Stem cell researchers inch toward treatment for Huntington’s Disease

June 17, 2010 | Susan Valot | KPCC

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Courtesy of Leslie Thompson/UC Irvine

This photo shows two mice with Huntington's Disease symptoms. The one on the left was not treated. The one on the right was injected with neural stem cells, which seem to protect neurons and neural pathways in the brain.

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People with Huntington’s disease face an awful future - perhaps 20 years as it slowly strips away brain cells. But there’s a chance that in the next 20 years, researchers at UC Irvine could develop treatments that could arrest Huntington’s – and other brain and nervous systems disorders – thanks in part to a girl from Fountain Valley.

Emily Krull of Fountain Valley was a normal, brown-haired little girl. Up until sixth grade, she got good grades and made the honor roll. But seventh grade hit and Emily’s grades plummeted. She became depressed and hard to motivate.

Her parents had adopted Emily when she was little; they figured whatever was going on was just a teenage phase. But then Emily started blinking a lot and losing her balance, like she was drunk.

Her mom, Carla Krull, says Emily’s school even wanted to give her a drug test at her prom.

"And when she went to Knott’s Scary Farm, they wanted to alcohol test her," Carla Krull remembers. "And imagine, you’re with your friends or your boyfriend and how the humiliation of having to be drug tested, and they’re not listening to you when you say, 'I'm not drunk.'"

Emily’s parents knew something was wrong. They just didn’t know what.

Eight neurologists later, they figured it out: Huntington’s Disease – the fatal genetic brain disorder. Brain cells stop communicating and die off.

Folk singer Woody Guthrie died of Huntington’s. So did Emily Krull, last October at the age of 21.

But Carla Krull says before she died, Emily walked into a lab at UC Irvine and donated a small chunk of skin. From Emily’s skin, researchers are developing stem cells that might someday help lead to a cure for Huntington’s.

"It was a real exciting day for her," Carla Krull said. "It was like a war wound. It’s like the movie, 'Twilight,' the vampires? It was like her vampire bite. Yeah, she was very excited about it."

The lab that Emily walked into is run by Leslie Thompson, who’s studying possible stem cell treatments for Huntington’s Disease, which is in some ways similar to Parkinson’s or Alzheimer’s disease. The brain’s pathways are blocked by clumps of protein.

"The cells don’t communicate well. They don’t turn over. They don’t clear out garbage, like the cell debris. They can’t clear it as well," Thompson said. "They can’t create the appropriate proteins, the correct signals between the neuron and the brain. They can’t make enough of them that they would normally need to make."

Similarities in Huntington’s, Parkinson’s, Alzheimer’s and Lou Gehrig’s disease mean there’s overlap in research. A breakthrough in Huntington’s could help move along research into the other brain-robbing diseases.

With Huntington’s, Thompson says it’s a little bit easier because scientists know it’s caused by a single genetic mutation.

"Which offers a huge advantage for this kind of work, because you know who has it – you know exactly what individuals have it, you know when they become symptomatic or who’s going to become symptomatic so you can start treatment early. You can create lines that all have the genetic mutation in them," said Thompson.

If one of your parents had Huntington’s – which usually strikes between the ages of 35 and 44 – then you have a 50 percent chance of getting it.

Thompson is working on creating models that use Huntington’s Disease stem cell lines so researchers can more quickly test which drugs work.

She’s also looking at how mice with Huntington’s Disease react when neural stem cells are injected into their brains.

"The stem cells produce very protective factors to the brain and so if we transplant these cells, certain types of cells, into the brain of, say an HD [Huntington's Disease] mouse, which is what we’re doing right now, they sort of nurse existing neurons that are there and keep them sort of protected," Thompson said.

That suggests a treatment someday that could stop symptoms from progressing or prevent them in the first place. But Thompson says there’s still a lot they don’t know.

