International Stem Cell Corporation Announces Completion of Cell Bank for Parkinson's Disease Clinical Trial

CARLSBAD, CA--(Marketwired - February 03, 2015

 - International Stem Cell Corporation (OTCQB: ISCO), a California-based biotechnology company developing novel stem cell-based therapies and biomedical products, today announced that the Company has completed manufacturing of the cell bank of clinical-grade human neural stem cells using its patented process for the recently announced phase 1/2a clinical trial in Parkinson's disease. The cell bank contains over 2.6 billion human cells, sufficient to meet the company's foreseeable clinical trial requirements.

"Completing the production of clinical-grade cells using the previously published protocol is one of the final steps before starting our clinical program," said Ruslan Semechkin, Ph.D., ISCO's Chief Scientific Officer. "Because of the complexity involved in manufacturing live human cell products, having our own GMP facility is not only a strategic advantage, but also allows us to control the production costs. We continue to anticipate, subject to regulatory agency approval, beginning the clinical trial in early 2015 and will provide a further update in the near future."
ISCO's master cell bank of human parthenogenetic neural stem cells (ISC-hpNSC) is produced in compliance with current good manufacturing practices (cGMPs) and the chemistry and manufacturing controls (CMC) discussed in the previously reported pre-IND meeting with the FDA. The cells are karyotypically normal hpNSCs and free of measurable contaminants of human or animal origin. The production of hpNSCs from undifferentiated pluripotent human parthenogenetic stem cells in the master cell bank uses qualified reagents and a standardized protocol developed by ISCO. The undifferentiated human stem cells are derived from the parthenogenetic line and were recently cleared by the FDA for use in clinical trials. Each batch of hpNSC is subjected to standardized quality control testing to ensure viability, sterility and appropriate cellular composition before clinical use. The existing master cell bank and current production scale are sufficient to supply our anticipated product needs through pivotal clinical trials. The cell bank was produced at the company's state of the art GMP manufacturing facility located in Oceanside, Calif. 


About human parthenogenetic neural stem cells
ISC-hpNSCs are a novel therapeutic cellular product derived from the Company's proprietary human pluripotent stem cells. Neural stem cells are self-renewing multipotent cells that are precursors for the main cell types of the central nervous system. The ability of ISC-hpNSCs to differentiate into dopaminergic neurons and express brain-protecting neurotrophic factors offers a new opportunity for the treatment of Parkinson's disease. ISCO's preclinical program includes animal studies to assess the safety and tolerability of our novel cell therapy as well as doses ranging efficacy to be used to design the first clinical trial in Parkinson's disease patients.

About International Stem Cell Corporation
International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenetic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial backgrounds, with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell™. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology (www.lifelinecelltech.com), and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available at www.internationalstemcell.com and companyblog.intlstemcell.com.
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Forward-looking Statements
Statements pertaining to anticipated developments, the expected timing and results of clinical studies and regulatory filings, the potential benefits of research programs and products, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.
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Contacts:
International Stem Cell Corporation
Simon Craw, Ph.D.
Executive Vice President
Phone: (760) 940-6383
Email: ir@intlstemcell.com

Media:

Tony Russo, Ph.D.
Phone: (212) 845-4251
Email: tony.russo@russopartnersllc.com

Martina Schwarzkopf, Ph.D.
Phone: (212) 845-4292
Email: martina.schwarzkopf@russopartnersllc.com

http://health.einnews.com/article/247849780/QLqOxp3ZRpj0M9Sk

Protein threshold linked to Parkinson’s Disease

Excess quantities of a specific protein in the brain dramatically increase the chances of so-called “nucleation events” that could eventually result in Parkinson’s Disease, according to a new study.

Finding a cure for Parkinson’s depends on our ability to understand it. For the first time, we have been able to provide a mechanistic description of the initial, molecular events that can ultimately result in the development of the disease

Celine Galvagnion

The circumstances in which a protein closely associated with Parkinson’s Disease begins to malfunction and aggregate in the brain have been pinpointed in a quantitative manner for the first time in a new study.

The research, by a team at the University of Cambridge, identified a critical threshold in the levels of a protein called alpha-synuclein, which normally plays an important role in the smooth flow of chemical signals in the brain.

Once that threshold is exceeded, the researchers found that the chances that alpha-synuclein proteins will aggregate into potentially toxic structures are dramatically enhanced. This process, known as nucleation, is the first, critical step in the chain of events that scientists think leads to the development of Parkinson’s Disease.

