neurodegenerative disorder

California agency invests $4 million in stem cell treatment for Parkinson’s Disease

/ Esteban Cortez / 2 Comments

The California Institute for Regenerative Medicine (CIRM) is investing $4 million in a late-stage preclinical project by Ryne Bio aiming to improve treatment for Idiopathic Parkinson’s disease (PD).

PD is characterized by a loss of dopamine producing neurons that result in motor symptoms, such as dyskinesias (involuntary, erratic, writhing movements of the face, arms, legs or trunk) and non-motor effects such as dementia, depression and sleep disorders.

PD is the second-most common neurodegenerative disease after Alzheimer’s disease affecting approximately 1 million people in the U.S. In California, it is estimated that 116,900 people live with PD, representing the highest number of people with the disease in the country.

At its early stages, PD can be treated with medication such as Levodopa to treat symptoms but these become less effective as the disease progresses.

The proposed stem cell therapy in this project offers the potential to restore dopamine neurons, which play a role in many important body functions, including movement and memory.

Investigators at Ryne Bio are aiming to deliver dopamine producing cells to replace the lost neurons to the brain of Parkinson’s disease patients to restore/improve motor function.

The current grant is being funded to conduct Investigational New Drug (IND) enabling, nonclinical safety studies per the US Food and Drug Administration (FDA) Guidance. The IND is the authorization needed to begin a clinical trial in Parkinson’s patients.

CIRM has a vested interest in seeing this therapy succeed. To date, CIRM has invested more than $59 million in helping research for Parkinson’s disease progress from a basic or Discovery level through clinical trials.

Rhythmic brain circuits built from stem cells

/ Todd Dubnicoff / Leave a comment

The TV commercial is nearly 20 years old but I remember it vividly: a couple is driving down a street when they suddenly realize the music on their tape deck is in sync with the repetitive activity on the street. From the guy casually dribbling a basketball to people walking along the sidewalk to the delivery people passing packages out of their truck, everything and everyone is moving rhythmically to the beat.

The ending tag line was, “Sometimes things just come together,” which is quite true. Many of our basic daily activities like breathing and walking just come together as a result of repetitive movement. It’s easy to take them for granted but those rhythmic patterns ultimately rely on very intricate, interconnected signals between nerve cells, also called neurons, in the brain and spinal cord.

Circuitoids: a neural network in a lab dish

A CIRM-funded study published yesterday in eLife by Salk Institute scientists reports on a method to mimic these repetitive signals in a lab dish using neurons grown from embryonic stem cells. This novel cell circuitry system gives the researchers a tool for gaining new insights into neurodegenerative diseases, like Parkinson’s and ALS, and may even provide a means to fix neurons damaged by injury or disease.

The researchers changed or specialized mouse embryonic stem cells into neurons that either stimulate nerve signals, called excitatory neurons, or neurons that block nerve signals, called inhibitory neurons. Growing these groups of cells together led to spontaneous rhythmic nerve signals. These clumps of cells containing about 50,000 neurons each were dubbed circuitoids by the team.

pfaff-circutoid-cropped

Confocal microscope immunofluorescent image of a spinal cord neural circuit made entirely from stem cells and termed a “circuitoid.” Credit: Salk Institute.

Making neural networks dance to a different beat

A video produced by the Salk Institute (see below), shows some fascinating microscopy visualizations of these circuitoids’ repetitive signals. In the video, team leader Samuel Pfaff explains that changing the ratio of excitatory vs inhibitory neurons had noticeable effects on the rhythm of the nerve impulses:

“What we were able to do is combine different ratios of cell types and study properties of the rhythmicity of the circuitoid. And that rhythmicity could be very tightly control depending on the cellular composition of the neural networks that we were forming. So we could regulate the speed [of the rhythmicity] which is kind of equivalent to how fast you’re walking.”

It’s possible that the actual neural networks in our brains have the flexibility to vary the ratio of the active excitatory to inhibitory neurons as a way to allow adjustments in the body’s repetitive movements. But the complexity of those networks in the human brain are staggering which is why these circuitoids could help:

Samuel Pfaff. (Salk Institute)

Samuel Pfaff. (Salk Institute)

“It’s still very difficult to contemplate how large groups of neurons with literally billions if not trillions of connections take information and process it,” says Pfaff in a press release. “But we think that developing this kind of simple circuitry in a dish will allow us to extract some of the principles of how real brain circuits operate. With that basic information maybe we can begin to understand how things go awry in disease.”

