Stem Cell Clinic

A Breakthrough in Stem Cell Treatment? – Equities.com

By Stem Cell Treatment

Asterias Biotherapeutics (AST) continues to generate excitement and buzz around its stem cell treatment for catastrophic spinal cord injury (SCI). I wrote about this historic event back in September. Thats when the company first released results about this transformative medical breakthrough.

Asterias has now released follow-up data. This was gathered at six and nine months after six quadriplegics received treatment. All six continue to show improvement in motor function and sensation. This is truly wonderful news for those with SCI.

There are also broader medical implications and these should be of great interest to investors.

The difference between this stem cell therapy and traditional drug therapies is huge. Drug therapies have specific and mechanistic impacts. But stem cells derived from embryonic cells work a different way. They draw on the massive DNA databanks in their nuclei. They then use these genetic programs to interact with their surroundings and repair damaged structures.

The Asterias oligodendrocyte progenitor cells were derived from a single unused embryo (from an IVF procedure in the late 1990s). Such embryos are often discarded. But this one was donated to create an unlimited number of therapeutic cells. Both the Bush and Obama Administrations approved the cell line.

When injected into the site of a spinal cord injury, these cells create healthy new spinal cord structures. They restore myelin sheaths (which are like an insulating material on nerves) and repair the lesions caused by injury. They send chemical signals that stimulate the growth of nerve cells. They also generate blood vessels that deliver oxygen and nutrients (and clear out toxic substances).

In works of science fiction, you may have read about nanobots. These are theoretical nanomachines that can fix profound biological damage. But the truth is that we all have this type of device in our bodies at the embryonic stage of development. Each uses the complex repair systems that can be found in the human genome.

These are the cells (AST-OPC1) that were given to patients in the SCI trial. The result is that patients who could not breathe on their own can now perform complex physical tasks. We have seen them lift weights, text, and type 35 words a minute and they continue to improve.

Most people assume this therapy must be the most modern of biotechnologies. In truth, its quite old in modern scientific terms. Dr. Michael West oversaw the creation of this therapy over two decades ago as Gerons chief science officer.

When that company stumbled, he brought the clinical trial and Gerons IP into BioTime (*see disclosure below) as Asterias Biotherapeutics. When I spoke to Asterias CEO Steve Cartt, his excitement was palpable. Heres why.

Each year, about 17,000 people experience the kind of spinal cord injuries targeted by the current trial. AST-OPC1 would be the only approved treatment for this condition.

Cartt is now considering plans to extend clinical trials to those who have suffered less serious spinal cord injuries. This means the patient population for AST-OPC1 cells would expand a great deal.

These cells might also be used to treat other neurological diseases. Multiple sclerosis, for example, also involves the deterioration of the myelin nerve sheath. But this is just the tip of iceberg for pluripotent stem cell therapies. Many of our worst diseases can be addressed by these biological nanobots.

If spinal cords can be repaired, so can the connective tissue deterioration that leads to arthritis and joint failures. Im convinced we will see simple injections of stem cells to repair hip, knee, and other joints in the future.

BioTime has also done extensive research into stem cell therapies for heart muscle and cardiovascular repair. In fact, Dr. West has converted some of my cells to embryonic status. He then engineered them to become my heart muscle cells. There have been animal studies as well. The results indicate that these types of cells will repair the damage done by heart attacks.

Next up, though, is blindness. A BioTime subsidiary in Israel, Cell Cure Neurosciences, is in a phase 1/2a trial to treat dry age-related macular degeneration (dry-AMD). Israeli government grants have helped fund this project.

Based on animal trials, it seems that the companys retinal pigment epithelial cells will be successful in treating the leading cause of adult blindness. Dry-AMD is an attractive target because there is no effective treatment. From what Ive learned, I think that these cells will treat the wet form of macular degeneration and other causes of blindness as well.

This is the real importance of the Asterias SCI trial. Right now, were seeing the proof of concept for a biotechnology that will disrupt the entire healthcare market. I've written about this extensively in Tech Digest (subscribe here for free).

This change will happen sooner than you think. Japan has already revised its Pharmaceutical Affairs Act to speed up the approval of stem cell therapies. And on the home front, several of President Trump's candidates for FDA chief have endorsed similar reforms.