"What are some of the initial triggers?" she said. "We know a lot about some of the things that happen in the neuron. But we’re still at the phase of trying to prevent some of the really early steps and you know, how to get a neuron that’s sick to not be sick, basically."

Thompson predicts tests on stem cell-based therapies for Huntington’s Disease could start in the next five to 15 years. That’s something that gives hope to Emily Krull’s parents.

"I feel that she was meant for us because we would carry this on. And we’re determined to carry this on until we get a cure."

And, says mom Carla Krull, if Emily could see the progress that’s been made in the past couple of years toward finding a treatment for Huntington’s Disease, Emily would be smiling.


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Matt

2 months, 3 weeks ago

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Why the next five to 15 years? The $ is there....why are all these discoveries in every disease always pushed out in time? Why not just move everything to china, india, russia, etc where highly educated people will be more than happy to get results sooner

Omar

2 months, 3 weeks ago

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Honestly Matt i am in complete agreement with you, it is pathetic how in the western society they take their sweet time developing little breaks while millions of people continue to suffer at the hands of such genetic diseases. I agree with you completely when it comes to transfering all this research to the above stated countries where many can agree the doctors and scientist are much more educated and equiped and motivated to cure such cases. It is a shame that over here money is the only thing of importance, while once again mentioning millions of people have to suffer for something they had no say or hand in at such an innocent age.

Pojoe

2 months, 3 weeks ago

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Third and second world countries are neither better educated, nor better equipped to deal with these complex problems. Korea put back stem cell research with cheating scientists who falsified data. They are not trustworthy in any sense of the word. Good science takes time, especially pioneering science. The reason it takes the time it does is because things are in the discovery phase, and these discoveries are only just behind the technology to be discovered. My son's are at risk for HD also, and I want treatments as soon as possible, but realistically, cracking open their skull in the hands of Chinese doctors is a ridiculous proposition. They are as dangerous as HD itself.

Adam

2 months, 3 weeks ago

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Your points are all valid.
Research requires time and $$$ as well as people both scientists and those with the disease.
New treatments do not always work or they do not work as hoped for.
Also, for the benefits any new treatment might promise, there will be risks and side effects some of which are unknown.
Each person needs to decided what is acceptable.
5-15 years is a broad range and is the estimate given by one research scientist. Other scientists might think differently
For my friend with HD symptoms, it feels like a long time to wait because you live with the disease everyday
For others without symptoms, 5-15 years give them hope.
The whole thing is complex and many factors are involved.
Even though there will be those who try to take advantage of people's sufferings, I choose to find,support and encourage those who are truly care and want to help.
Ultimately, I am grateful to people like Emily Krull and Leslie Thompson for their sacrifice and contributions.
Many will never hear or remember their names but their gifts will endure as part of the cure

Sharon

2 months, 3 weeks ago

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There actually is research going on all over the world, not just in the United States. And unlike much scientific researchers, these researchers are all actively collaborating!

Sharon

2 months, 3 weeks ago

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There actually is research going on all over the world, not just in the United States. And unlike much scientific researchers, these researchers are all actively collaborating! I just hope that a cure or a way to slow the progression will come in time for my 24-year-old son who has early symptoms of HD. It's too late for his father and his uncles, and it's something we've been hoping for ever since the marker for the gene was discovered about 20 years ago. We have to remember and hope, though, that tomorrow--or any other day--could be THE day that makes the defining difference!

Renee Middleton

2 months, 2 weeks ago

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I hate this diease..Everyday I watch my husband disappear. I pray they find a cure SOON.....

samantha

2 months, 2 weeks ago

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Renee, I'm in the same boat, my heart goes out to you.....Samantha

Nicole

2 months, 2 weeks ago

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Published online 22 June 2010 | Nature 465, 997 (2010) | doi:10.1038/465997a

News
Strange lesions after stem-cell therapy

Unproven treatment results in mysterious masses.