Using stem cells to fix bad behavior in the brain

/ Kevin McCormack / 2 Comments

 

finkbeiner-skibinski-16x9-13

Gladstone Institutes Steven Finkbeiner and Gaia Skibinski: Photo courtesy Chris Goodfellow, Gladstone Institutes

Diseases of the brain have many different names, from Alzheimer’s and Parkinson’s to ALS and Huntington’s, but they often have similar causes. Researchers at the Gladstone Institutes in San Francisco are using that knowledge to try and find an approach that might be effective against all of these diseases. In a new CIRM-funded study, they have identified one protein that could help do just that.

Many neurodegenerative diseases are caused by faulty proteins, which start to pile up and cause damage to neurons, the brain cells that are responsible for processing and transmitting information. Ultimately, the misbehaving proteins cause those cells to die.

The researchers at the Gladstone found a way to counter this destructive process by using a protein called Nrf2. They used neurons from humans (made from induced pluripotent stem cells – iPSCs – hence the stem cell connection here) and rats. They then tested these cells in neurons that were engineered to have two different kinds of mutations found in  Parkinson’s disease (PD) plus the Nrf2 protein.

Using a unique microscope they designed especially for this study, they were able to track those transplanted neurons and monitor what happened to them over the course of a week.

The neurons that expressed Nrf2 were able to render one of those PD-causing proteins harmless, and remove the other two mutant proteins from the brain cells.

In a news release to accompany the study in The Proceedings of the National Academy of Sciences, first author Gaia Skibinski, said Nrf2 acts like a house-cleaner brought in to tidy up a mess:

“Nrf2 coordinates a whole program of gene expression, but we didn’t know how important it was for regulating protein levels until now. Over-expressing Nrf2 in cellular models of Parkinson’s disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we’ve found.”

Steven Finkbeiner, the senior author on the study and a Gladstone professor, said this model doesn’t just hold out hope for treating Parkinson’s disease but for treating a number of other neurodegenerative problems:

“I am very enthusiastic about this strategy for treating neurodegenerative diseases. We’ve tested Nrf2 in models of Huntington’s disease, Parkinson’s disease, and ALS, and it is the most protective thing we’ve ever found. Based on the magnitude and the breadth of the effect, we really want to understand Nrf2 and its role in protein regulation better.”

The next step is to use this deeper understanding to identify other proteins that interact with Nrf2, and potentially find ways to harness that knowledge for new therapies for neurodegenerative disorders.

CREATE-ing tools that deliver genes past the blood-brain barrier

/ Karen Ring / Leave a comment

Your brain has a natural defense that protects it from infection and harm, it’s called the blood-brain barrier (BBB). The BBB is a selectively permeable layer of tightly packed cells that separates the blood in your circulatory system from your brain. Only certain nutrients, hormones, and molecules can pass through the BBB into the brain, while harmful chemicals and infection-causing bacteria are stopped at the border.

This ultimate defense barrier has its downsides though. It’s estimated that 98% of potential drugs that could treat brain diseases cannot pass through the BBB. Only some drug compounds that are very small in size or are fat-soluble can get through. Clearly, getting drugs and therapies past the BBB is a huge conundrum that remains to be solved.

Penetrating the Impenetrable

However, a CIRM-funded study published today in Nature Biotechnology has developed a delivery tool that can bypass the BBB and deliver genes into the brain. Scientists from Caltech and Stanford University used an innocuous virus called an adeno-associated virus (AAV) to transport genetic material through the BBB into brain cells.

Viral delivery is a common method to target and deliver genes or drugs to specific tissues or cells in the body. But with the brain and its impenetrable barrier, scientists are forced to surgically inject the virus into specific areas of the brain, which limits the areas of the brain that get treatment, not to mention the very invasive and potentially damaging nature of the surgery itself. For diseases that affect multiple areas in the brain, like Huntington’s and Alzheimer’s disease, direct injection methods are not likely to be effective. Thus, a virus that can slip past the BBB and reach all parts of the brain would be an idea tool for delivering drugs and therapies.