(*Disclosure: The editors or principals of Mauldin Economics have a position in BioTime (BTX) which has significant ownership of Asterias stock. They have no plans to sell their position at this time. There is an ethics policy in place that specifies subscribers must receive advance notice should the editors or principals intend to sell.)

This weekly newsletter by biotech expert Patrick Cox highlights research that is much more advanced than most people know, and the profit potential for investors is vast. Read about the latest breakthroughsfrom new, non-invasive cancer treatments to age-reversing nutraceuticals and vaccines that kill any virusas well as the innovative companies that work on them. Get Tech Digest free in your inbox every Monday.

DISCLOSURE: The views and opinions expressed in this article are those of the authors, and do not represent the views of equities.com. Readers should not consider statements made by the author as formal recommendations and should consult their financial advisor before making any investment decisions. To read our full disclosure, please go to: http://www.equities.com/disclaimer

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A Breakthrough in Stem Cell Treatment? - Equities.com

Orthopedic Stem Cell Research and Related Publications

By Stell Cell Research

Safety and Complications Reporting Update on the Re-implantation of Culture-Expanded MesenchymalStemCells using Autologous Platelet Lysate Technique.

Centeno CJ,Schultz JR,Cheever M,Freeman M,Faulkner S,Robinson B,Hanson R.CurrStemCell Res Ther. 2011 Oct 17.

The Centeno-Schultz Clinic, Broomfield, Colorado, USA.

Mesenchymalstemcells (MSCs) hold great promise as therapeutic agents in regenerative medicine. Numerous animal studies have documented the multipotency of MSCs, showing their capabilities for differentiating into orthopedic tissues such as muscle, bone, cartilage, and tendon. However, the safety of culture expanded MSCs for human use has only just begun to be reported. Methods: Between 2006 and 2010, two groups of patients were treated for various orthopedic conditions with culture-expanded, autologous, bone marrow-derived MSCs (group 1: n=50; group 2: n=290-one patient in both groups). Cells were cultured in monolayer culture flasks using an autologous platelet lysate technique and re-injected into peripheral joints or into intervertebral discs with use of c-arm fluoroscopy. While both groups had prospective surveillance for complications, Group 1 additionally underwent 3.0T MRI tracking of the re-implant sites. Results: The mean age of patients treated was 53 +/- 13.85 years; 214 were males and 125 females with mean follow-up time from any procedure being 435 days +/- 261 days. Number of contacts initiated based on time from first procedure was 482 at 3 months, 433 at 6 months, 316 contacts at 12 months, 110 contacts at 24 months, and 22 contacts at 36 months. For Group 1, 50 patients underwent 210 MRI surveillance procedures at 3 months, 6 months, 1 year and 2 years which failed to demonstrate any tumor formation at the re-implant sites. Formal disease surveillance for adverse events based on HHS criteria documented significantly less morbidity than is commonly reported for more invasive surgical procedures, all of which were either self-limited or were remedied with therapeutic measures. Two patients were diagnosed with cancer out of 339 patients treated since study inception; however, this was almost certainly unrelated to the MSC therapy and the neoplasm rate in similar to that seen in the U.S. Caucasian population. Knee outcome data was collected on a subset of patients. Here, >75% improvement was reported in 41.4% while decreasing the improvement threshold to >50% improvement, 63.2% reported an improvement. At an average reporting time of 11.3 months from first procedure average reported relief in the knee sample equaled 53.1% (n=133 reporting). Conclusions: Using both intensive high field MRI tracking and complications surveillance in 339 patients, no neoplastic complications were detected at anystemcell re-implantation site. These findings are consistent with our prior publication and other published reports that also show no evidence of malignant transformation in vivo, following implantation of MSCs for orthopedic use.