The findings represent another important step towards understanding how and why people develop Parkinson’s. According to the charity Parkinson’s UK, one in every 500 people in the UK – an estimated 127,000 in all – currently has the condition, but as yet it remains incurable.

Dr Celine Galvagnion, a Research Associate at St John’s College, University of Cambridge, and the lead author of the study, said: “Finding a cure for Parkinson’s depends on our ability to understand it. For the first time, we have been able to provide a mechanistic description of the initial, molecular events that can ultimately result in the development of the disease.”

The study suggests that the likelihood of an individual developing Parkinson’s is related to a delicate balance between the protein, alpha-synuclein, and the number of synaptic vesicles in their brain. Synaptic vesicles are tiny, bubble-like structures that help to carry neurotransmitters, or chemical signals, between nerve cells. The cell constantly reproduces the vesicles to enable this.

Under normal circumstances, alpha-synuclein plays a pivotal role in the release of these neurotransmitters from one nerve cell to another. It does this by attaching itself to a thin membrane around the synaptic vesicle, known as the lipid bilayer.

When alpha-synuclein binds to lipid vesicles, it folds into a helical shape in order to perform its function. In certain circumstances, however, the proteins on the vesicle surface misfold and stick together. Once this nucleation process has begun, there is then a danger that free protein molecules within the brain cell will come into contact with the misshapen nucleus on the lipid surface. As these combine, they form thread-like chains, called amyloid fibrils, and start to become toxic to other cells. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy-bodies, are the hallmark of Parkinson’s Disease.

Previous research has suggested that overexpression of alpha-synuclein in the brain is somehow associable with the onset of Parkinson’s, and that the interaction of alpha-synuclein with the lipid bilayer could play a role in modulating the development of the disease, but until now it was not clear why this might be the case.

In the new study, the research team simulated the process by which the proteins attach themselves to the vesicles by creating synthetic vesicles in the lab. These were then incubated with different quantities of alpha-synuclein.

The results showed that when the ratio of protein molecules to vesicles exceeds a level of about 100 (a level 10 times higher than that typically found in a human brain), the proteins attaching themselves to the lipid bilayer around a vesicle are too highly concentrated and bunch together on the surface. As a result, the chances of proteins nucleating on the lipid surface are, remarkably, at least a thousand times higher than the chances of two proteins randomly binding together in solution.

“It became clear in our experiment that there are specific conditions in which you can see the aggregation happening, and other conditions in which you don’t,” Galvagnion added. “It turns out that the ratio determines the ability of alpha-synuclein proteins to nucleate. This provides us with a likely explanation of how the initial steps leading to Parkinson’s occur.”

Together, the results provide, for the first time, a mechanistic description of the key role that membrane interactions can play in the initiation of neurodegenerative diseases, including Parkinson’s Disease.

The full report appears in the new issue of Nature Chemical Biology.

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-      See more at: http://www.cam.ac.uk/research/news/protein-threshold-linked-to-parkinsons-disease#sthash.fKf9Ymr9.dpuf

http://www.cam.ac.uk/research/news/protein-threshold-linked-to-parkinsons-disease

Telegraph health advice: Parkinson's disease

Parkinson's disease is a condition in which part of the brain becomes progressively damaged over many years. 

Symptoms

The three main symptoms of Parkinson's disease are: 

- tremor (involuntary shaking of particular parts of the body) 

- slow movement

- stiff and inflexible muscles 

A person with Parkinson's disease can also experience a wide range of other physical and psychological symptoms, including depression, constipation, problems sleeping (insomnia), loss of sense of smell (anosmia) and memory problems. 

Seeking medical advice

See your GP if you are concerned that you may have symptoms of Parkinson's disease. 

Your GP will ask about the problems you are experiencing and may refer you to a specialist for further tests. 

What causes Parkinson's disease?

Parkinson's disease is caused by a loss of nerve cells in part of the brain called the substantia nigra. This leads to a reduction in the amount of a chemical called dopamine in the brain. 

Dopamine plays a vital role in regulating the movement of the body and a reduction in dopamine is responsible for many of the symptoms of Parkinson's disease. 

Exactly what causes the loss of nerve cells is unclear. Most experts think that a combination of genetic and environmental factors is responsible. 

Who is affected

It's thought that around one in 500 people are affected by Parkinson's disease, which means there are an estimated 127,000 people in the UK with the condition. 

Most people with Parkinson's start to develop symptoms when they are over 50, although around one in 20 people with the condition first experience symptoms when they are under 40. 

