Tuesday, August 9, 2022

Dementia At 7 Years Old

August 12, 2008 by  
Filed under NPC Family Stories

Ben Scott developed dementia at SEVEN

One family reveals their truly heartbreaking story

04th August 2008

Like any proud dad, Andrew Scott loves to take pictures of his son, seven-year-old Ben. There’s Ben running around a field playing catch with his three sisters; Ben screaming with delight on the water ride at an adventure park; Ben sitting on the back step, splashing a bucket of water.

But over the past three months Andrew’s photography has become something of an obsession. He has taken literally hundreds of pictures of Ben, trying to capture every day of his son’s life, part of a project he calls the Book Of Ben.

‘We went away on holiday recently and I took 400 shots, almost all of Ben. Click, click, click – I couldn’t stop,’ says Andrew. ‘It’s his smile I’m trying to get. I want it on film so we never forget . . .’

Ben Scott

Fading: Ben Scott, here at the age of about 2, will lose his ability to smile or even recognise his parents

Two months ago Andrew and his wife Lyndsay, who live in Yeovil, Somerset, were told their son has a form of dementia.

At just seven, Ben is facing the kind of harrowing decline we associate with old age. But he’ll be lucky to live to 20.

Already, his speech is slurred, and within a few years he will be unable to walk, speak or recognise those closest to him, trapped in his immobile body, unaware of anything around him.

His parents will only be able to look on as their lively boy slowly but inexorably fades.

Ben’s condition has been caused by Niemann-Pick, a rare genetic disorder which affects only 500 children worldwide. It occurs as a result of the build-up of cholesterol in all the body’s organs, including the brain, effectively stopping them from performing their job, causing a progressive loss of mental faculties as well as problems with movement.

‘I don’t know which is harder, that Ben is going to die, or that it will get to the stage where Ben won’t know who I am,’ says Lyndsay, 30, a full-time mother.

‘I don’t want to think about the day that his eyes stop shining; the day I’m caring for Ben – cuddling, feeding and washing him – but the Ben we know isn’t in there any more. I dread the day he won’t smile at us.’

What makes the disease even more cruel is that the pace of deterioration is so unpredictable.

‘We know Ben will lose skills like eating, talking and smiling, but we don’t know when,’ she says. ‘It could be in six months or six years.’

But already over the past year the changes have begun to speed up, explains Andrew, 33, a sales manager.

‘Last summer Ben was able to go to the toilet; he is now incontinent. Two years ago he could run around with his sisters; now he needs the help of a walking frame. He is less responsive than he was. He can still communicate but his speech is slurred.’

Cruel family ties

To make matters worse, the genetic condition might also affect their daughter Lucy, who is 18 months younger than Ben.

Doctors have not yet been able to pinpoint the exact form of gene mutation Ben has. Until they do, they cannot test Lucy – it is a case of watch and wait.

‘At first we thought she’d be fine because she’s older than Ben was when he first developed symptoms, but now we’ve been told it can strike at different ages and she might not have symptoms until she is in her teens,’ says Lyndsay. ‘I’m trying not to think about it.’

Lyndsay had known from early on that there was something wrong with Ben (she has two other daughters, Gemma, 12, and Charlotte, ten, from a previous marriage).

‘Something wasn’t quite as it should be,’ she says. ‘I didn’t know what it was, but as a baby he didn’t feed well, wouldn’t put on weight but had a bloated tummy and was jaundiced. Whenever I mentioned my concerns to a doctor they’d just say: “Oh, it’s a boy thing, he’ll grow out of it.” ‘

‘We were seen as panicky parents,’ adds Andrew. ‘But we were sure something was wrong.

When it came to walking he took his first steps at 17 months, but by two-and-a-half he’d constantly fall over, as if tripping over something that wasn’t there. He always had bruises and cut knees. Again, the doctor just said he was clumsy and generally delayed.’

‘His speech was also slow,’ says Lyndsay. ‘By the time he started primary school, Ben could communicate and put three or four words together but they were quite slurred. His fine motor skills were also very poor. He couldn’t hold pencils.’