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Orthopedic Stem Cell Research and Related Publications

Local stem cell researcher Sally Temple appears on Dr. Oz – Albany Times Union

By Stell Cell Research

From left are Dr. Oz, researcher Sally Temple, patient Patricia Holman, television personality Montel Williams and Dr. Elisabeth Leamy. (Courtesy Sony Pictures Television)

From left are Dr. Oz, researcher Sally Temple, patient Patricia Holman, television personality Montel Williams and Dr. Elisabeth Leamy. (Courtesy Sony Pictures Television)

From left are Dr. Oz, researchers Sally Temple, patient Patricia Holman, Dr. Elisabeth Leamy and television personality Montel Williams. (Courtesy Sony Pictures Television)

From left are Dr. Oz, researchers Sally Temple, patient Patricia Holman, Dr. Elisabeth Leamy and television personality Montel Williams. (Courtesy Sony Pictures Television)

Dr. Oz with Sally Temple, scientific director and co-founder of the Neural Stem Cell Institute. (Courtesy Sony Pictures Television)

Dr. Oz with Sally Temple, scientific director and co-founder of the Neural Stem Cell Institute. (Courtesy Sony Pictures Television)

Local stem cell researcher to appear on Dr. Oz today

Sally Temple has a plea for people considering stem cell therapy to cope with a chronic illness or life-threatening disease: Don't. Not yet.

Temple, co-founder of the Neural Stem Cell Institute in Rensselaer and president of the International Society for Stem Cell Research, has spent her career studying stem cells. Her pre-taped appearance on "The Dr. Oz Show" airs Tuesday, Feb. 14, where she talks about the difference between stem cell research and what she calls the "snake oil" promises of clinics that haven't been approved by the FDA but promise miracle cures for scourges like Alzheimer's and Parkinson's diseases.

Stem cells hold promise for treatment because they are the foundation from which all parts of the human body grow.

There are more than 500 clinics in the country offering unproven therapies, including some in New York state and a lot in Florida. "We know it's going on all around the world," Temple said.

Patients lured by false promises spend a lot of money. Temple said people have taken out second mortgages to cover the costs. But they are also at medical risk, Temple said, because injecting stem cells even the patient's own cells can have unpredictable results.

On TV

The Dr. Oz Show airs at 2 p.m. weekdays on NewsChannel 13 WNYT. Learn more about stem cell research at http://neuralsci.org.

"We're now hearing of people getting dreadful outcomes, tumors and blindness," she said.

It's because, without FDA approval and the long process of testing a new drug, there's no way to know for sure what's in the syringe, Temple said. "It may sound good to take stem cells from your own fat and inject them into your eye, but injecting stem cells that were good at making fat into another part of the body where they were never supposed to be can be disastrous."

Dr. Mehmet Oz said he chose this subject because there are stem cell clinics using the potential of legitimate research to take advantage of patients desperate for help.

"These physicians are violating not only the trust of their patients but also the law and hopefully our show will push the FDA to use its authority to shut them down," Oz said.

Temple said she was impressed by how informed Oz was during the taping for the show in New York City last month, and said it was clear the researchers and producers on the show had done their homework. Montel Williams, a former show host himself, also appeared on the segment. Williams suffers from multiple sclerosis and said he's been approached by clinics who want his celebrity endorsement.

"He was fully aware of lack of research and knew that when you dig for scientific rationale, it's not there," Temple said. "True stem cell therapy is coming, but we have to go through the proper channels and know it's safe."

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Local stem cell researcher Sally Temple appears on Dr. Oz - Albany Times Union

A 60-Year-Old Man With Progressive Anemia While Receiving Checkpoint Blockade Therapy for Relapsed Myelofibrosis – Cancer Network

By Stem Cell Clinic

A 60-year-old man with a history of coronary artery disease and JAK2 V617Fpositive polycythemia vera presented to our bone marrow transplantation clinic with progressive fatigue, splenomegaly, and cytopenias. He had been in good health up until 14 years prior, when he was found to have polycythemia on routine blood work. He was treated with low-dose aspirin and serial phlebotomies for many years without complications. However, he eventually developed worsening thrombocytosis that required treatment with hydroxyurea and anagrelide. A bone marrow biopsy was performed; this demonstrated postpolycythemia vera myelofibrosis, World Health Organization grade 3/3, with 80% cellularity and 2% blasts. Cytogenetics revealed deletion of chromosome 20q. JAK2 V617F mutation testing was performed, and the patient was found to harbor this mutation. Treatment with ruxolitinib was initiated, which within 2 months resulted in resolution of his splenomegaly and improvement in his anemia. However, 1 year later, he developed progressive fatigue, splenomegaly, and worsening anemia, and he was referred for evaluation for hematopoietic stem cell transplantation.

