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Brain Cancer News for November 2004 - Return to menu
Peregrine Pharmaceuticals and New Approaches to Brain Tumor Therapy (NABTT) Consortium Enter Collaboration to Treat Brain Cancer Patients
Study Begins Initial Phase of Cotara(R) Brain Cancer Registration Trial
TUSTIN, Calif., Nov. 9 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) announced today that it has entered into a collaboration with the New Approaches to Brain Tumor Therapy (NABTT) Consortium to initiate the first phase of Peregrine's FDA-approved product registration trial using Cotara(R) to treat patients with recurrent glioblastoma multiforme (GBM), a deadly form of brain cancer. This trial will enroll up to 28 patients to evaluate dosing, safety, radiation exposure and patient survival time.
"Glioblastoma multiforme has proven remarkably resistant to multiple forms of therapy. The use of a locally targeted radioactive antibody is a rational approach to improving outcome in these patients," said Dr. Robert Lustig, clinical associate professor of the Department of Radiation Oncology at the University of Pennsylvania Medical Center. "NABTT has extensive experience testing novel local therapies for glioblastoma and we hope to extend our collaboration with Peregrine to further treatment of this devastating disease."
The American Cancer Society estimates that in the U.S., 18,400 malignant tumors of the brain or spinal cord will be diagnosed during 2004 and approximately 12,690 people will die from these malignant tumors. The average survival time for patients with GBM from time of diagnosis is approximately 12 months.
"We have been working closely with NABTT over the past few months to finalize a protocol that would meet both scientific and regulatory objectives," stated Joseph Shan, director of clinical and regulatory affairs at Peregrine. "This partnership will allow us to begin the initial phase of the previously FDA-approved product registration trial to supplement the safety, efficacy and dosimetry data we have collected in previous trials."
The clinical protocol for the proposed study has been re-submitted by NABTT to the National Cancer Institute (NCI) for final review. The study will be partially funded by NABTT through an NCI grant.
"We are extremely pleased to have an opportunity to work with a prestigious group such as NABTT," said Steven King, Peregrine's president and CEO. "Initiating patient treatment in this clinical study will be an important milestone in the development of Cotara(R)."
About Cotara(R) and Tumor Necrosis Therapy (TNT)
Cotara(R) is the registered trademark for a chimeric TNT antibody attached to Iodine 131, a radioactive agent. Cotara(R) is designed to bind to the dead or dying tissue within the tumor and, once bound, its radioisotope irradiates nearby cells resulting in the death of nearby tumor cells.
Rapidly growing tumors quickly outgrow their blood supply resulting in a region of tumor cells that do not receive adequate oxygen, nutrients and waste removal. The accumulation of dying cells results in the formation of a dead, or necrotic, core present in virtually all solid tumors beyond a very small size. TNT-based products directly target and bind to dead and dying tumor cells found in virtually all solid tumors. By using the necrotic core as a stable anchorage in the heart of a tumor, TNT-based therapeutic agents have the potential to deliver therapeutic agents preferentially targeted to virtually all solid tumors, including brain, lung, colon, breast, liver, prostate and pancreatic cancers.
About NABTT
The primary objective of the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium is to improve the therapeutic outcome for adults with primary brain tumors. This consortium is one of two nationwide that is funded by the National Cancer Institute to conduct Phase I and II clinical evaluations of promising new treatment strategies (surgery, radiation, chemotherapy, and biologic therapies), routes of administration, and clinical trial design in the treatment of primary malignancies of the central nervous system. The NABTT CNS Consortium is specifically designed to combine and focus the experience, resources, and capabilities of nine outstanding medical institutions (Emory University, Cleveland Clinic, Henry Ford Hospital, Johns Hopkins University, Mass General Hospital, Moffitt Cancer Center, NCI Neuro- Oncology Intramural Program, University of Alabama, University of Pennsylvania, Wake Forest University) to bear on primary brain tumors. Additional information about NABTT can be found at http://www.nabtt.org/ .
