One young scientist’s quest to find a cure
Victoria Lambert meets the young scientist inspired by his own grandfather to start a research mission to cure the brain disease
Joseph Jebelli recalls the childhood visits of his grandfather, Abbas, with huge affection. “He’d often visit us in Bristol from Tehran where he lived,” says Jebelli, a softly spoken 31-yearold scientist. “I remember him as this enchanting and mysterious figure, yet very energetic, and extroverted. He adored my sister and I, telling us about the great Persian kings.”
The “leathery” old man would arrive carrying suitcases stuffed with pistachio nuts and Persian sweets, “smiling until the corners of his eyes wrinkled as he handed us our gifts”.
But by the time Jebelli was 12, Abbas was not himself any more. “He became more introverted, indefinably peculiar. He was only 68, but quite confused.”
Four years later, his grandfather no longer recognised Jebelli. “He spent a lot of time disengaged from the world with a glassy, vacuous stare.
“He would wander off from the dinner table and my dad would have to find him. My grandfather didn’t know where he was or what he was doing.”
Loss of navigation is one of the first signs of Alzheimer’s disease – although at the time, the family put Abbas’s confusion down to old age.
The trips to Bristol stopped, and Joseph’s father, Abol, would visit Tehran instead. There, he learnt Abbas was deteriorating further. “He would get lost and head back to the old family home, which he had left decades before,” says Jebelli.
“Things came to a head when he could no longer recognise his wife, Afsana, and started calling her by the name of his first wife.”
In 2003, when Jebelli was
17, Abbas was diagnosed with Alzheimer’s disease. Yet while his grandfather suffered, Jebelli’s maternal grandmother “was as sharp as a pin”.
This sparked curiosity in the mind of the teenager: why did some elderly people decline and others not?
It prompted him to go on something of a quest to understand what had happened to his grandfather’s brain. He wanted to “understand how we first lock horns with the disease” that claimed his grandfather.
He studied neurobiology, first at University College London and then the University of Washington, Seattle, specialising in Alzheimer’s research.
What he learnt both in the lab and talking to patients, doctors and families has resulted in a book, In Pursuit of Memory, which recounts the history of the disease and the strides being taken to understand – and ultimately cure – the illness.
Best of all, the book is positive. Jebelli says: “This is a really exciting time for Alzheimer’s. We are finally targeting the underlying causes, not just treating symptoms.”
Hope cannot come soon enough. Alzheimer’s is now acknowledged as the leading cause of death in the UK, responsible for more than 61,000 fatalities, according to the Office for National Statistics – a staggering 11.6 per cent of deaths. Sufferers can succumb to infections, especially pneumonia (Alzheimer’s weakens the immune system), as well as complications such as stroke or heart failure.
Why is it now so prevalent? “The biggest factor is that we are living longer,” says Jebelli. “There is better diagnosis, too. Although we think only 48 per cent of people with dementia are spotted even now; 52 per cent just live with it.”
The question of diagnosis is one of the great mysteries of Alzheimer’s – it cannot be absolutely confirmed until brain tissue is examined post-mortem. But that is changing, says Jebelli. “We do tests of memory, cognition, spatial awareness, and we can scan the living brain for signs of beta-amyloid.”
A naturally occurring protein, beta-amyloid accumulates in clumps, known as plaques, inside the brain of someone with Alzheimer’s, destroying healthy neurons, and is thought by some scientists to be its cause.
But there are two other major theories – one involving the protein tau (tubulin-associated unit), which can become contaminated and slow down the messages travelling between our brain cells. The third is a genetic mutation, ApoE4, which can interfere with the body’s ability to absorb glucose, leading to the brain being starved of energy.
None of these theories has been conclusively proven, says Jebelli. But each offers new potential for drug targets and therapies. This is crucial when the only options so far have been the Aricept generation of drugs, which only offer relief of symptoms for six months to a year.
Obviously, though, any new therapies are no use without a better diagnostic tool. Scientists can find markers in spinal fluid via a lumbar puncture to predict with accuracy who will get Alzheimer’s in 20 years’ time, but the test is invasive and painful, and currently used only in medical research. Scientists in Georgetown, Washington, are exploring ways diagnosis could be made via eye examination.
But the best hope, says Jebelli, is research looking into biomarkers that can accurately predict the likelihood of Alzheimer’s, which could be identified by a blood test – avoiding the confusing, drawn-out process that Jebelli’s grandfather experienced.
“Alzheimer’s starts long before the symptoms start to show. So the goal is very early diagnosis in middle age, treated with a drug, which would stop the disease in its tracks before it had begun to cause brain damage. Even if we couldn’t stop people getting Alzheimer’s, we could enable them to outlive the onset of symptoms.”
By 2025, Jebelli adds, results should be available from trials of drugs that could do just that by targeting betaamyloid, clearing the plaques or preventing them building up.
What about those patients whose brains are already stifled – is there any hope?
“There is amazing work being done with stem cells, growing them in petri dishes, turning them into brain cells, but it is a long way off.”
Could the future include transplanted brain tissue? “Never say never,” Jebelli replies.
Given his family history, would he be interested in knowing whether he carried a gene for the disease? “There is still no treatment available, so what would be the point?”
There is good evidence, however, that lifestyle interventions can help ward off the illness. Jebelli and his colleagues follow that advice, by eating a Mediterranean diet, getting plenty of sleep and exercise, and keeping stress to a minimum.
“I guess I do fear developing Alzheimer’s,” he says, “yet I am optimistic. I think we are genuinely close to developing a drug to prevent or alleviate the pain and suffering that goes along with it.”
His grandfather died of pneumonia in 2012, at the age of 82, loved and cared for by his three daughters.
Jebelli knows that Abbas – to whom is the book is touchingly dedicated – would be very proud of his work. “He was very unwell by the time I started researching it. But I like to think he knew what I was doing and why.
“The disease destroys the part of your brain that contains your short-term memory first,” adds his grandson. “But one of the last parts it reaches is that which controls emotion.
“Alzheimer’s can’t take that love away.”
Tomorrow In Monday’s Telegraph, Joseph Jebelli explains how we can guard against Alzheimer’s