And that’s just what this new study accomplished. Scientists developed a method for generating modified AAVs that can be injected into the circulatory system of mice, pass through the BBB, and deliver genetic material into the brain.

They devised a viral selection assay called CREATE (which stands for Cre Recombinase-based AAV Targeted Evolution). Using CREATE, they tested millions of AAVs that all had slight differences in the genetic composition of their capsid, or the protein shell of the virus that protects the viruses’ genetic material. They tested these modified viruses in mice to see which ones were able to cross the BBB and deliver genes to support cells in the brain called astrocytes. For more details on how the science of CREATE works, you can read an eloquent summary in the Caltech press release.

A Virus that Makes Your Brain Glow Green

After optimizing their viral selection assay, the scientists were able to identify one AAV in particular, AAV-PHP.B, that was exceptionally good at getting past the BBB and targeting astrocytes in the mouse brain.

Lead author on the study, Ben Deverman, explained: “By figuring out a way to get genes across the blood-brain barrier, we are able to deliver them throughout the adult brain with high efficiency.”

They used AAV-PHP.B and AAV9 (which they knew could pass the BBB and infect brain cells) to transport a gene that codes for green fluorescent protein (GFP) into the mouse brain. After injecting mice with both viruses containing GFP, they saw that both viruses were able to make most of the cells in the brain glow green, confirming that they successfully delivered the GFP gene. When they compared the potency of AAV-PHP.B to the AAV9 virus, they saw that AAV-PHP.B was 40 times more efficient in delivering genes to the brain and spinal cord.

sing a new selection method, Caltech researchers have evolved the protein shell of a harmless virus, AAV9, so that it can more efficiently cross the blood brain barrier and deliver genes, such as the green fluorescent protein (GFP), to cells throughout the central nervous system. Here, GFP expression in naturally occurring AAV9 (left) can be seen distributed sparsely throughout the brain. The modified vector, AAV-PHP.B (right), provides more efficient GFP expression. Credit: Ben Deverman and the Gradinaru laboratory/Caltech - See more at: http://www.caltech.edu/news/delivering-genes-across-blood-brain-barrier-49679#sthash.BDu7OfC8.dpuf

Newly “CREATEd” AAV-PHP.B (right) is better at delivering the GFP gene to the brain than AAV9 (left). Credit: Ben Deverman.

“What provides most of AAV-PHP.B’s benefit is its increased ability to get through the vasculature into the brain,” said Ben Deverman. “Once there, many AAVs, including AAV9 are quite good at delivering genes to neurons and glia.”

Senior author on the study, Viviana Gradinaru at Caltech, elaborated: “We could see that AAV-PHP.B was expressed throughout the adult central nervous system with high efficiency in most cell types.”

Not only that, but using a neat technique called PARS CLARITY that Gradinaru developed in her lab, which makes tissues and organs transparent, the scientists were able to see the full reach of the AAV-PHP.B virus. They saw green cells in other organs and in the peripheral nerves, thus showing that AAV-PHP.B works in other parts of the body, not just the brain.

But just because AAV-PHP.B is effective in mice doesn’t mean it works well in humans. To address this question, the authors tested AAV-PHP.B in human neurons and astrocytes derived from human induced pluripotent stem cells (iPS cells). Sergiu Pasca, a collaborator from Stanford and author on the study, told the Stem Cellar:

Sergiu Pasca

Sergiu Pasca

“We have also tested the new AAV variant (AAV-PHP.B) in a human 3D cerebral cortex model developed from human iPS cells and have shown that it transduces human neurons and astrocytes more efficiently than does AAV9 demonstrating the potential for biomedical applications.”

An easier way to deliver genes across the BBB

This study provides a new way to cross the BBB and deliver genes and potential therapies that could treat a laundry list of degenerative brain diseases.

This is only the beginning for this new technology. According to the Caltech press release, the study’s authors have future plans for the AAV-PHP.B virus:

“The researchers hope to begin testing AAV-PHP.B’s ability to deliver potentially therapeutic genes in disease models. They are also working to further evolve the virus to make even better performing variants and to produce variants that target certain cell types with more specificity.”