Ben’s teachers expressed concern, so the Scotts contacted their local child development centre. After an eight-month wait, they saw an occupational therapist, who referred Ben, then five, to a paediatrician.

When the paediatrician saw Ben seven months later, again the Scotts were told there was nothing to be concerned about, that his development was just a little bit delayed.

Ben’s unforeseen decline

But over the next year Ben fell more and more behind at school. At six, when other kids were reading and writing, Ben still couldn’t hold a pen because his fine motor skills were so poor and he could only recognise the letters B and E. He was also losing his ability to run and had become incontinent.

‘The incontinence was the last straw,’ says Lyndsay. ‘We knew that wasn’t right. Through a fantastic support group called Special Kids, I was advised to get Ben checked out by a neurologist. The paediatrician said there was no need, but we insisted.’

On April 29, Ben met Dr Philip Jardine at Bristol Children’s Hospital and was admitted for scores of tests including an MRI scan, and bone marrow, muscle and skin biopsies. Two weeks later Dr Jardine rang with the results.

‘He said he couldn’t talk over the phone but that we should come and see him as soon as possible,’ says Andrew.

‘The first appointment was short. Dr Jardine explained the tests showed Ben had deposits of cholesterol around his organs caused by Niemann-Pick. Then he said: “Ben will die from this between the ages of 15 and 20.”

‘We were speechless. Finally I asked him if he was sure and he said 99.99 per cent so.’

‘He handed Lyndsay some tissues and I asked for some, too,’ recalls Andrew. ‘We were numb and sat in the car on the way home without talking. How could our seven-year-old have dementia? That’s what old people get.’

There are three forms of Niemann-Pick Disease: Type A, B and C. Each affects the way the body breaks down fat and are caused by genetic mutations passed down from the child’s parents, who must both be carriers of the defective gene but may have no symptoms themselves.

Type A rapidly affects the brain and usually causes death before the age of three. Type B affects the liver, spleen and respiratory system and sufferers can survive into adolescence or adulthood.

Type C, which Ben has, is the most common. Because of a faulty gene, the body doesn’t produce the enzyme needed to break down cholesterol.

The build-up in the organs, including the brain, liver and spleen, causes a massive deterioration, leading to mental and physical problems (unlike adult dementia sufferers, whose problems are largely mental).

Symptoms set in

The Scotts have done all they can to find out more about the condition and what the future holds for Ben. But because it is so rare, it’s hard to gather information.

‘The doctors just don’t know how bad he is,’ says Andrew. ‘Some children develop it at two and live past 15, some get symptoms at 18 and live to 30, some die by the age of four.’

But the condition has a certain pattern – the cholesterol around the brain starts to disrupt the signals to do with movement, affecting coordination.

Ben already falls over a lot and finds it hard to walk. Eventually, he won’t be able to swallow properly and food will get into his lungs, raising the risk of pneumonia, so he will need to be fed through a tube. In some cases, the cholesterol around the liver can cause liver disease.

His memory will start to fade as his brain function deteriorates. Then he will suddenly lose the ability to walk, talk and feed himself. In the final stages the sufferer is immobile and unaware of the world around them.

As with adult dementia, there are currently trials into drugs that might help symptoms, but there is no cure.

‘Right now his symptoms are a bit like he’s drunk a bottle of vodka,’ says Andrew. ‘It’s quite hard work for him to do anything, even very small things. A small walk takes a lot out of him.

‘His memory about people and things is still pretty good. He knows exactly who we are and knows we are going on holiday soon, so every morning he asks: “Are we camping today?”

‘But eating is the area we really need to watch at the moment. He puts food in his mouth but he forgets to chew. We have to rub his mouth to remind him.

‘He also has learning difficulties; he can count to five, or ten on a really good day, but those were things he could do at three or four. And his mobility is much, much worse. When he stands up, we need to remind him to move one foot forward in front of the other.’

The only blessing

The only blessing in all this is that Ben doesn’t understand what’s going on – because of the disease, intellectually he’s never advanced beyond the age of four, and he now attends a school for children with special needs.

But he is a happy child.