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals is a biopharmaceutical company primarily engaged in the research, development, manufacture and commercialization of cancer therapeutics and diagnostics through a series of proprietary platform technologies. The company is primarily focused on discovering and developing products that affect blood vessels and blood flow in cancer and other diseases. Peregrine's vascular research programs fall under several different proprietary platforms, including Anti-Phospholipid Therapy (APT), Vascular Targeting Agents (VTAs), Anti-Angiogenesis and Vasopermeation Enhancement Agents (VEAs). The company is working closely with the U.S. Food and Drug Administration (FDA) to initiate its first clinical trial under its APT program using Tarvacin(TM). Tarvacin(TM) is an antibody that binds to the phospholipid, phosphatidylserine, which binds directly to tumor blood vessels to inhibit tumor growth and development.
Peregrine's most clinically advanced therapeutic program is known as Tumor Necrosis Therapy (TNT) and targets dead or dying tumor cells that are common to the majority of different tumor types. The company is developing a radioactive TNT agent that it has trademarked Cotara(R) for the treatment of cancer. The company is working with New Approaches to Brain Tumor Therapy (NABTT) Consortium to initiate the first phase of Peregrine's U.S. Food and Drug Administration (FDA) approved product registration trial using Cotara(R) to treat patients with brain cancer. Peregrine has also completed enrollment in a Phase I Cotara(R) clinical trial for the treatment of colorectal carcinoma at Stanford University Medical Center and is working closely with scientific advisors to design Phase II studies using Cotara(R) for other solid tumor indications. In addition, a TNT-based agent similar to Cotara(R) was developed under a licensing agreement in China and has received marketing approval for the treatment of advanced lung cancer.
The company's wholly owned subsidiary, Avid Bioservices, Inc. (http://www.avidbio.com/ ), develops and manufactures monoclonal antibodies and recombinant proteins to support Phase I through Phase III clinical trials for biotechnology companies, including Peregrine.
Copies of Peregrine press releases, SEC filings, current price quotes and other valuable information for investors may be found at http://www.peregrineinc.com/ .
Safe Harbor Statement: This release may contain certain forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Except for historical information presented herein, matters discussed in this release contain certain forward- looking statements. The inclusion of forward-looking statements should not be regarded as a representation by us, or any other person, that the objectives or plans will be achieved. The words "may," "should," "plans," "believe," "anticipate,"
"estimate," "expect," their opposites and similar expressions are intended to identify forward-looking statements. We caution readers that such statements are not guarantees of future performance or events and are subject to a number of factors that may tend to influence the accuracy of the statements, including, but not limited to, risk factors discussed in Peregrine's report on Form 10-K for the year ended April 30, 2004 and subsequent quarterly reports on Form 10-Q. Peregrine disclaims any obligation and does not undertake to update or revise the forward-looking statements discussed in this press release.
Hawk Associates, Inc. (investors)
Frank Hawkins and Julie Marshall
800.987.8256 or
info@hawkassociates.com
Edelman Financial (media)
Jacqueline Hayot
212.704.4465 or
jacqueline.hayot@edelman.com
Quelle: Peregrine Pharmaceuticals, Inc.
'Not a death sentence': Brain tumor survivors join together
Members of support group for brain tumor survivors and those battling illness say diagnosis can be a life-changing experience.
By Scott Hilyard
COPLEY NEWS SERVICE
Peggy Flannigan wasn't too worried.
So mild were her symptoms -- occasional forgetfulness, suddenly sloppy handwriting -- that when her doctor approached her with results of her MRI, she was caught unprepared.
"Peggy," he began, "you have a brain tumor."
"You could have knocked me over with a feather," Flannigan said at her home in Tremont, Ill. "It took a long time for the information to sink in." Every year, nearly 41,000 Americans hear the words Flannigan's doctor spoke to her two years ago.