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New Stem Cell Treatment for ALS May Slow Disease Progression

/ Karen Ring / 30 Comments

Exciting news was published this week that will give patients suffering from ALS, also known as Lou Gehrig’s disease, something to cheer about. The journal JAMA Neurology reported that a new stem cell treatment was successful in slowing disease progression in a small group of ALS patients in a Phase 2 clinical trial.

This is big news for a fatal, incurable disease that is well known for its progressive, degenerating effects on nerve cells in the brain and spinal cord. We’ve written about ALS a lot in the Stem Cellar, so if you want more background on the disease, read our “Progress to a Cure for ALS” blog.

A patient’s own stem cells can help

The stem cell therapy involves extracting mesenchymal stem cells from the bone marrow of ALS patients. These stem cells are then manipulated in culture into cells that secrete a growth factor called NeuroTrophic Factor (NTF), which helps keep nerve cells in the brain and spinal cord healthy and alive. The NTF-secreting stem cells (called NurOwn cells) are then transplanted back into the same ALS patient (making this an autologous stem cell therapy) by injection into either the spinal fluid or the muscles.

logoThe NurOwn method was developed by BrainStorm Cell Therapeutics, a biotech company based in the US and Israel. Clinical trials to test the safety and efficacy of NurOwn stem cells began in 2011 at the Hadassah Medical Organization (HMO). So far, 26 patients have participated in the trials both in the US and in Israel.

According to the JAMA publication, patients were monitored 3 months before and 6 months after they received stem cell transplants and 6 months after. Twelve of the 26 patients participated in an early stage of the trial (phase 1/2) to test the safety and tolerability of the stem cell therapy. The other 14 patients participated in a later stage (phase 2a), dose-escalating study where their modified stem cells were injected into both their spinal fluid and muscles. Following the treatment, the scientists looked at the safety profile of the transplanted stem cells and for signs of clinical improvement in patients such as their ease of breathing or ability to control their muscle movement.

Stem cell treatment is effective in most ALS patients

Results from the clinical trial showed that a majority of the patients benefitted from the NurOwn stem cell therapy. HMO Principle scientist and senior author on the study, Dr. Dimitrios Karussis, explained:

Dr. Dimitrios Karussis (Image credit: Israel21c)

Dimitrios Karussis (Israel21c)

“The results are very encouraging.  Close to 90% of patients who were injected intrathecally through the spinal cord fluid were regarded as responders to the treatment either in terms of their respiratory function or their motor disability.  Almost all of the patients injected in this way showed less progression and some even improved in their respiratory functions or their motor functions.”

A PRNewswire press release covering this study called the stem cell therapy the “first-of-its-kind treatment for treating neurodegenerative diseases.”

Not a cure just yet

This stem cell therapy will need to be tested in more patients before the it can be determined truly effective in slowing progression of ALS. And Dr. Karussis was quick to note that the NurOwn stem cell therapy isn’t a cure for ALS, but rather an early-stage therapy that will provide significant benefit to patients by slowing disease progression.

“I am optimistic that within the foreseeable future, we may provide a treatment to ALS patients that can slow down or stop the progression. I believe we are in the early stages of something new and revolutionary with this harvested stem cell infusion therapy.  While this is absolutely by no means a cure, it is the first step in a long process in that direction.  I see this treatment as being potentially one of the major future tools to treat degenerative diseases of the brain and spinal cord, in general.”

Other stem cell treatments for ALS in the works

A single stem cell therapy that could treat multiple neurodegenerative diseases would be extremely valuable to patients and doctors. However, it’s not clear that the “one ring to rule them all” scenario (couldn’t help making a Lord of the Rings reference) will play out well for all diseases that affect the brain and spinal cord. Luckily, Dr. Karussis and Brainstem Cell Therapeutics are not the only ones pursuing stem cell therapies for ALS.

Clive Svendsen has been on a 15-year quest to develop an ALS therapy

Clive Svendsen

CIRM is currently funding 21 studies (a total of $56.6 million) that use stem cells to either study ALS or to develop therapies to treat the disease. We wrote about one recent study by Clive Svendsen at Cedars Sinai which is using a combination of gene therapy and brain stem cells to deliver growth factors to protect nerve cells in the brain and spinal cord of ALS patients. Currently, Svendsen and his team are in the latter stages of research and hope to apply for FDA approval to test their therapy in patients in the near future. Svendsen told CIRM, “we will begin recruiting patients the first week we have approval.”