‘Most of the time Ben is a very content little boy,’ says Lyndsay. ‘But sometimes he gets frustrated when he can’t do things he used to do. He loves building towers out of wooden blocks, but as he gets older and his skills become less, he’s finding it harder and harder to build the towers; they keep falling down.

‘Other times he’s like a normal little boy. We take him to an adventure park where there’s a log flume water ride and he loves it. He really loves the thrill, the adrenaline. His face lights up just like any other seven-year-old. It’s hard. The other day I was in the supermarket and I had tears streaming down my face. Some days it’s overwhelming.

‘Initially I blamed myself, especially because it was genetic. And I’m trying to come to terms with the fact that I’ll outlive my child. It feels surreal. I have to keep reminding myself, that this is happening to us. It’s like I’m talking about someone else’s life.’

The only practical thing the Scott family can do is raise awareness of the condition so that other families don’t have to wait years for a diagnosis.

‘Having a diagnosis has made a huge difference, it’s meant we can get him all the help he needs,’ says Lyndsay.

The Scotts still get upset thinking about the days he was in a mainstream school, sitting in dirty nappies, unable to take part in what was going on around him. These days they do all they can to make the best of every day.

‘I find myself constantly looking at his face when he smiles, so I can remember him that way,’ says – Lyndsay.

‘As a mum, you could be up all night with your six-month-old, but one smile from your baby and everything is forgiven. I want to remember every one of Ben’s smiles. I want to remember that in his head, Ben is happy. Today is the best he is going to be, and we have to love every minute. Every day is about making memories of the time we have.’

And with that, Andrew strokes his darling boy’s legs and takes another photograph.

For more information contact the Niemann-Pick Support Group (UK), 0191 415 0693 www.niemannpick.org.uk.

Putting Drug Development In Patients’ Hands

August 5, 2008 by  
Filed under Virtual BioTechs

An Entrepreneur Stricken With Cancer Sets Up Firm To Develop ‘Virtual’ Biotechs
By AMY DOCKSER MARCUS July 29, 2008; Page D1

Jay M. Tenenbaum became a multimillionaire in the Internet boom of the late 1990s. But it wasn’t until he was diagnosed with a lethal cancer that he found his calling as an Internet entrepreneur.

Dr. Tenenbaum learned in 1998 that he had melanoma, the most serious kind of skin cancer. He underwent surgery and took an experimental vaccine for a year. Then, nearly five years ago, the cancer returned, having spread to his liver. "That’s when I started looking at my mortality seriously," says the 65-year-old from Portola Valley, Calif.

Frustrated with his treatment options, Dr. Tenenbaum began investigating other potential therapies. He found dozens of patient-advocacy organizations dedicated to melanoma that raised money and supported scientific research. They "all had good ideas," he says, "but no one had put the different pieces together in the right way that would let them make progress in finding a drug in the lifetime of a patient."

So he tapped his own Internet savvy — and his connections — to create a company aimed at helping patients develop new therapies faster and cheaper for less common diseases, like melanoma, that often don’t attract major pharmaceutical company research funding. He set up his new company, called CollabRx, with $2 million he had available and is trying to raise $3 million more from family, friends and private investors.

[Jay Tenenbaum]
Thor Swift for The Wall Street Journal
Jay Tenenbaum started CollabRx to help patients hasten drug development.

Dr. Tenenbaum’s idea taps into the recent phenomenon of patient-supported research — a trend largely driven by people wealthy enough to help fund drug-discovery projects and who are affected by rare or overlooked diseases.

The Myelin Repair Foundation, founded by a patient with multiple sclerosis, set up a team of researchers to come up with promising drug leads. After spending $13 million over four years, the foundation will present its two best prospects to drug companies in coming months in the hopes of getting one of them to develop the drugs further. And the Cystic Fibrosis Foundation, started by a group of parents who had children with the disease, recently announced that a drug it is paying a biotech company to develop showed promising results in an ongoing trial. The foundation says its investment in the drug so far exceeds $75 million.

CollabRx aims to expand patient-funded research further by connecting individuals or small numbers of patients with the tools and services they need. Each CollabRx client is assigned a project manager, a specialist who works with patients to devise a research strategy, interpret the results and later steer any promising prospects toward development of possible treatments.