Primary malignant tumors -- tumors that originate in the brain, not those that have spread from another part of the body -- are the cause of 13,000 deaths in the United States every year. They are the second most common cause of cancer death for children and the third most common for men and women between the ages of 20 and 39. The common perception is that a diagnosis of a brain tumor is tantamount to certain death. However, that's not the case.
Flannigan and Sally Wecker of Peoria, Ill. -- both members of a support group for brain tumor survivors and those battling the illness -- prove the point. "It's not a death sentence, but it can be a life-changing experience," said Flannigan, who is a nursing professor at Bradley University in Peoria.
In the summer of 2002, Flannigan experienced changes in behavior that were more noticeable to others than to herself. "At certain times I had word search problems. I found I couldn't come up with the word I was looking for in conversation," she said. And the quality of her handwriting began to deteriorate.
"It got practically illegible," she said. "But the symptoms were so vague, it was nothing that was really even definable." A tumor was growing inside her skull, pushing into and contorting the size of her brain and beginning to affect its proper functioning.
A brain tumor can affect the entire range of human thought, behavior and creativity determined solely by its location and size. By the time it started to mess with Flannigan's handwriting and memory, it had grown to the size of a tangerine. Her family urged her to see a doctor. "He said he was 98 percent sure it wasn't malignant but that it was something we needed to take care of quickly," Flannigan said.
The diagnosis came on a Friday. Surgeons removed the tumor the following Tuesday. She has been cancer-free ever since, though doctors say there's a 20 percent chance of a recurring tumor. "I prefer to think of it as an 80 percent chance that I won't have another one," she said.
Wecker's story is similar. She was cleaning a fish tank on New Year's Day 2002 with her granddaughter when she tried to respond to a question. "All that came out was 'I-I-I-I-I.' All of a sudden I couldn't get the words out," Wecker said.
Fearing a stroke, she was taken to the emergency room. Tests showed she had an orange-sized tumor pressing against the speech center of her brain. "The doctor said, 'Sally, it doesn't look too good,'" she said. "I thought I was a goner. I had to step back and take a deep breath." Neurosurgeons removed the tumor, and Wecker, like Flannigan, has since been tumor free.
No one is certain what causes brain tumors to grow. It does not appear to be genetic. Environmental causes such as exposure to certain chemicals, living near power lines and excessive cell phone use have been studied, but nothing has been established.
There are more than 100 types of tumors. The two most common -- meningioma and glioblastoma -- are, respectively, the least fatal and the most fatal. The most dangerous tumors are the ones that grow and integrate into the brain, rather than press up against it. But even meningioma tumors -- the type that Wecker and Flannigan had -- can be fatal, depending on where they are in the brain and how big they get.
"I asked what would have happened if I hadn't come in to be tested," Flannigan said. "And (my doctor) said I could have gone into a coma at some point." Something interesting happened to both women following their medical ordeals. Both got actively involved in a support group for brain tumor victims and survivors, and have attended meetings of the American Brain Tumor Association.
"I know people think you put it behind you and move on," Flannigan said. "Moving on doesn't necessarily mean moving away from it." Said Wecker, "You feel very alone when you first learn you have a brain tumor. We're involved because we show that it's not a death sentence."
Tarvacin(TM) Equivalent Plus Radiation Therapy Reduces Tumor Growth by 98%
Data Presented at Vascular Targeting Agent Conference in Cambridge, Massachusetts
TUSTIN, Calif., Nov. 8 /PRNewswire-FirstCall/ -- Peregrine Pharmaceuticals, Inc. (Nasdaq: PPHM - News) announced today that Philip Thorpe, Ph.D., a member of its scientific advisory board, gave the keynote presentation at the Vascular Targeting Agents conference in Cambridge, Massachusetts. Dr. Thorpe's address highlighted a growing body of pre-clinical evidence supporting the development of Vascular Targeting Agents (VTAs), which are designed to seek and destroy pre-existing blood vessels within cancerous tumors by cutting off the tumor's blood supply.