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CIRM Scholar Helen Fong on Stem Cells and Brain Disease

/ Karen Ring / 1 Comment

Helen Fong, CIRM Scholar and Research Scientist at the Gladstone Institutes

Helen Fong, CIRM Scholar and Research Scientist at the Gladstone Institutes

Meet another one of our talented CIRM Scholars, Helen Fong. She is currently a Research Scientist at the Gladstone Institutes and did her graduate work at the University of California, Irvine. Her passions include stem cells, disease modeling, and playing with differentiation protocols – the processes that tell stem cells to mature into specific tissues. As a CIRM Scholar, part of our educational training programs, Helen published four articles where she was listed as the first author. Her most recent one was a stellar study published in Stem Cell Reports using induced pluripotent stem cells (iPSCs) to model and understand a nerve cell-destroying brain disease called frontotemporal dementia.

We interviewed Helen to learn more about her work in stem cell research.

Q: What was your graduate school research on?

HF: I did my graduate work in the lab of Dr. Peter Donovan, who is a prominent germ cell and stem cell scientist, and was newly recruited to UCI when I began my studies. I was his first graduate student from UCI. Dr. Donovan’s research was focused on understanding the regulation of early human development using embryonic stem cells (ESCs) and how to improve human pluripotent stem cell culture. He was also interested in understanding the biological mechanisms that keep stem cells pluripotent (the ability to become all the other cell types in the body) and the genetic factors that are important for maintaining pluripotency. My graduate research was on understanding the basic biology of human ESCs. Specifically, I studied the role of the gene Sox2 in maintaining stem cell pluripotency and self renewal in human ESCs.

Q: What about your postdoctoral research?

HF: After my PhD, I decided to continue to work with stem cells because I knew that the field would continue to grow. There was still so much to be learned about these unique cells. I also genuinely enjoyed working with stem cells and couldn’t imagine not seeing them every day. I realized that I had a solid understanding of the basic biology of ESCs, but I wanted to use stem cells to study human disease. This ability is one of the huge selling points of working with human induced pluripotent stem cells (iPSCs) [which are created by reprogramming adult cells back to a pluripotent state]. The Gladstone Institutes was an excellent place to continue my training and to begin using iPSCs to understand neurological disease. I joined Dr. Yadong Huang’s lab in 2011 and am currently using human iPSCs to study brain degenerative diseases including frontotemporal dementia (FTD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD).

My recent publication in Stem Cell Reports used human iPSCs from a patient with FTD as a model to understand the mechanisms behind this condition. This patient carried a rare genetic mutation in the MAPT gene called TAU-A152T. Several studies have reported a number of patients with this specific mutation that could put them at risk for developing FTD, PSP, and AD. However, it wasn’t clear what this mutation was doing to cause these disorders.

One of the ways you can study neurodegenerative diseases is using stem cells derived from patients harboring the disease causing mutations. We obtained human iPSCs made from the skin cells of a patient with FTD and this TAU mutation. I then used zinc finger nuclease (ZFN) genome editing technology to genetically correct the mutation back to the wild type (normal) sequence to see if removing this mutation in the patient iPSCs would generate healthier neurons (nerve cells) that don’t have symptoms of FTD. I was able to study the disease-causing effects of the TAU mutation by comparing healthy neurons I made from the corrected (normal) iPSC line to diseased neurons made from the TAU mutant iPSC line.

Neurons generated from FTD patient iPSCs. (Image courtesy of Helen Fong)

Neurons generated from FTD patient iPSCs. (Image courtesy of Helen Fong)

The neurons that I differentiated from the iPSCs carrying the TAU mutation showed an increase in TAU protein fragmentation [meaning the protein gets degraded and isn’t present in its normal form], an abnormal characteristic that can be associated with FTD and AD. We didn’t see this phenomenon in the neurons from the corrected (normal) human iPSCs, indicating that removal of this TAU mutation could improve the symptoms of these diseases. These results were exciting because we now had a culprit for what could be causing disease in these patients with this mutation. There is still much to be learned about the mechanisms of this mutation and the iPSCs have been an invaluable resource.

Q: What was your experience like as a CIRM scholar?

