not evolve gradually towards truth but has a paradigm; that is, it has an accepted approach that remains constant until anomalies start to accumulate, and accumulate to such an extent that it is finally accepted that established thinking cannot explain the phenomenon in question. A completely new theory must then be conceived—a paradigm shift. If we are to understand and tackle this devastating condition successfully, we are long overdue for such a shift in our thinking.

Alzheimer’s disease is not an inevitable consequence of ageing, but it is a disease of old age. In my view, the report has missed a golden opportunity to draw attention to its current impact and future threat. Most importantly, it has missed the opportunity to promote new strategies to consign dementia to being a disease of the past. Only when this happens will we be able to have justified confidence in an old age that is not only able-bodied but clear-minded.

Regenerative Medicine: S&T Committee Report

Baroness Greenfield Excerpts

Thursday 13th March 2014 Lords Chamber

[Baroness Greenfield (CB)]

I add my voice to those of the other noble Lords in congratulating the noble Lord, Lord Patel, on bringing attention to this timely and important report. He and others have already spoken eloquently on the wider issues surrounding stem cell research, so I shall restrict my comments to my own particular area: diseases of the central nervous system.

While other conditions such as heart disease and cancer are devastating, we all fear in particular the disorders that destroy our brains. The report discusses the wonderful prospect that in the next five years treatments are likely to be available for stroke and multiple sclerosis. However, only under a section on longer-term possibilities is Parkinson’s disease mentioned.

The neurodegenerative diseases of Alzheimer’s and Parkinson’s target the very essence of what it means to be human: what it means to move freely, to smile, to think, to speak and to have memories—indeed, to be a unique individual. The problem is that, as yet, we do not know why key brain areas in each case embark on the initial cycle of self-destruction or why it occurs only in certain brain regions and not in others. Because we do not currently understand the basic mechanisms, we cannot get to the root of the problem. The best that we can do is to combat the symptoms.

As brain cells die, they release less and less of their essential chemical messengers. Current strategies, therefore, are to offset the dwindling level of those naturally occurring chemicals with drugs, but here the problems are several-fold. First, as with all drugs, the treatment will permeate into areas of the brain and body where it is not needed and hence cause side-effects. For example, with Parkinson’s disease, treatment with the drug in current use, L-dopa, will supply the necessary chemical messenger, dopamine, to the area of devastation, but will also raise levels of the same chemical elsewhere in the brain, and this can often result in psychotic side-effects, with disturbing hallucinations. Even when such treatment offers temporary alleviation of the patient’s basic condition—or slowing down of the deterioration, as in the case of the anti-Alzheimer’s drug Aricept—it has proved hard to convince organisations such as NICE that the costs are worthwhile.

The situation is made even worse when we consider how many more of us are going to need such treatment in the future. Today, nearly a million people suffer from Alzheimer’s or Parkinson’s or both, and that number is expected to double by 2050. The total cost of caring for one person with dementia can be up to £30,000 per patient per year—plus the additional costs caused by loss of earnings.

Even more sobering, beyond the mere economics, is the human cost. For every person suffering from either Parkinson’s or Alzheimer’s, let us say there are 10 people who care about that individual. Hence, as the number in the UK reaches almost 2 million by the middle of this century, almost 20 million lives could be affected by those devastating disorders.

So there is a huge and growing need: a need that is currently unmet. Stem cell therapy offers an exciting and realistic alternative. The rationale is completely different from that of conventional treatments. The idea is not to treat the symptoms, but to harness regenerative biological mechanisms so that new cells are created. That would be a real cure. It would not be merely replacing the chemicals that are lost as a result of cell death, but actually replacing the neurons themselves.

Some cases of Parkinson’s disease have been successfully treated using human foetal cells; however, such tissue is hard to obtain, and the ideal would be switch to human embryonic stem cells. Those cells are derived from very early embryos, at the stage when the embryo is a microscopic ball just a few days old and consisting of only one to 200 cells. Not only are they immortal, they can produce every type of cell in the body. By introducing such cells into the appropriate environment within the brain, they will actually become the brain cells that have been lost.

There are, inevitably, potential downsides, As a neuroscientist, I am unable to comment with any authority on the ethical or financial issues, so I will restrict my caveats to technical issues. The first would be immune rejection of the new cells. However, that can be overcome by immunotolerising patients or even by immunosuppression. Such therapies have side-effects, but the risk-benefit ratio compared to that with conventional drugs is greatly shifted in favour of the positive.

A further problem is that stem cells could proliferate out of control in the brain and therefore become a tumour. However, to date, there is no clinical evidence that that has occurred with stem cell therapy and, in any event, it could be circumvented by biochemical chicanery—for example, manipulating stem cells so that they divide at a few degrees hotter than would normally be the case in the living brain.

Another issue is that implanted stem cells may produce excessive amounts of chemical messenger compared to normal levels. In principle, however, once stem cells have repopulated the brain, they should behave like their naturally occurring predecessors and release chemicals within the normal range as and when they are stimulated and interacting in their normal brain environment. In any event, conventional drugs already produce excessive amounts of chemical messenger, but that can be controlled by current treatments.

Finally, we must be careful not to conflate Parkinson’s and Alzheimer’s diseases. They are very different conditions and are differentially tractable to stem cell therapy. Parkinson’s disease is much more localised in the brain than Alzheimer’s, and therefore it will be much easier to locate where the stem cells should be placed. However, there is often a co-pathology—patients presenting with both Alzheimer’s and Parkinson’s diseases—so in these cases perhaps the alleviation of the movement symptoms of Parkinson’s may help in the patient’s quality of life, not least because we know that the better that people can move physically, the more that they can sustain a good blood supply to the brain.

There is now a growing body of evidence that physical exercise can enhance the natural growth of brain cells, a phenomenon known as neurogenesis, as well as the proliferation of blood vessels, therefore bringing more oxygen to the brain, which improves its functioning. There are even some claims that Alzheimer’s disease could be less prevalent in those who exercise routinely. So a treatment for patients suffering from both Alzheimer’s and Parkinson’s that enabled them to move more freely might in the long term be more generally beneficial.

Some might say that introducing the cells into the brain would be problematic, but the brain surgery required is modest. Modern stereotactic surgery is performed under local anaesthetic, with only a small hole made in the skull and a fine needle introduced—a bit like drilling for oil using precise three-dimensional co-ordinates. The area targeted can then be localised.

In summary, we have reason to be confident that, although not without risks or difficulties, stem cell therapy could be a chance to harness the nervous system’s natural mechanisms to regenerate itself. In the case of neurodegenerative disorders, though, much more research needs to be done.

I commend the authors of the report for increasing the chances that we will,

“facilitate the translation of scientific knowledge into clinical practice and encourage its commercial exploitation.”.

Still, far more money needs to be devoted to research into the use of stem cells in brain disease, which at present is a poor relation to heart disease and cancer. If these recommendations are implemented, the horizons could be very bright, not just for those with Alzheimer’s and Parkinson’s, who are currently condemned to a highly disabled life and an even bleaker future, but for everyone who cares about them.