Alzheimer’s Disease | Biotech Strategy Blog

Can we use immunotherapy to treat or delay Alzheimers Disease?

Preserved section of the Berlin Wall

I have a personal interest in Alzheimers Disease, my mother Audrey died from it three years ago back in 2014.

Since then, I’ve watched with fascination and excitement the progress made in using the body’s own immune system against cancer. There’s still a long way to go, but a revolution in treating cancer is underway, as we’ve been documenting on this blog and the Novel Targets Podcast.

In recent years in the United States we’ve also seen grand initiatives targeting cancer such as Vice President Biden’s Moonshot, as well as large philanthropic support e.g. the creation of the Parker Institute for Cancer Immunotherapy.

Sadly, we’ve not seen the same level of interest in targeting dementia or funding research into new treatments for Alzheimers disease.

In the United States, the media doesn’t talk much about Alzheimers (compared to cancer), unlike for example, in the United Kingdom where any promising data is heralded with headlines that frequently deliver “hype over hope.”

Alzheimers is an insidious disease that removes the ability of the person to advocate and care for themselves, instead placing the burden on families and caregivers, often for extended periods of time. Ultimately many people end up in supported living or nursing homes.

As we debate healthcare insurance in the United States, who is going to pay for the cost of dementia care as the population grows older? Caring for dementia is arguably the greatest public health challenge that the western world faces.

Which is why I was excited to talk with a researcher who is thinking outside of the box and leading the way in how we could use our immune system against Alzheimers.

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Everton FC leads the way in community dementia support

Dementia care is a “quiet crisis” that already touches many families and will touch many more as we live longer in our old age and the huge baby boomer population reaches retirement age.

The Alzheimer’s Research Trust estimate that 1 in 3 over the age of 65 will have dementia by the time they die. Alzheimer’s disease is one type of dementia.

To cope with this explosion, more care will need to be provided in the community.

Mersey Care NHS Trust, who provide mental health care in Liverpool, Sefton and Kirby, have partnered with Everton FC, an English Premier League Club to support members of the local community with dementia.

The innovative program called “Pass on the Memories” (Twitter: @efc_potm) helps more than 120 people with memory loss through activities that take place two days a week at Goodison Park. Support is offered via facilitators in the club and health professionals from Mersey Care.

The meetings help trigger sporting memories, but also engages participants in group social activities and visits, thereby keeping them mentally active and engaged.

When I visited, members of the group were about to head off for a visit to the Museum of Liverpool, which would no doubt stimulate powerful memories for many.

As some readers of the blog may know, my mother Audrey (who died recently at age 89) had Alzheimer’s disease. It’s a progressive disease with no known cure. I watched her memory slowly but surely deteriorate over several years. A keen dancer, she reached a point where she couldn’t remember how to dance anymore.

What Everton FC is doing by lending their support to the Pass on the Memories scheme, is something that sporting clubs around the world should all consider in their communities.

Sporting clubs derive considerable support from local communities and have facilities that are vastly underused outside of games. Many of their fans will sadly develop dementia. Engaging the local community in this way is a tremendous way of giving back.

As social services continue to be cut back in Liverpool due to budget cuts, I’m impressed by the way Mersey Care and Everton FC are helping those with dementia have the best quality of life they can through this type of local partnership.

If it didn’t exist, I expect many people would end up just sitting at home all day with little mental stimulation or interaction.

During my visit to Goodison Park, I spoke with Everton FC Community Engagement Manager, Henry Mooney (@HMooney23) who plays a key role in running the Pass on the Memories program at the club. He told me you don’t have to be an Everton fan to participate. 🙂

Living with Alzheimer’s disease is not easy. Unlike a physical disability, you can’t readily tell if someone has dementia, they look normal much like the rest of us.

Tommy Dunne, 61, was diagnosed with early stage Alzheimer’s disease three years ago. He told me that just because he has dementia, does not mean he is demented. Raising awareness of dementia and getting rid of the stigma associated with it is something we all can help with.

As the number of people with dementia grows, those who provide services (shops, transport etc) will need to be educated on how they can help people with dementia maintain their independence and undertake the activities of daily living that we all take for granted.

I was pleasantly surprised and pleased to see that Tommy is active on Twitter (@TommyTommytee18). It’s a great way to share his experiences.

I’ve included excerpts of the interviews I did with Tommy and Henry Mooney in the radio documentary on dementia that I produced – you can listen via the embedded SoundCloud at the end of this post or using this link.

If you are in the Liverpool area and have a family member with dementia, I encourage you to find out more about this innovative program.

Taking a more strategic view, I’m still shocked by how little progress there has been in drug development to tackle dementia, and in particular Alzheimer’s disease.