HF: CIRM has funded me for almost all of my stem cell training and research. I got my first CIRM training grant as a graduate student at UCI in 2006 and was funded for three years as a postdoc at the Gladstone. So I have CIRM to thank for all of my training.

When I first started out as a CIRM scholar, I believe I was part of one of their earlier pre-doctoral training grant programs. As the program expanded, I got to meet many of the other trainees at CIRM research conferences and interact with prominent stem cell scientists in the area. This was an incredible experience because I was exposed to stem cell research outside of my own institute, and I was able to meet all the big players in the field!

CIRM has also been very generous and provided me a travel allowance to attend any scientific conference of my choice. Over the years, I’ve gone to a lot of conferences nationally and internationally including ISSCR (International Society for Stem Cell Research), Keystone symposia, and the Society for Neuroscience (SfN). I have given scientific talks both at Keystone and SfN, and they proved to be excellent exposure for my work as well as a good place to get feedback. Another one of my favorite perks was the ability to purchase reagents for my own work at my own discretion, which gave me some freedom in dictating which direction I wanted my project to go. If I wanted to study a particular protein and needed a specific antibody to do that, I was able to get it with my CIRM funding.

Q: What’s next for your career?

HF: Currently, I am hoping to wrap up the project I am working on in the lab right now and generate a publication. I plan to continue to work on stem cells in the next step of my career and to work on challenging and cutting-edge projects. I feel fortunate for all the training and resources that I’ve received that got me to where I am today, and I hope to pass on many of my skills and knowledge to budding, young scientists.

Q: What is your favorite thing about being a scientist?

HF: I really enjoy the fact that I have so much control over the fate of my stem cells. They have the ability to turn into almost any cell type, and we’ve developed so many protocols to guide them into the exact cell type we want. They don’t always behave, but I think figuring out the personality of each and every cell line is part of the fun.

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Throwback Thursday: Progress to a Cure for ALS

/ Karen Ring / Leave a comment

Welcome to our new “Throwback Thursday” (TBT) series. CIRM’s Stem Cellar blog has a rich archive of stem cell content that is too valuable to let dust bunnies take over.  So we decided to brush off some of our older, juicy stories and see what advancements in stem cell research science have been made since!

ALS is also called Lou Gehrig's disease, named after the famous American baseball player.

ALS is also called Lou Gehrig’s disease, named after the famous American baseball player.

This week, we’ll discuss an aggressive neurodegenerative disease called Amyotrophic Lateral Sclerosis or ALS. You’re probably more familiar with its other name, Lou Gehrig’s disease. Gehrig was a famous American Major League baseball player who took the New York Yankees to six world championships. He had a gloriously successful career that was sadly cut short by ALS. Post diagnosis, Gehrig’s physical performance quickly deteriorated, and he had to retire from a sport for which he was considered an American hero. He passed away only a year later, at the young age of 37, after he succumbed to complications caused by ALS.

A year ago, we published an interesting blog on this topic. Let’s turn back the clock and take a look at what happened in ALS research in 2014.

TBT: Disease in a Dish – Using Human Stem Cells to Find ALS Treatments

This blog featured the first of our scintillating “Stem Cells in Your face” video series called “Treating ALS with a Disease in a Dish.” Here is an excerpt:

Our latest video Disease in a Dish: That’s a Mouthful takes a lighthearted approach to help clear up any head scratching over this phrase. Although it’s injected with humor, the video focuses on a dreadful disease: amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, it’s a disorder in which nerve cells that control muscle movement die. There are no effective treatments and it’s always fatal, usually within 3 to 5 years after diagnosis.

To explain disease in a dish, the video summarizes a Science Translation Medicine publication of CIRM-funded research reported by the laboratory of Robert Baloh, M.D., Ph.D., director of Cedars-Sinai’s multidisciplinary ALS Program. In the study, skin cells from patients with an inherited form of ALS were used to create nerve cells in a petri dish that exhibit the same genetic defects found in the neurons of ALS patients. With this disease in a dish, the team identified a possible cause of the disease: the cells overproduce molecules causing a toxic buildup that affects neuron function. The researchers devised a way to block the toxic buildup, which may point to a new therapeutic strategy.