CollabRx calls such integrated projects virtual biotechs because they aim to replicate many of the steps typically taken as part of a pharmaceutical or biotech company’s search for a new drug. As the number of private labs available to do sophisticated research grows, many parts of the drug-development process can now be contracted separately. Researchers in various locations can share information and material by means of a Web-based network created by CollabRx software engineers.

Management Fees

CollabRx’s fees vary depending on the scope of a project. But Dr. Tenenbaum says he expects to charge most clients a management fee of 10% of a project’s budget and to receive a 20% share of any intellectual property that emerges. Drug screens, clinical trials, and the costs of other contracted services are paid for by the clients.


Dr. Tenenbaum says patients can get started on a project with as little as $50,000 to $100,000. Sums like that, for example, could fund the creation of a molecular profile of a tumor to try to predict what combination of already approved drugs might be effective. If results proved promising, more money could be raised to set up a full-blown virtual biotech — with a budget in the millions of dollars — that might test cocktails of therapies in animal models and try grouping patients into subtypes to better tailor treatments for them, among other projects.

Bonnie J. Addario, a former oil-company executive in San Francisco, is a lung-cancer survivor. When she first started thinking about how to make a difference, she figured, "I’ll run a gala and a golf tournament, raise money for research, and that will be it." Mrs. Addario, 60, raised $800,000 through a foundation she set up in 2006. She distributed the money to a number of researchers, and then realized, "there are a lot of wonderful people doing great work, but lung-cancer survival rates [of 15.5% after five years] haven’t changed for 40 years. Why is that?"

To find answers, Mrs. Addario and her husband, along with David M. Jablons, her surgeon from the University of California, San Francisco, put together a two-day conference last fall of lung-cancer researchers from major institutions around the world. She says the group identified a number of problems that hinder progress toward a cure. Among them: Researchers didn’t know what others were doing, tissue and blood specimens needed for experiments weren’t centrally located or shared, and the findings of experiments weren’t integrated to help assess what the key priorities should be.

Mrs. Addario started a new organization, the Addario Lung Cancer Medical Institute, and hired CollabRx to address some of these issues. The company is helping the institute build a virtual specimen bank where researchers participating in the project can share patient specimens and establish joint standards for collecting future specimens. Using the CollabRx Web-based network, the researchers can share research and ideas, and quickly reprioritize projects as new information comes up. Mrs. Addario says the institute expects to spend at least $5 million over the next year to set up the virtual biotech, fund researchers and establish the specimen bank.

It’s far too early to tell whether CollabRx’s approach will be more successful at finding new drugs cheaper or faster than the traditional methods of drug and biotech companies, a challenge acknowledged by scientists who target faster cures. "We’re not discovering drugs slowly just because of a faulty business model," says John Wilbanks, executive director of Science Commons, a nonprofit in Cambridge, Mass., that seeks to make research more effective by encouraging more open access to scientific data. "We don’t understand so many things about toxicity in the human body. It’s hard because it’s hard," says Mr. Wilbanks, who works with Dr. Tenenbaum on a separate project. On average, the pharmaceutical industry spends about $1 billion over 17 years to bring a new drug to market.

CollabRx’s approach in some respects also goes against the cultural grain of scientific research. In order for academic researchers to get ahead at universities, they must be first to publish breakthrough findings. This competitive culture deters scientists from sharing information, and could make it difficult for CollabRx to get researchers to work together.

The Internet culture that drives CollabRx encourages collaboration, says Christopher P. Austin, director of the Chemical Genomics Center of the National Institutes of Health. "And unlike the Internet, where people were maniacal about sharing stuff, biomedical scientists are exactly the opposite," he says. "You have to drag their data from their cold dead fingers. They do not share." Dr. Austin is testing CollabRx’s network with one of his lab’s projects that seeks to develop therapies for a rare disease.