Also presented was new pre-clinical data generated by Dr. Jin He at UT Southwestern Medical Center at Dallas demonstrating that radiation therapy significantly increases the anti-tumor activity of the Tarvacin(TM) equivalent named 3G4. In animals treated with 3G4 plus external beam radiation, tumor growth was reduced by 98% as compared with 85% for radiation therapy alone or 67% with 3G4 alone.
VTAs represent a therapeutic approach that is distinct from the more widely known angiogenesis inhibitors, which slow tumor growth by stopping new blood vessel formation. In contrast, VTAs seek and destroy pre-existing tumor blood vessels within cancerous tumors by cutting off the tumor's blood supply. Dr. Thorpe holds the Serena S. Simmons Distinguished Chair in Cancer Immunopharmacology at Southwestern Medical Center at Dallas.
"VTAs are progressing through pre-clinical development and into clinical trials," said Dr. Thorpe. "This conference is unique in that it brings together experts in all of the various approaches -- we can discuss the research in person, learn from each other and take new ideas coming out of that mix back to the lab and, ultimately, to the clinic."
The inaugural conference, Vascular Targeting Agents: Therapeutic & Diagnostic Development, is taking place at the Hyatt Regency in Cambridge, MA on November 8 and 9, 2004. The conference is being sponsored by the Strategic Research Institute and will include presentations on the most promising candidates in preclinical and clinical development.
About Peregrine Pharmaceuticals, Inc.
Peregrine Pharmaceuticals is a biopharmaceutical company primarily engaged in the research, development, manufacture and commercialization of cancer therapeutics and diagnostics through a series of proprietary platform technologies. The company is primarily focused on discovering and developing products that affect blood vessels and blood flow in cancer and other diseases. Peregrine's vascular research programs fall under several different proprietary platforms, including Anti-Phospholipid Therapy (APT), Vascular Targeting Agents (VTAs), Anti-Angiogenesis and Vasopermeation Enhancement Agents (VEAs). The company is working closely with the U.S. Food and Drug Administration (FDA) to initiate its first clinical trial under its APT program using Tarvacin(TM). Tarvacin(TM) is an antibody that binds to the phospholipid, phosphatidylserine, which binds directly to tumor blood vessels to inhibit tumor growth and development.
Peregrine's most clinically advanced therapeutic program is known as Tumor Necrosis Therapy (TNT) and targets dead or dying tumor cells that are common to the majority of different tumor types. The company is developing a radio- labeled TNT agent that it has trademarked Cotara® for the treatment of cancer. Peregrine has completed enrollment in a Phase I Cotara® clinical trial for the treatment of colorectal carcinoma at Stanford University Medical Center and has received approval from the U.S. Food and Drug Administration ("FDA") to initiate a product registration clinical trial using Cotara® to treat brain cancer. In addition, a TNT-based agent similar to Cotara® was developed under a licensing agreement in China and has received marketing approval for the treatment of advanced lung cancer.
The company's wholly owned subsidiary, Avid Bioservices, Inc. (http://www.avidbio.com ), develops and manufactures monoclonal antibodies and recombinant proteins to support Phase I through Phase III clinical trials for biotechnology companies, including Peregrine.
Copies of Peregrine press releases, SEC filings, current price quotes and other valuable information for investors may be found at http://www.peregrineinc.com .
Safe Harbor Statement: This release may contain certain forward-looking statements that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Except for historical information presented herein, matters discussed in this release contain certain forward- looking statements. The inclusion of forward-looking statements should not be regarded as a representation by us, or any other person, that the objectives or plans will be achieved. The words "may," "should," "plans," "believe," "anticipate," "estimate," "expect," their opposites and similar expressions are intended to identify forward-looking statements. We caution readers that such statements are not guarantees of future performance or events and are subject to a number of factors that may tend to influence the accuracy of the statements, including but not limited to, risk factors discussed in Peregrine's report on Form 10-K for the year ended April 30, 2004 and subsequent quarterly reports on Form 10-Q. Peregrine disclaims any obligation and does not undertake to update or revise the forward-looking statements discussed in this press release.
