Stem Cell Research

Transplanted Neural Stem Cells Produce Myelin

Human neural stem cells developed by Stem Cells, Inc. were injected directly into the brains of four young children with an early-onset, fatal form of a condition known as Pelizaeus-Merzbacher disease (PMD). The neural stem cells successfully engrafted into the brains of patients and appear to have produced myelin.

Patients with early-onset PMD cannot walk or talk, often have trouble breathing and undergo progressive neurological deterioration leading to death as a result of an inherited genetic defect that prevents brain cells called oligodendrocytes from making myelin.

The investigators found evidence that the stem cells had successfully engrafted, receiving blood and nutrients from the surrounding tissue and integrating into the brain, a process that David H. Rowitch, MD, PhD, professor of pediatrics and neurological surgery at UCSF, chief of neonatology at UCSF Benioff Children’s Hospital and a Howard Hughes Medical Institute Investigator, likened to “a plant taking root.”

Condensed and adapted from the UCSF announcement.

Neuralstem Reports Positive Pre-Clinical Test Results With Long-Distance Growth and Connectivity of Neural Stem Cells After Severe Spinal Cord Injury

On the news, Neuraltem's market capitalization began the trading day at $54M and ended at approximately $74 million after reaching $105M midday. After close of market, the company released a statement of its intention to carry out a public offering of shares.

In the study, rats with surgically transected spinal cords, which rendered them permanently and completely paraplegic, were transplanted with Neuralstem's spinal cord stem cells (NSI-566).

Neuralstem reports that the animals recovered significant locomotor function, regaining movement in all lower extremity joints, and that the transplanted neural stem cells turned into neurons which grew a "remarkable" number of axons that extended for "very long distances" over 17 spinal segments, making connections both above and below the point of severance. These axons reached up to the cervical region (C4) and down to the lumbar region (L1). They also appeared to make reciprocal synaptic connectivity with the host rat spinal cord neurons in the gray matter for several segments below the injury.

Re-transecting the spinal cord immediately above the graft abolished the functional gain, indicating that the regeneration of host axons into the human stem cell graft was responsible for the functional recovery.

The cells that Neuralstem contributed to the study, NSI-566, are the same cells used in the recently completed Phase 1 clinical trial for the treatment of amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).  Neuralstem has also submitted an application to the FDA for a trial to treat chronic spinal cord injury with these cells.

Adapted from the Neuralstem announcement.

Stem Cell Sector, Neuralstem's (CUR), Short Term Bet On A Molecular Cure For Depression

Neuralstem's technology enables the isolation and large-scale expansion of human neural stem cells from the developing human brain and spinal cord. In addition, the company has developed and patented a series of small molecule compounds -- low molecular weight organic compounds which can efficiently cross the blood/brain barrier -- they are wagering will stimulate the growth of new neurons in the hippocampus and provide a treatment for depression. If they're right, they and their shareholders win big. If they're wrong they'll be in the market for capital and they'll be there with less leverage than they have now.

The company has also developed a Spinal Cord Delivery Platform and Floating Cannula that has been demonstrated to deliver therapeutic agents to the spinal cord safely and effectively, a technology they have just licensed to Salt Lake City-based Q Therapeutics.

Nueralstem's recent venture into the capital markets was small, notable only for the low price of the offering. In mid-April Nueralstem (CUR) sold at $1.07 the day they announced the retirement of their CFO. In the following four months, which included announcements that additional patients had been dosed in their ALS clinical trial, that the first patient had been treated in their depression trial, the beginning of Zack's coverage of the firm with an 'Outperform' rating, and the receipt of a patent on the "Transplantation of Human Neural Cells for Treatment of

Positive Interim Data From Spinal Cord Injury Trial Reported By StemCells, Inc.

StemCells Inc. reported that interim six-month data from the first patient cohort in a Phase I/II clinical trial of its HuCNS-SC product candidate -- purified human neural stem cells -- for chronic spinal cord injury demonstrates a favorable safety profile and shows gains in sensory function in two of the three patients compared to pre-transplant baselines. The third patient remains stable. The trial is being conducted in Zurich, Switzerland at the University Hospital Balgrist, University of Zurich. The trial is scheduled to end at 12 months.