On presentation to our clinic, he complained of significant fatigue and abdominal fullness. Laboratory analysis revealed a white blood cell count of 9,100/L, a hemoglobin level of 9.6 g/dL, and a platelet count of 271,000/L. His spleen measured 22 cm longitudinally on cross-sectional CT imaging. Human leukocyte antigen (HLA) typing was performed on the patient and his siblings, but this did not identify any matched related donors. A search was initiated with the National Marrow Donor Program, but no matched unrelated donors were identified. His two daughters then underwent HLA typing, and both were found to be haploidentical.

He subsequently underwent a haploidentical hematopoietic transplantation with fludarabine/cyclophosphamide/total body irradiation conditioning, followed by posttransplantation cyclophosphamide. His posttransplant course was complicated by polyarticular inflammatory arthritis. Unfortunately, 30 days after transplantation, autologous hematopoietic stem cell recovery was identified through testing for chimerism. Sixty days after his first transplant, he underwent a second haploidentical transplantation utilizing his other daughters stem cells. He first received conditioning with fludarabine and alemtuzumab and again received posttransplantation cyclophosphamide. His posttransplant course was complicated by BK virusassociated cystitis and mild grade 1 cutaneous graft-vs-host disease (GVHD), treated with topical corticosteroids. He continued to have cytopenias, and a bone marrow biopsy (Figure 1) performed 90 days after his second transplant showed persistent myelofibrosis, with deletion 20q on cytogenetics in 3 of 20 metaphase cells. Despite tapering of immunosuppression, he developed progressive loss of donor myeloid chimerism. However, he retained donor T-cell chimerism (> 90%).

Due to progressive disease, he was offered enrollment in a clinical trial utilizing the cytotoxic T-lymphocyteassociated antigen 4 (CTLA-4) checkpoint inhibitor ipilimumab for patients with relapsed hematologic malignancies following allogeneic stem cell transplantation (ClinicalTrials.gov identifier: NCT01822509). On day 395 after his second transplant, he began treatment with ipilimumab at 5 mg/kg. He tolerated the first infusion well, without toxicity. His hemoglobin level was 9.5 g/dL. Twenty-one days later he was given his second dose of ipilimumab; his hemoglobin level was 8.6 g/dL. Fifteen days after his second dose of ipilimumab, his hemoglobin level dropped to 7.7 g/dL and his reticulocyte count increased to 10.1%; his white blood cell and platelet counts remained stable. His lactate dehydrogenase (LDH), total bilirubin, and indirect bilirubin levels rose to 449 U/L, 2.33 mg/dL, and 2.13 mg/dL, respectively. Two days later, his hemoglobin dropped furtherto 7.0 g/dL.

A. Bone marrow biopsy

B. Peripheral blood flow cytometry for CD55 and CD59

C. Direct Coombs test

D. Further donor chimerism studies

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A 60-Year-Old Man With Progressive Anemia While Receiving Checkpoint Blockade Therapy for Relapsed Myelofibrosis - Cancer Network

Vitamins and aminoacids regulate stem cell biology – Phys.Org

By Embryonic Stem Cells

February 16, 2017 Credit: National Research Council of Italy

An International Reserach Team coordinated by Igb-Cnr has discovered a key role of vitamins and amino acids in pluripotent stem cells. The research is published in Stem Cell Reports, and may provide new insights in cancer biology and regenerative medicine

Vitamins and amino acids play a key role in the regulation of epigenetic modifications involved in the progression of diseases such as cancer. The research may have future implications in cancer biology. The study was published in Stem Cell Reports.

"We found that two metabolites, vitamin C and the amino acid L-Proline, are important players in the control of stem cell behaviour. This study shows that pluripotent embryonic stem cells present in the earliest phases of development are pushed toward a more immature 'naive' state by vitamin C, while they are forced to acquire a 'primed' state in the presence of L-Proline. Thus, vitamin C and L-Proline exert opposite effects on embryonic stem cells, and this correlates with their ability to modify DNA (DNA methylation) without altering the sequence, but instead, the regulation of gene expression," explained researcher Gabriella Minchiotti.