Peregrine Investor Relations
Frank Hawkins and Julie Marshall
Hawk Associates, Inc. (investor inquiries)
(800) 987-8256 or info@hawkassociates.com
Edelman Financial (media inquiries)
(212) 704-4465 or
jacqueline.hayot@edelman.com
Schering-Plough Files TEMODAL [temozolomide] EU Marketing Application with EMEA for Newly Diagnosed Glioblastoma Multiforme [Brain Tumors]
BRUSSELS, Belgium, Nov. 3, 2004 /PRNewswire/ -- Schering-Plough Europe today reported that it has filed an application with the European Medicines Agency [EMEA] seeking centralized Marketing Authorization in the European Union [EU] for the use of TEMODAL [temozolomide] Capsules for the treatment of patients with newly diagnosed glioblastoma multiforme concomitantly with radiotherapy and then as adjuvant treatment. Glioblastoma multiforme is a form of brain tumor.
The application provides clinical support for the potential use of TEMODAL in this first-line indication based on efficacy and safety data from a recently completed Phase III study conducted by the EORTC[1] in patients with newly diagnosed glioblastoma multiforme.
TEMODAL is currently approved and marketed in the European Union [EU] for the treatment of patients with malignant glioma, such as glioblastoma multiforme or anaplastic astrocytoma, showing recurrence or progression after standard therapy.
Schering-Plough also reported that the U.S. Food and Drug Administration [FDA] has granted six-month priority review status to a similar application filed in the United States.
Temozolomide is an oral cytotoxic alkylating agent. Cytotoxic agents are designed to prevent the replication of cells that divide rapidly, including those in tumors.
The development of temozolomide for expanded indications is consistent with Schering-Plough's strategy to broaden its oncology portfolio and is in line with its plans to build strength in its global franchises through both internal research and external collaborations and licensing opportunities.
Schering-Plough Europe, based in Brussels, Belgium, is part of Schering-Plough Corporation [NYSE: SGP] of Kenilworth, N.J., USA.
Schering-Plough is a global science-based health care company with leading prescription, consumer and animal health products. Through internal research and collaborations with partners, Schering-Plough discovers, develops, manufactures and markets advanced drug therapies to meet important medical needs. Schering-Plough's vision is to earn the trust of the physicians, patients and customers served by its more than 30,000 people around the world. The company is based in Kenilworth, N.J., USA, and its Web site is http://www.schering-plough.com .
Reference:
[1] Concomitant and adjuvant temozolomide [TMZ] and radiotherapy [RT] for newly diagnosed glioblastoma multiforme [GBM]. Conclusive results of a randomized phase III trial by the EORTC Brain & RT Groups and NCIC Clinical Trials Group. R. Stupp, NCIC1, M. Weller, M van den Bent, NCIC2, M. Taphoorn, NCIC3, EORTC Vienna/Regensburg or Padova, D. Lacombs, R.O. Mirimanoff for the European Organization for Research and Treatment of Cancer Brain Tumor & Radiotherapy Groups and National Cancer Institute Canada; Lausanne, Switzerland; Tubingen, Germany, Toronto, ON, Canada; Rotterdam, The Netherlands; Brussels Belgium; London, ON, Canada.