In general stem cell therapeutic candidates have shown good saftey profiles in the phase one clinical trials both within and outside the United States. As phase II trials begin we will learn more about efficacy in various indications and much more will be known about the potential for actual therapies. Some Sector Companies are already hesitating at the door to Phase II awaiting investor or partner money to procede. In this context StemCells Inc. had net cash resources at June 30 of approximately $5 million. While The California Institute for Regenerative Medicine (CIRM) approved an award to StemCells Inc. for up to $20 million under CIRM's Disease Team Therapy Development Award program (RFA 10-05), the award is to fund preclinical development of StemCells' purified human neural stem cells product candidate as a potential treatment for cervical spinal cord injury.

Patients in the study's first cohort all suffered a complete injury to the thoracic (chest-level) spinal cord. In a complete injury, there is no neurological function below the level of injury. All three patients were transplanted four

Blood-Brain Barrier Building Blocks Generated From Human Stem Cells

The blood-brain barrier -- the filter that governs what can and cannot come into contact with the mammalian brain -- is a marvel of nature. It effectively separates circulating blood from the fluid that bathes the brain, and it keeps out bacteria, viruses and other agents that could damage it.

However, the barrier can be disrupted by disease, stroke and multiple sclerosis, for example, and also is a big challenge for medicine, as it can be difficult or impossible to get therapeutic molecules through the barrier to treat neurological disorders.

Now researchers have transformed stem cells into endothelial cells with blood-brain barrier qualities in a laboratory dish in an attempt to get the blood-brain barrier to share its secrets.

“The nice thing about deriving endothelial cells from induced pluripotent stem cells is that you can make disease-specific models of brain tissue that incorporate the blood-brain barrier,” explains Sean Palecek, a UW-Madison professor of chemical and biological engineering. “The cells you create will carry the genetic information of the condition you want to study.”

Dr. Gary Steinberg: Video Presentation Of Stem Cell Therapy For Stroke

Gary Steinberg, Stanford University, is a pioneer in stem cell research for stroke. This is a CIRM presentation that took place August 19 of 2010. Steinberg presents the subject broadly, touching on most of what has taken place and suggesting ideas of where we're headed in the stem cell therapy for stroke arena.

 

Researchers Transform Mouse Skin Cells Into Neurons, Skipping Induced Pluripotent Stem Cell Stage

The future of regenerative medicine continues to depend on the type of stem cell that is proven most effective, most scalable, and most time and cost efficient to produce.  Approaches include embryonic stem cells, adult stem cells, Induced pluripotent stem cells, from both autologous and allogeneic sources.  One of our Sector Companies, International Stem Cell Corp., is attempting to create a stem cell bank based on parthenogenic stem cells derived from unfertilized eggs (oocytes).  Such a bank would have the following advantages:

1. A scalable bank would contain a manageable number of stem cell lines that will be immunological matches for large patient populations of different ethnic origin.


2. Unlike induced pluripotent stem (iPS) cells these would not involve extensive gene manipulation, which to this point in time have largely unknown biological impact.

We point this out in order to ask ourselves what the potential impact on such a stem cell bank might be from new study results obtained by researchers at Stanford University.  Since human iPS cells were first created in late 2007, the emphasis has been on developing these cells in a faster, cheaper way that also provides safe and predictable biological results when used in regenerative therapies.

But what if the iPS phase can be skipped entirely?  Will adult cells converted, for example, directly  into nerve cells be an eventual solution to Parkinson's Disease?  Or will parthenogenic, or some other more basic, more embryonic-like, cell provide the answer.  Perhaps both will be a solution and success in the market, as well as in therapy, will be a function of efficiency from origin to therapeutic use, and resultant lower cost. Perhaps neither will be universally useful in general therapy, but will be more effective for therapies in particular parts of the body.  At this stage no one knows for sure.  What we do know is that knowledge is expanding rapidly as shown in this current Stanford study.

Stanford researchers have succeeded in transforming mouse skin cells in a laboratory dish directly into functional nerve cells with the application of just three genes. The cells make this transition without first becoming a pluripotent type of stem cell.