Stem cells possess the unique ability to self-renew and differentiate into other cell types, which makes them extremely interesting in medical and biological research. "Embryonic stem cells are the most 'potent' (defined as pluripotent), meaning that they can give rise to all cell types of an organism, such as cardiomyocytes, neurons, bones, etc. Like normal stem cells, cancer stem cells can also self-renew and differentiate, and are believed to be responsible for tumor growth and therapy resistance."

This study provides an important contribution to the understanding of how metabolites regulate pluripotency and shape the epigenome in embryonic stem cells, which have been largely unexplored and recently gained great interest. This knowledge not only enhances our understanding of the biology of normal stem cells but may offer novel insights into cancer stem cell biology, identifying novel potential therapeutic targets.

Explore further: Gene "bookmarking" regulates the fate of stem cells

More information: Stem Cell Reports, dx.doi.org/10.1016/j.stemcr.2016.11.011

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Vitamins and aminoacids regulate stem cell biology - Phys.Org

Seattle company allows blood donors to deep freeze cells for future medical technology – KOMO News

By Uncategorized

SEATTLE - Melissa Wasserman is used to getting stuck. Shes a regular donor of blood but, this trip to Bloodworks Northwest is not intend to save the life of another, but quite possibly her own in the future.

My cells are not getting any younger, so collecting them now is kind of insurance, said Wasserman.

Wasserman is one of the first official customers for Silene Biotech, a pharmaceutical-grade cell preservation service with a relatively simple idea. The intent is a long-term freezing of a customers blood, with the hope that scientists will develop cures to what ails us and the cells could then be thawed and used to heal ourselves.

The older we get, our cells just get damaged and mutilated, said Dr. Alex Jiao, co-founder and CEO of Silene Biotech. We are looking right now to regenerate peoples bodies using stems cells and thats incredible."

Work by scientists at the University of Washington to regenerate portions of the human heart is already showing some success.

Customers of Silene Biotech are banking their blood on the hope the stem cells can be used to regenerate portions of their own faulty organs or joints when the technology become available.

While technology for regenerating people's body's and treating your diseases are still being developed we can preserve their cells today. said Jiao That way they will have a better opportunity to use their own cells for regenerative medicine or personalize therapies."

The process involves a low-volume blood draw. Silene Biotech then processes the blood then isolates the cells and freezes them in their Seattle lab. The blood is then sent to a long-term medical storage facility in Indianapolis, Ind.

The customer retains full ownership of their own cells and can retrieve or destroy them at any time. Customers can also opt in to have the cells used anonymously for scientific purposes.

Jiao said all personal information is kept confidential with Silene Biotech. Theres even a provision in case the company goes out of business.

We prepay a lot of the storage costs, but if we go out of business and [the customers] storage is up, they have the ability to pay for the storage themselves, said Jiao.

Wendy Riedy was one of the companys early beta testers after she saw KOMO Newss initial story on Jiaos idea more than a year ago.

I thought why not, it cant hurt and Im not getting any younger, said Riedy.

In the future, a persons own stem cells could be used to reverse macular degeneration, which runs in Wendys family.

My mother had both knees replaced, said Riedy. If I could not do that using my own stem cells, why would I not want to do that."

The younger the donor, the better shape the stem cells could be and likely free from pre-cancer factors said Jiao. So, Wendy convinced her daughter to bank her blood just in case.

Id like to have that option to utilize my own cells and helping my body heal itself, said Riedys daughter, Chandler Batiste.

The company currently offers two payment options. There is a $50 annual payment plan with a one-time processing fee of $299. Or theres one-time lifetime payment of $999.

Core blood storage via freezing is not a new concept. Its been done for years for diagnostic reasons and large qualities can be frozen for future surgeries.

But, Jiao believes their niche will be smaller, affordable blood storage for future stem cell harvesting.

The ethics come into play when you over-promise and you say theres something today and its not, said Jiao. We definitely dont do that."

Who better to help yourself in the future than yourself.

I do hope that my own self will make me less miserable, said Wasserman.