Web site: http://www.schering-plough.com Schering-Plough Corporation
CONTACT:
Media, Robert J. Consalvo, +1-908-298-7409, or Investors, Alex Kelly, +1-908-298-7450, or Janet M. Barth, +1-908-298-7417, all of Schering-Plough
PROMISE OF STEM CELLS AMPLIFIED; NEW EVIDENCE SHOWS CELLS MAY HELP TREAT MANY DISORDERS INCLUDING PARALYSIS AND BRAIN CANCER
Society for Neuroscience | News Releases
Continuing to counter the dogma that once brain cells give out, they're gone forever, new evidence shows that newly created neurons may provide hope for treating a wide variety of disorders.
Embryonic stem cells have been shown to restore movement after paralysis. And with genetic engineering, stem cells can act as sophisticated protein delivery systems. Scientists have used them to deliver GDNF, a factor to aid in the survival of neurons targeted by Parkinson's and Huntington's diseases. Another team has used them to seek and destroy brain tumor cells. And a Norwegian group has proved that even in adults, neural stem cells have the power to become functioning neurons.
Scientists at the University of California , Irvine , have reversed spinal cord damage in paralyzed adult rats, allowing them to walk again. The researchers, led by Hans Keirstead, PhD, used human embryonic stem cells, which have the potential to become any cell type in the entire body—and turned them into oligodendrocytes—a type of cell in the brain. Oligodendrocytes form the fatty substance myelin that insulates the long wirelike extensions of nerve cells, called axons. Oligodendrocytes wrap themselves around these axons, allowing electrical signals to be rapidly transmitted to other cells in the brain and body.
Spinal cord injury results in a cut through the axons, breaking the information circuit and resulting in paralysis. Even if the neurons are able to regrow new axons, they require oligodendrocytes to form new myelin. “By transplanting new oligodendrocytes, we repaired the lost insulation,” Keirstead says.
The researchers manipulated human embryonic stem cells to become oligodendrocyte progenitor cells (OPCs), an intermediate step before becoming oligodendrocytes. Once implanted to the nervous system of rats, the cells completed their maturation.
When the OPCs were transplanted into rats just seven days after a spinal cord injury, the rats regained the ability to walk nine weeks later. Rats that had to wait until ten weeks after injury, however, did not improve with the transplant. Keirstead says that scar-forming cells may block the re-insulation of axons by the oligodendrocytes. “Older, scarred spinal cord injuries pose another hurdle that we have yet to conquer,” he says. “Future studies may find a way around this barrier.”
The broader accomplishment of this work, says Keirstead, is the generation of a highly pure population of oligodendrocytes from human embryonic stem cells. Previous efforts to collect oligodendrocytes from human fetuses resulted in samples contaminated with other cell types and oligodendrocytes at different stages of development. This pure population will allow researchers to explore the value of using oligodendrocytes in other applications.
In other work, scientists at the University of Wisconsin at Madison have rescued the cells that are attacked by Parkinson's disease and Huntington's disease. Both diseases are movement disorders that specifically kill off neurons that use the neurotransmitter dopamine. “Replacement of dopamine neurons using embryonic stem cells has long been the holy grail,” says Clive N. Svendsen, PhD. “But stem cell transplantation can introduce serious problems, including tumors and dyskinesia, or impaired, sporadic muscle movements.”
So instead of replacing the dopamine cells, she and her colleagues found a way to provide support to neurons under attack. Dopamine neurons require glial-derived neurotrophic factor (GDNF) to survive. So even if stem cells could be successfully introduced to an adult brain, chances are they would require GDNF. Yet in an earlier study, Berhstock's group showed that GDNF alone could restore function to the neurons affected by Parkinson's.
In this earlier study, the researchers delivered GDNF to the brains of patients using a pump and a small catheter implanted in the putamen, a brain area severely stricken by Parkinson's disease. But because the delivery system was so localized, the GDNF did not travel very far. Nevertheless, the patients' symptoms and dopamine neurons improved.
“We thought real cells might better deliver GDNF to the brain,” Svendsen says. The group considered using embryonic stem cells, but realized they might lead to tumors and dyskinesia, so they tried neural stem cells. These cells don't have quite the enormous potential of embryonic stem cells, but they can become astrocytes, a type of glial cell found in the brain. Best of all, they do not induce tumors.