In comparison to oncology where research is focused on multiple new targets for drugs, as well as novel biomarkers that can help predict who are more likely to respond, dementia research seems like a record stuck in the groove.

Focusing on one target has failed to yield an effective Alzheimer’s drug despite spending hundreds of millions on clinical research.

More needs to be done to understand the biology of Alzheimer’s disease and generate new insights into potential new targets that at the very least delay the progression of a disease that many of us will possibly end up with in the future.

Update April 30, 2014: Everton FC write up my visit on their Community news site

I was thrilled to hear that John Howard, (@JHowEFC08) Media Officer for Everton in the Community has written about my visit to the Pass on the Memories program. He’s published a really well written post on the Everton FC community website that goes into more detail about the program.

Pieter Droppert interviewing Tommy Dunne. Picture Credit: John Howard, Everton FC

Here’s the link to John’s piece if you are interested in more information: Pieter’s views on Pass on the Memories

Update May 19, 2014: Talking about Dementia on BBC Radio Merseyside Daybreak show

At the start of Dementia Awareness Week in the UK, I was very grateful for the opportunity to go on the May 18, 2014 edition of BBC Radio Merseyside’s Daybreak show, produced by Helen Jones.

I talked about my late mother, Audrey and some of the innovations in dementia care that I’ve written about on the blog. If you have the chance do listen to an excerpt from the show:

Update June 5, 2014: listen to living well with dementia – a personal journey

My research into Everton’s Pass on the Memories program was undertaken while on a BJTC accredited diploma in radio journalism course based at Radio City in Liverpool. You can listen via SoundCloud to the documentary I produced on living well with dementia – a personal journey:

A personal perspective on Alzheimer’s: my mother doesn’t dance anymore

My mother has Alzheimer’s disease – I first suspected some form of dementia when her friends told me that she didn’t dance anymore. Of course she insisted she did, but it was clear she had “forgotten” the steps in a way that was beyond the forgetfulness of getting older.

As a European snow bird she would travel to Malta each year to escape the damp, grey English winters. One year when I visited her in Malta, I noticed when she went up to the hotel dinner buffet, she could not “remember” where to return to.

With a blank and vacant look she would gaze out hoping to find a clue that jarred her memory. Friends gently directed her to the right table and diffused the embarrassment with humor.

Sadly during my visit I saw that she could no longer remember the names of people she had holidayed with for 10 years each winter, or what clothes she had worn the day before. Her holiday companions and the hotel treated her with kindness, but it was the beginning of a decline, and her last winter in Malta.

At home, she has struggled to manage activities of daily living and the need for care has increased. As a family, we’ve endeavored to support her independence for as long as possible, but a nursing home is now in the not too distant horizon.

Which is why I have a personal interest in Alzheimer’s disease. It’s an area where innovation needs to catch up with demand for treatment and therapies, not to treat it when it’s happened – it’s too late to untangle the damage, but to delay it’s occurrence in those at risk.

This week in the New England Journal of Medicine (NEJM), research showed that continued treatment of moderate to severe Alzheimer’s disease with donepezil (Aricept) provides modest cognitive and functional benefits.

By the time moderate to severe disease has set in, the damage has already been done, and the train has left the station metaphorically speaking. Those with this status require the support of caregivers. This study was undertaken in community-dwellings i.e. some form of nursing home or care facility.

In their NEJM paper, Robert Howard of the Institute of Psychiatry & UK colleagues assessed changes in Standardized Mini-Mental State Examination (SMMSE) & Bristol Activity of Daily Living (BADLS) scores in moderate to severe Alzheimer’s patients who received donepezil or memantine in a double-blind, placebo controlled trial.

Patients continued to decline over the course of the study, so what the study showed was that by giving a cholinesterase inhibitor, the rate of decline was slowed. The functional benefit was equivalent to 32% of the total deterioration seen over 12 months.

However, dramatic as this significant benefit sounds, the author’s rightly caution that the improvements in cognition and function were small relative to the overall decline in cognitive and functional status seen in all patients.

While this paper offers evidence-based medicine for the continuation of donepezil in those with moderate to severe disease, this treatment does not lead to a cure or restoration of function.

A study sample size of 430 was estimated to give a 95% power to detect a 1.0 point difference in SMMSE scores between donepezil and placebo groups, and 90% power to detect a 2.0 point difference. In the end a total of 295 participants were enrolled.

The results showed that:

“Patients who were assigned to continue taking donepezil, as compared with those assigned to discontinue donepezil, had scores on the SMMSE that were higher (indicating better cognitive function) by an average of 1.9 points (95% CI, 1.3 to 2.5; P<0.001) and scores on the BADLS that were lower (indicating less functional impairment) by an average of 3.0 points (95% CI, 1.8 to 4.3; P<0.001).”