David Cyranoski

In a stark reminder that stem-cell therapy is uncharted territory, a stem-cell transplant given to a patient in Thailand who had kidney disease resulted in the development of cellular masses not previously reported. The lesions, described in a paper published online on 17 June in the Journal of the American Society of Nephrology, were not directly linked to the patient's subsequent death (D. Thirabanjasak et al. J. Am. Soc. Nephrol. doi:10.1681/ASN.2009111156; 2010).

With hundreds of poorly regulated clinics that offer unproven stem-cell therapies now running, notably in China and Thailand, the episode is a warning to patients who may be considering such treatment.

The patient had lupus nephritis, in which the immune system attacks the kidneys. In 2006, she underwent a procedure at a private clinic in which her own haematopoietic stem cells — which can develop into any type of blood cell — were injected into her kidneys. Details of the clinic and the rationale behind the treatment have not been released.

“She didn’t get any better from stem cells, we can say that.”

Haematopoietic stem cells have been used to treat lupus nephritis with some reports of success. But they are usually injected into the bloodstream, not the kidney,­ in an attempt to 'reset' the immune system.

Six months later, the patient complained of pain and blood in the urine. Imaging studies revealed a four-centimetre mass on her left kidney and smaller masses in the kidney, liver and adrenal gland. Doctors at Chulalongkorn University in Bangkok removed the kidney, believing a malignant tumour to be present. But further analysis showed that it was something else.

"I had never seen anything like it," says Paul Thorner, a pathologist at the Hospital for Sick Children in Toronto, Canada, who has a joint position at Chulalongkorn University and was a co-author on the paper. Thorner coined a term — angiomyeloproliferative — to describe the proliferation of blood-vessel and bone-marrow cells the team found.

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Patients are undergoing other experimental stem-cell therapies, but there is usually little follow-up to establish safety or efficacy. In one case reported last year, a boy treated with fetal stem cells at a Russian clinic developed tumours in his brain and spinal cord. In the Thai case, no post-mortem was carried out, as far as Thorner is aware, so his team could work only on the removed kidney. It is not known whether the smaller masses were linked to the main mass, or what would have happened had the patient not died from other complications. "She didn't get any better from stem cells, we can say that," says Thorner, who may try to reproduce the masses in animal experiments.

Julie

2 months, 2 weeks ago

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I knew Emily and her parents. She never had a chance with H.D. But, she had the best possible care here in Orange County, with Dr. Leslie Thompson and Dr. Neal Hermanowicz, M.D., etal. We need to keep an open mind about stem-cell research, but let's not rule it out completely.
In my family, we never knew of any previous generations who had struggled with this disease. It took a long time before someone was able to diagnose my brother's balance and jerky movements as H.D. He, too, was thought to be drunk, and even ended up in jail a couple of times, due to his behavior. He died because no one would take him into a long-term care facility once they found he had been diagnosed with H,D., and no one knew how to help him.
This current generation is going to see a huge explosion in the numbers of H.D. patients , due to the fact that many families never knew it was present in the previous generation. Anyone who had kids...now they're all at-risk. Thanks to the genetic testing now available, we can tell someone with almost 100% certainty, that they're either positive or negative for the gene. But, not everyone is going to adopt, have in-vitro-fertilization, or elect not to have kids. Not only should we be doing research, we should be making a better effort at educating at-risk individuals, to discourage them from having children of their own. It is possible to wipe this disease out in the next generation this way.
Right now when people hear the initials "H.D.", they think we're defining "high definition" television! Very few people understand the permanent disability part of the disease, and persons having the disease are discrimininated against in work places, disability claims, and insurance issues.
Please join those clinical drug trials that are being offered in your area to make the research go more quickly, and to present enough numbers to validate the results. P.S. I also have a "snake bite" on my forearm like Emily did.

beverly hills therapist

2 months, 1 week ago

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That is so sad that she live such a short life and I hope that she lived her life to the max. She did a great thing by donating a bit of her skin for research. I got to admit I am still conflicted about the whole stem cell research.

Leslie

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