“We wanted to use genetically modified stem cells as organic GDNF ‘mini-pumps,'” says Svendsen. In order to get the astrocytes to produce and deliver GDNF, they gave them a gene for the growth factor and another gene that acts as an “on/off switch” for GDNF production. The researchers were able to control the release of GDNF with the antibiotic doxycycline. They lowered GDNF production simply by administering the drug to the animals, and then resumed GDNF production by withdrawing it.
They then transplanted the genetically modified astrocytes into the brains of rats that served as animal models of either Parkinson's disease or Huntington's disease. The GDNF produced by these astrocytes caused the dopamine neurons to sprout new fibers and to transport the GDNF back to the neuron cell bodies, signs of improved neuronal health and function. “The study provides evidence that this delivery method might be used as a clinical tool for Parkinson's and Huntington's diseases,” says Svendsen.
Another group of scientists has used the remarkable ability of human neural stem cells to home in on harmful brain tumors. Evan Snyder, MD, PhD, of the Burnham Institute in San Diego, and his colleagues at Yonsei University in South Korea implanted neural stem cells to adult mice and watched as they attacked the brain tumors.
Cancerous tumors move quickly throughout the brain. “Brain tumors are entirely untreatable because they are so migratory,” says Snyder. “They are inevitably lethal because they can evade even the most extensive surgical excision and therapies. Neural stem cells are uniquely poised to treat tumors because the cells are attracted to areas of abnormality.”
The researchers used genetic engineering to turn the cells into delivery vehicles for therapeutic agents. They inserted the gene for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). This substance, secreted by the implanted stem cells, is like kryptonite to the hazardous tumor cells.
The scientists studied the most lethal type of brain cancer: intracranial glioblastomas. Adult mice with the tumors received transplants of the stem cells that could deliver TRAIL. The stem cells traveled throughout the main tumor site and even to the cancer's satellite locations, called metastases. The stem cells attacked the cancer and reduced tumor size dramatically.
“Treating brain tumors is perhaps the most promising use of stem cells,” Synder says. “It's truly the ‘low-hanging fruit' in the field.”
In other research, scientists at Oslo 's University Hospital have now shown that even adults harbor stem cells that can become real neurons. Throughout our lives, neural stem cells are born in the ventricular zone, the areas inside hollowed-out spaces in the brain that contain cerebrospinal fluid. Several groups of researchers have watched these cells mature into what look like neurons. But the true test of a neuron's function—electrical conductivity—had not yet been seen.
Iver Langmoen, MD, and his colleagues harvested the adult neural stem cells from the ventricular zone of patients undergoing brain surgery. In the laboratory, the stem cells formed aggregates called neurospheres, which must be dissociated before subsequent divisions can occur. After several generations, the researchers treated the cells with a mix of nutrients to help them differentiate into neurons.
They used a tiny electrode designed to measure the electrical activity of individual neurons. This technique, called patch-clamp electrophysiology, revealed that the cells indeed fired action potentials, a neuron's electrical signature. The cells also release glutamate, one of the brain's most important neurotransmitters. In addition, the neurons expressed glutamate receptors, indicating that they could sense glutamatergic messages in addition to sending them.
Final evidence that the cells were able to communicate as neurons came from experiments in which the researchers recorded electrical activity from pairs of neighboring neuronlike cells simultaneously. This cemented the notion that the cells used a classical neuronal mechanism of transmission.
“Stem cells from the adult human brain can develop into functional neurons and establish networks,” says Langmoen. The researchers hope to explore the possibility of autotransplantation, in which neural stem cells gathered from the brain of a patient could be multiplied in the lab and then returned to that person's brain. “Such a scenario would avoid the ethical and immunological complications associated with embryonic stem cell therapy,” Langmoen says.
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