New Stem Cell Discoveries in ALS Make Progress to Finding a Cure

So what’s happened in the field of ALS research in the past year? I’m happy to report that a lot has been accomplished to better understand this disease and to develop potential cures! Here are a few highlights that we felt were worth mentioning:

  • The Ice Bucket Challenge launched by the ALS Association is raising awareness and funds for ALS research.

    The Ice Bucket Challenge launched by the ALS Association is raising awareness and funds for ALS research.

    Ice Bucket Challenge. The ALS Association launched the “world’s largest global social media phenomenon” by encouraging brave individuals to dump ice-cold water on their heads to raise awareness and funds for research into treatments and cures for ALS. This August, the ALS Association re-launched the Ice Bucket Challenge campaign in efforts to raise additional funds and to make this an annual event.

  • ALS Gene Mapping. In a story released yesterday, the global biotech company Biogen is partnering with Columbia University Medical Center to map ALS disease genes. An article from Bloomberg Business describes how using Ice Bucket Money to create “a genetic map of the disease may help reveal the secrets of a disorder that’s not well understood, including how much a person’s genes contribute to the likelihood of developing ALS.” Biogen is also launching a clinical trial for a new ALS drug candidate by the end of the year.
  • New Drug target for ALS. Our next door neighbors at the Gladstone Institutes here in San Francisco published an exciting new finding in the journal PNAS in June. In collaboration with scientists at the University of Michigan, they discovered a new therapeutic target for ALS. They found that a protein called hUPF1 was able to protect brain cells from ALS-induced death by preventing the accumulation of toxic proteins in these cells. In a Gladstone press release, senior author Steve Finkbeiner said, “This is the first time we’ve been able to link this natural monitoring system to neurodegenerative disease. Leveraging this system could be a strategic therapeutic target for diseases like ALS and frontotemporal dementia.”
  • Stem cells, ALS, and clinical trials. Clive Svendsen at Cedars-Sinai is using gene therapy and stem cells to develop a cure for ALS. His team is currently working in mice to determine the safety and effectiveness of the treatment, but they hope to move into clinical trials with humans by the end of the year. For more details, check out our blog Genes + Cells: Stem Cells deliver genes as drugs and hope for ALS.

These are only a few of the exciting and promising stories that have come out in the past year. It’s encouraging and comforting to see, however, that progress towards a cure for ALS is definitely moving forward.

Peering inside the brain: how stem cells could help turn skin into therapies for dementia

/ Kevin McCormack / Leave a comment

To truly understand a disease you need to be able to see how it works, how it causes our body to act in ways that it shouldn’t. In cancer, for example, you can take cells from a tumor and observe them under a microscope to see what is going on. But with diseases of the brain it’s much harder. You can’t just open someone’s skull to grab some cells to study. However, now we have new tools that enable us to skip the skull-opening bit, and examine brain cells in people with diseases like dementia, to see what’s going wrong, and maybe even to get some ideas on how to make it right.

AF_neuronTHMito(2)_webThe latest example of this comes from researchers in Belgium who have developed a new strategy for treating patients with an inherited form of dementia. They used the induced pluripotent stem cell (iPSC) method, taking take skin cells from patients with frontotemporal dementia, and turning them into neurons, the kind of brain cell damaged by the disease. They were then able to study those neurons for clues as to what was happening inside the brain.

The study is reported in the journal Stem Cell Reports, and in an accompanying news release the senior author, Catherine Verfaillie, says this approach allows them to study problems in the brain in ways that weren’t possible before.

“iPSC models can now be used to better understand dementia, and in particular frontotemporal dementia, and might lead to the development of drugs that can curtail or slow down the degeneration of cortical neurons.”

The researchers identified problems with a particular signaling pathway in the brain, Wnt, which plays an important role in the development of neurons. In patients with frontotemporal dementia, the neurons weren’t able to mature into cortical neurons, which play a key role in enabling thought, perception and voluntary movement. However, by genetically correcting that problem they were able to restore the ability of the neurons to turn into cortical neurons.

Philip Van Damme, a lead researcher on the project, says this may open up possible ways to treat the problem.

“Our findings suggest that signaling events required for neurodevelopment may also play major roles in neurodegeneration. Targeting such pathways, as for instance the Wnt pathway presented in this study, may result in the creation of novel therapeutic approaches for frontotemporal dementia.”