Geron Recieves FDA Approval To Begin World's First Human Clinical Trial of An Embryonic Stem Cell-Based Therapy

This is Monday after the Friday morning announcement of the first Phase I trial of an embryonic stem cell therapy.  At this writing Geron's market cap ($645M) is now greater than that of Osiris Therapeutics ($619M).  Osiris is in Phase III trials with Prochymal (not for spinal cord repair), a mesenchymal stem cell therapeutic application derived from adult bone marrow stem cells.  Everything points to Osiris obtaining approval to market Prochymal by the end of 2010.  Prochymal will in all probability be the first stem cell therapeutic application approved for market distribution.

Geron's market cap totaled $415 million at close of market on Thursday.  This morning it hit $650 million before ending the day around $645M.  This $230 million or so increase in market cap is the direct result of the FDA acceptance of the idea (based on the largest investigational drug application - 22,000 pages - ever submitted) that embryonic stem cells are safe enough to test in a small number of human beings (8 to 10 people is the test size).

Stem Cells And Spinal Cord Injuries

Researchers have found that manipulating stem cells prior to transplantation may hold the key to overcoming a critical obstacle to using stem cell technology to repair spinal cord injuries.

This particular research focused on a major support cell in the central nervous system called an astrocyte. When nerve fibers are injured in the spinal cord, the severed ends of the nerve fibers fail to regenerate and reconnect with the nervous system circuitry beyond the site of the injury. During early development, astrocytes are highly supportive of nerve fiber growth, and scientists believe that if properly directed, these cells could play a key role in regenerating damaged nerves in the spinal cord.

Computational Biology Shows Greater RNA Interference (RNAi) Role In Stem Cell Differentiation

In hopes of shedding light on the process of cancer initiation, neurodegenerative disorders, diabetes and other diseases, scientists have combined forces to learn how stem cell differentiation is controlled by microRNAs.

If you haven't read our previous posts, you're already asking yourself what RNA Interference (RNAi) is.  It's a term worth getting familiar with if you're interested in the developing arena of stem cell research and its potential for regenerative medicine.

A First: Embryonic Stem Cells Coaxed To Become Nerve Cells

One of the most difficult challenges in stem cell research is figuring out exactly what biological events cause stem cells to differentiate into specific, functioning cells in the body.  For nerve cells this mystery may now be solved. For the first time, researchers have genetically programmed embryonic stem (ES) cells to become nerve cells when transplanted into the brain.

Stroke, Alzheimer’s, Parkinson’s and Huntington’s disease destroy brain cells, causing speech and memory loss and other debilitating consequences. Transplanting neuronal brain cells could restore at least some brain function, just as heart transplants restore blood flow.  But until now there has been no reliable method of coaxing stem cells to become nerve cells.

“We found that we could create new nerve cells from stem cells, transplant them effectively and make a positive difference in the behavior of the mice,” said Stuart A. Lipton, M.D., Ph.D., professor and director of the Del E. Webb Neuroscience, Aging, and Stem Cell Research Center at The Burnham Institute. “These findings could potentially lead to new treatments for stroke and neurodegenerative diseases such as Parkinson’s disease.”

Study Finds Brain Stem Cells Can Be Awakened

 "Everyday experience leads us to suppose that thoughts pass through the mind with a rapidity that defies the laws of physics. It comes as a stunning surprise to discover that almost the exact opposite is true: the brain is slow—very slow— by comparison with the fundamental forces of the physical world," Jean-Pierre Changeux in The Physiology of Truth: Neuroscience and Human Knowledge.

Neurons use electricity to send signals through the body and brain. Early on it was thought that neurons connected directly with other neurons to allow the transmission. In the 1920s this assumption was found not to be true. Instead, there is generally a gap between communicating neurons. The gap is called the synaptic cleft and a chemical synapse carries the converted electrical signal across the synaptic cleft where it is reconverted into an electrical signal in the receptor neuron.  In terms of raw speed, it's a little like putting regularly spaced sand traps on a NASCAR race course. Chances for problems and quirks in this process are numerous.  The last thing it needs is an inability to replace diseased or destroyed neurons.