The researchers noted that:

“The severity of dementia at entry significantly influenced the effect of donepezil on SMMSE scores, with larger benefits observed in patients with moderate disease (SMMSE score, 10 to 13) than in those with severe disease (SMMSE score, 5 to 9).”

More information on the study design and detailed results can be found in the published NEJM paper.

My Mother takes donepezil and I’m pleased to see that there’s now some clinical data to support its continued use, as she will no doubt progress.

All those with loved ones who have Alzheimer’s will be pleased with any news that delays the progression of this debilitating disease.

Reference

Howard, R., McShane, R., Lindesay, J., Ritchie, C., Baldwin, A., Barber, R., Burns, A., Dening, T., Findlay, D., Holmes, C., Hughes, A., Jacoby, R., Jones, R., Jones, R., McKeith, I., Macharouthu, A., O’Brien, J., Passmore, P., Sheehan, B., Juszczak, E., Katona, C., Hills, R., Knapp, M., Ballard, C., Brown, R., Banerjee, S., Onions, C., Griffin, M., Adams, J., Gray, R., Johnson, T., Bentham, P., & Phillips, P. (2012). Donepezil and Memantine for Moderate-to-Severe Alzheimer’s Disease New England Journal of Medicine, 366 (10), 893-903 DOI: 10.1056/NEJMoa1106668

ARVO 2011 Using the eye as a window into the brain

By Pieter Droppert on May 4, 2011

Due to the pressure of other commitments, I only had the pleasure of attending the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) for two days, but one of my key take home messages from the meeting is how we can use the eye as a window into the brain. This is particularly relevant to Alzheimer’s research.

ARVO researchers at a lunchtime workshop that I attended asked the question of what can we learn from shared disease mechanisms in age-related macular degeneration (AMD), Alzheimer’s Disease (AD) and Glaucoma to devise therapies of the future?

What I learnt in the introduction by Nicholas Bazan from LSU Health Sciences is that both AD and AMD are both multifactorial, genetically complex, progressive, late-onset neurodegenerative conditions. Common features include:

Age-related neurodegeneration
Amyloid precursor protein mis-processing
Non-resolving inflammatory response
Selective apoptotic cell death

Researchers in the workshop presented early experimental findings.

Catherine Bowes Rickman from Duke presented data that showed anti-amyloid immunotherapy blocks retinal pigment epithelium (RPE) damage and visual function defects in an AMD-like mouse model. Interesting questions were raised as to whether mouse Aß aggregates differently to human, so is this a good model?

Adriana Di Polo from the University of Montreal discussed Glaucoma and AD: common neurodegenerative pathways and therapeutic targets. It was interesting to note that high rates of visual abnormalities, including glaucoma, have been reported in AD patients, but causality has not been established. Neuronal loss in both glaucoma and alzheimer’s disease occurs via common cell death processes including altered metabolism of Amyloid Precursor Protein (APP) and Aß.

What Di Polo highlighted in her talk was the potential to use therapies effective in one disease to treat the other e.g. galantamine is approved for treatment of mild to moderate AD symptoms. Because it crosses the retinal-brain barrier and has high bioavailability, she presented results using this in an animal model of glaucoma.

Her conclusion was that “therapeutic modalities that promote neuroprotection in AD may be useful in glaucoma and vice versa.”

The third speaker of this fascinating workshop was Ian Trounce from Melbourne, who challenged the Amyloid theory of AD. His hypothesis was that sAPPα may trigger oxidative stress in mitochondria and be the problem. He discussed the increasing acceptance/overlap in pathologies between Parkinson’s and AD. He presented data that sAPPα overexpression protects retinal ganglion cells (RGC) from rotenone via PI3K-AKT activation.

Critical feedback on the three presentations was provided by Guy Eakin of the American Health Assistance Foundation (AHAF) and Imre Lengyel from UCL.

As Dr Lengyel succinctly notes in his UCL Institute of Ophthalmology bio:

“It appears that the development of age related macular degeneration (AMD) and Alzheimer’s disease (AD) share similar histopathology, vascular risk factors and genetic predisposition. In addition, the development of AMD appears to use similar or identical steps on the cellular and molecular levels to AD: vascular damage, oxidative stress, inflammation, extracellular protein and peptide degradation or deposition, and the role for lipids and trace elements (especially zinc) in the degenerative process are amongst the many common features. Furthermore, amyloid beta peptides are an integral part of drusen (the hallmark lesion in AMD) and their formation might be similar to plaque formation in AD.”

I applaud ARVO for looking at how the eye can be used as a window into the brain. It raises the intriguing prospect that research on AMD may not only help understand the cause of AD, but that the eye may serve as an experimental model for future new treatments. Collaboration between Opthalmology and Alzheimer’s researchers is something I expect and hope we will see more of.

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Posts tagged ‘Alzheimer’s Disease’