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Seattle company allows blood donors to deep freeze cells for future medical technology - KOMO News

Salwa center to ‘conduct’ stem cell research: KIPCO – ’70 pc of … – Arab Times Kuwait English Daily

By Stell Cell Research

Al-Ayyar

KUWAIT CITY, Feb 15, (KUNA): Sheikha Salwa Al-Sabah Center for Stem Cell and Umbilical Cord will pave the way forward to develop services and researches in the healthcare sector, said Kuwait Holding Projects Company (KIPCO) Wednesday. Speaking to KUNA, KIPCO Vice Chairman Faisal Hamad Al-Ayyar said that the center will help advance research within the stem cell and umbilical cord domains and will aid in developing a strong partnership between the public and private sectors within health services. Hopefully, this facility will make it easy for the public to access necessary healthcare in Kuwait, said Al-Ayyar who affirmed stem cell and umbilical cord researches will be crucial to the treatment of various Intractable diseases.

Construction According to the company, KIPCO and its group companies will hand over the Sheikha Salwa Sabah Al-Ahmad Stem Cell and Umbilical Cord Center in mid-September 2017, with 70 per cent of the construction of the building now complete. The center, financed through a KD seven million donation made to the Ministry of Health by Masharee Al-Khair Charity Organization on behalf of KIPCO Group, is the Gulf regions firstever center to be dedicated to stem cell research and the storage of umbilical cords.

The Sheikha Salwa Sabah Al- Ahmad Stem Cell and Umbilical Cord Center is being built over a 12,000 m sq plot of land in the Al- Sabah Health Zone, opposite the Maternity Hospital. It has a total built up area of 7,800 m sq and includes a three-floor main building, a utilities building, in addition to external landscaping and parking. The facility includes testing and research laboratories, blood and cord storage banks, research and medical libraries, as well as a lecture theater.

In addition to KD 7 million donation, the Advanced Technology Company, a member of the KIPCO Group, has pledged to provide state-of-the-art equipment for the centers specialized laboratories, cooling systems and stem cell storage facilities. ATCs contribution is valued at KD one million.

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Salwa center to 'conduct' stem cell research: KIPCO - '70 pc of ... - Arab Times Kuwait English Daily

Nanofiber matrix sends stem cells sprawling in all directions – New Atlas

By Embryonic Stem Cells

Human stem cells grown on Kyoto University's "fiber-on-fiber" culturing system(Credit: Kyoto University)

Mighty promising as they are, stem cells certainly aren't easy to come by. Recent scientific advances have however given their production a much-needed boost, with a Nobel-prize winning technology that turns skin cells into embryonic-like stem cells and another that promises salamander-like regenerative abilities being just a couple of examples. The latest breakthrough in the area comes from Japanese researchers who have developed a nanofiber matrix for culturing human stem cells, that they claim improves on current techniques.

The work focuses on human pluripotent stem cells (hPSCs), which have the ability to mature into any type of adult cell, be they those of the eyes, lungs or hair follicles. But that's assuming they can be taken up successfully by the host. Working to improve the odds on this front, scientists have been exploring ways of culturing pluripotent stem cells in a way that mimics the physiological conditions of the human body, allowing them to grow in three dimensions rather than in two dimensions, as they would in a petrie dish.

Among this group is a team from Japan's Kyoto University, which has developed a 3D culturing system it says outperforms the current technologies that can only produce low quantities of low-quality stem cells. The system consists of gelatin nanofibers on a synthetic mesh made from biodegradable polyglycolic acid, resulting in what the researchers describe as a "fiber-on-fiber" (FF) matrix.

The team found that seeding human embryonic stem cells onto this type of matrix saw them adhere well, and enabled an easy exchange of growth factors and supplements. This led to what the researchers describe as robust growth, with more than 95 percent of the cells growing and forming colonies after just four days of culture.

And by designing a special gas-permeable cell culture bag, the team also demonstrated how they could scale up the approach. This is because several of the cell-loaded matrices can be folded up and placed inside the bag, with testing showing that this approach yielded larger again numbers of cells. What's more, the FF matrix could even prove useful in culturing other cell types.

"Our method offers an efficient way to expand hPSCs of high quality within a shorter term," the team writes in its research paper. "Additionally, as nanofiber matrices are advantageous for culturing other adherent cells, including hPSC-derived differentiated cells, FF matrix might be applicable to the large-scale production of differentiated functional cells for various applications."

The research was published in the journal Biomaterials.