Men are more likely to get Parkinson's disease than women.

  

How Parkinson's disease is treated

There is currently no cure for Parkinson's disease, although treatments are available to help reduce the main symptoms and maintain your quality of life for as long as possible. 

These include supportive treatments (such as physiotherapy and occupational therapy), medication and, in some cases, surgery. 

You may not need any treatment during the early stages of Parkinson's disease as symptoms are usually mild. However, you may need regular appointments with your specialist so that your condition can be monitored. 

Outlook

As the condition progresses, the symptoms of Parkinson's disease can get worse and it can become increasingly difficult to carry out everyday activities without assistance. 

Some people respond well to treatment and only experience mild to moderate disability, whereas others eventually become severely disabled. 

Parkinson's disease does not directly cause people to die, but the condition can place great strain on the body and can make some people more vulnerable to serious and life-threatening infections. 

However, with advances in treatment, most people with Parkinson's disease now have a normal or near-normal life expectancy.

 http://health.einnews.com/article/247677188/d5UoJuE-0CLXthpb

Tipping point of Parkinson's Disease

discovered by Cambridge University Cambridge University discovered the level
at which a protein in the brain suddenly becomes toxic

Feb.2,2015

Dr Celine Galvagnion, a Research Associate at St John's College, University of Cambridge, and the lead author of the study, said: "Finding a cure for Parkinson's depends on our ability to understand it. For the first time, we have been able to provide a mechanistic description of the initial, molecular events that can ultimately result in the development of the disease.

“This provides us with a likely explanation of how the initial steps leading to Parkinson's occur."

According to the charity Parkinson's UK, one in every 500 people in the UK - an estimated 127,000 in all - currently has the condition, but as yet it remains incurable.

Previous research has suggested that overexpression of alpha-synuclein in the brain is somehow linked to the onset of Parkinson's.

Together, the results provide, for the first time, a mechanistic description of the key role that membrane interactions can play in the initiation of neurodegenerative diseases, including Parkinson's Disease.

The development was welcomed by charities. 

Dr Arthur Roach, Director of Research and Development at Parkinson’s UK, said:

“The formation of deposits of the protein alpha-synuclein in the brain is characteristic of Parkinson’s and some related brain diseases. 

“The precise role this plays in the disease is not completely understood but it is believed to contribute to the damage to brain cells. 

“In the disease process this aggregation takes place inside cells with a highly complex collection of lipid membranes, so any conclusions can only be used as a guide to what might happen in Parkinson’s.”

http://health.einnews.com/article/247677188/d5UoJuE-0CLXthpb

Blue light potential for Parkinson's treatment

Blue light and an internet cable could be used to treat Parkinson's disease with potentially less side effects than current treatments.

A University of Otago study on rats has used light treatment, called optogenetics, to treat isolated cells leaving healthy cells untouched.

About 10,000 New Zealanders suffer from the illness which causes the progressive degeneration of the dopamine-producing cells in the brain and has symptoms such as tremors, rigidity and slow movement.

Traditional treatments include drugs, which can cause nausea, or electrical deep brain stimulation. The latter affects all cells in the region and can lead to strokes during surgery or altered mood.

But a University of Otago study on rats has used a light treatment, called optogenetics, to treat isolated cells leaving other healthy cells untouched.

A neuroscientist from the university's school of medicine, Dr Louise Parr-Brownie, said the technique involved placing light sensitive proteins into cells and then implanting a fibre optic probe, similar to the technology in internet cables, into the brain. That probe is then connected up to a laser that emitted blue light and stimulated the cells effectively correcting neural activity in a Parkinsonian brain.

She said this focused approach was what made the difference.

"With electrical stimulation every single cell that's close to the electrode will respond, whereas with optogenetics we're very selective and what we're hoping for in the long term is that there'll be fewer side effects because we're being so selective with which type of cells we are activating."

Dr Parr-Brownie said cells were stimulated for ten minutes, then rested for ten, then stimulated for a further ten and it had yielded positive results.

Consciously controlled muscle movements known as reaches improved from ten in five minutes to 60 and she said they planned to increase that to 200 reaches in five minute periods by stimulating the brain for longer.

The treatment has yet to be tested on people but Dr Parr-Brownie said she hoped human trials would begin within the next five years eventually leading to the development of a pace-maker type device which could stimulate the brain day and night.

http://www.radionz.co.nz/news/national/265017/blue-light-potential-for-parkinson's-treatment