Internet Background

Dr. Tenenbaum, who has a Ph.D. from Stanford University in electrical engineering and computer science, was deeply involved in the Internet boom of the 1990s. He started a number of Web companies that helped pioneer the use of e-commerce. His most lucrative foray was as chief scientist and a board member of Commerce One Inc., which developed technology enabling the computer systems of big businesses to interact more readily. Dr. Tenenbaum, who goes by the nickname Marty, left Commerce One in 2002 as the company was struggling amid the tech bust early this decade.

Dr. Tenenbaum is engaged in another project with several partners that also borrows from the Internet culture — creating a nonprofit marketplace for data, materials, resources and services needed for studying and treating disease, to be called Health Commons. The partners, which also include Science Commons, the Public Library of Science, and CommerceNet, plan to set up a site where people and companies in the life sciences can go to buy and sell goods and services.

Dr. Tenenbaum says that if Health Commons is successful, it could help CollabRx locate resources for its virtual biotechs. Even individual patients, should they want to pursue research and drug development on their own, could find information and services at the site, he says. (For a summary of the Health Commons project, go to http://sciencecommons.org/projects/healthcommons/.)

Chris and Hugh Hempel of Reno, Nev., last fall met with Dr. Tenenbaum a few weeks after learning that their 4-year-old twin daughters, Addi and Cassi, had been diagnosed with Niemann-Pick Type C, a genetic neurodegenerative disorder that usually is fatal by the age of 20. The Hempels joined with a group of parents to fund SOAR-NPC, a virtual biotech CollabRx set up.

The group decided that the fastest way to help the children would be to focus on a combination therapy of already approved drugs and other compounds that could prevent or significantly delay the onset and progression of NPC. Mrs. Hempel, who runs a public-relations firm, says she and her husband recently raised $500,000 at a gala event in Reno that will help fund the virtual biotech, whose total budget is $1.3 million for the first year. The project currently is testing a number of drug candidates at an NIH-run facility. Later this year, the first human observational study will start.

Melanoma Study

CollabRx also is helping to coordinate a melanoma study at the John Wayne Cancer Institute in Santa Monica, Calif., which received a grant from the Melanoma Research Alliance. The project, with a budget of $1 million over three years, is using genomic technologies to test melanoma tumors collected by the institute over the past two decades to find drugs that might work on clusters of individuals whose tumors exhibit certain similarities.

The melanoma alliance, set up with funding from Apollo Advisors founding partner Leon D. Black and his wife, Debra, and FasterCures, an organization created by financier Michael Milken, are also discussing a larger project with CollabRx to set up a melanoma virtual biotech. That project would test various melanoma cell lines against existing drugs and drug combinations with the aim of advancing promising prospects to clinical trials. Gregory C. Simon, president of FasterCures, says he sees the melanoma virtual biotech as a model that could be useful to other advocacy groups with which FasterCures works.

It is a project that Dr. Tenenbaum is following closely, not only in his role at CollabRx but also as someone who might benefit from any potential therapies that emerge. Mr. Tenebaum has had four surgeries to remove suspicious nodules since his cancer returned, and he gets scans every few months. Right now, there are no signs of the cancer. "But with melanoma," he says, "that can change overnight."

He plans to contribute funding for the melanoma virtual biotech out of his own pocket. Eventually, Dr. Tenenbaum says he plans to pay to have his own tumor cells tested with whatever drug combinations the virtual biotech finds are promising.

"The fact that there is no therapy right now that works in general for melanoma patients doesn’t mean that there is no therapy that works on selected patients," Dr. Tenenbaum says. "That is where CollabRx comes in. I want to have that information in hand, just in case I ever need it."

Write to Amy Dockser Marcus at amy.marcus@wsj.com

PET Neuroimaging of Addi and Cassi’s Brains at Children’s Hospital Michigan

August 4, 2008 by  
Filed under Videos

A Look Inside The Brain – Scans Of Twins, Addi and Cassi from Addi & Cassi Hempel on Vimeo.

A video of our trip to Detroit to visit Children’s Hospital Michigan to have PET neuroimaging brain scans done on our four year old identical twins, Addi and Cassi. These scans have not been done before on children with Niemann Pick Type C disease, also known as the “Childhood Alzheimer’s.” We hope these brain PET scans lead to new insights into neurological diseases of all types.