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Nanofiber matrix sends stem cells sprawling in all directions - New Atlas

Your brain’s got rhythm: Synthetic brain mimics – Science Daily

By Embryonic Stem Cells

Science Daily
Your brain's got rhythm: Synthetic brain mimics
Science Daily
To model these complex neural circuits, the Pfaff lab prompted embryonic stem cells from mice to grow into clusters of spinal cord neurons, which they named circuitoids. Each circuitoid typically contained 50,000 cells in clumps just large enough to ...

and more »

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Your brain's got rhythm: Synthetic brain mimics - Science Daily

Calcium imbalance within brain cells may trigger Alzheimer’s disease – Medical News Today

By Uncategorized

New research investigates the role of calcium production in Alzheimer's disease. The neurodegenerative process may be caused by a calcium imbalance within the brain cell.

Mitochondria - sometimes referred to as the "powerhouse of the cell" - are small structures that transform energy from food into cell "fuel."

In the mitochondria of a brain cell, calcium ions control how much energy is produced for the brain to function. Previous research has shown that an excessive production of calcium can cause neurons to die, therefore linking a calcium imbalance with the neurodegenerative process involved in Alzheimer's disease.

Until now, however, the exact mechanism that links Alzheimer's-related neurodegeneration and mitochondrial calcium imbalance was unknown. The new research - led by Pooja Jadiya, a postdoctoral fellow at Temple University in Philadelphia, PA - sheds light on this association.

The study was carried out by researchers from the Center for Translational Medicine at Temple University, and the findings were presented at the 61st Meeting of the Biophysical Society in New Orleans, LA.

Jadiya and colleagues studied brain samples from Alzheimer's patients, a mouse model genetically modified to replicate Alzheimer's-like symptoms, and a mutant Alzheimer's-affected cell line.

They examined the mitochondrial alterations in calcium processing, together with reactive oxygen species (ROS) generation, the metabolism of the active amyloid precursor protein, membrane potential, and cell death. They also looked at the activation of the mitochondrial permeability transition pores and oxidative phosphorylation.

In a healthy brain, calcium ions leave a neuron's mitochondria to prevent an excessive buildup. A transporter protein - called the mitochondrial sodium-calcium exchanger - enables this process.

In Alzheimer's-affected tissue, Jadiya and team found that the sodium-calcium exchanger levels were extremely low. In fact, the protein was so low that it was difficult to detect.

The researchers hypothesized that this would cause an overproduction of ROS, which would, in turn, contribute to neurodegeneration.

ROS are molecules that, in high levels, have been shown to damage proteins, lipids, and DNA, thus causing oxidative stress.

The team did find a correlation between the reduced activity of the sodium-calcium exchanger and increased neuronal death.

Additionally, in the mouse model, the scientists found that right before the onset of Alzheimer's, the gene that encodes the exchanger was significantly less active. A decrease in this gene's expression further suggests that the protein exchanger plays a key role in the progression of the disease.

Finally, the scientists also tested this mechanism in an Alzheimer's-affected cell culture model, by artificially boosting the levels of the exchanger.

As hypothesized, the affected cells recovered to a point where they were almost identical to healthy cells. Furthermore, the levels of adenosine triphosphate (ATP) increased, the ROS levels decreased, and fewer neurons died.

ATP is a molecule considered to be the "energy currency of life" by some biologists, as it is required by every activity our body engages in.

John Elrod, a co-author of the study, explains the significance of the findings:

"No one has ever looked at this before using these model systems. It is possible that alterations in mitochondrial calcium exchange may be driving the disease process."

The study may also pave the way for new treatment options, Elrod explains. The team is currently working to reverse the neurodegeneration typical of Alzheimer's disease in mouse models by stimulating the expression of the gene that encodes the sodium-calcium exchanger. This could be achieved with new drugs or gene therapy.

"Our hope is that if we can change either the expression level or the activity of this exchanger, it could be a viable therapy to use early on to perhaps impede Alzheimer's disease development - that is the home run," Elrod says. "We are not even close to that, but that would be the idea."

Learn how scientists can stop and reverse Alzheimer's-related brain damage in mice.

Written by Ana Sandoiu

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Calcium imbalance within brain cells may trigger Alzheimer's disease - Medical News Today

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