Gene Therapy shows Promise in Reversing Congenital Hearing Loss

Washington, July 26 (ANI): A new gene therapy approach can reverse hearing loss caused by a genetic defect in a mouse model of congenital deafness, a new study has revealed.

The findings present a promising therapeutic avenue for potentially treating individuals who are born deaf.

“This is the first time that an inherited, genetic hearing loss has been successfully treated in laboratory mice, and as such represents an important milestone for treating genetic deafness in humans,” senior study author Lawrence Lustig of the University of California, San Francisco, said.

Hearing loss is one of the most common human sensory deficits, and it results from damage to hair cells in the inner ear.

About half of the cases of congenital hearing loss are caused by genetic defects. However, the current treatment options-hearing amplification devices and cochlear implants-do not restore hearing to normal levels.

Correcting the underlying genetic defects has the potential to fully restore hearing, but previous attempts to reverse hearing loss caused by genetic mutations have not been successful.

Addressing this challenge in the new study, Lustig and his team used mice with hereditary deafness caused by a mutation in a gene coding for a protein called vesicular glutamate transporter-3 (VGLUT3).

This protein is crucial for inner hair cells to send signals that enable hearing. Two weeks after the researchers delivered the VGLUT3 gene into the inner ear through an injection, hearing was restored in all of the mice.

This improvement lasted between seven weeks and one and a half years when adult mice were treated, and at least nine months when newborn mice received the treatment.

The therapy did not damage the inner ear, and it even corrected some structural defects in the inner hair cells. Because the specific gene delivery method used is safe and effective in animals, the findings hold promise for future human studies.

“For years, scientists have been hinting at the possibility of gene therapy as a potential cure for deafness,” Lustig said.

“In this study, we now provide a very real and big step towards that goal,” Lustig added.

The study was recently published by Cell Press in the journal Neuron. (ANI)



Published Findings In Human Gene Therapy Methods Journal Demonstrate Cardium’s New Catheter-Based Method Significantly Boosts Gene Delivery To The Heart

July 26, 2012, 9:00 a.m. EDT

SAN DIEGO, July 26, 2012 /PRNewswire via COMTEX/ — Cardium Therapeutics (nyse mkt:CXM) today announced the publication of preclinical findings demonstrating that cardiac ischemia plays an important role in adenovector gene delivery (transfection) in mammalian hearts. The new findings were published in the peer-reviewed journal Human Gene Therapy Methods in an article entitled “Ischemia-Reperfusion Increases Transfection Efficiency of Intracoronary Adenovirus type 5 in Pig Heart in Situ,” which is available online at    .

The published findings demonstrate that Cardium’s innovative technique employing transient cardiac ischemia can be used to dramatically enhance gene delivery and transfection efficiency after one-time intracoronary administration of adenovector in mammalian hearts. Two consecutive but brief periods of coronary artery occlusion combined with co-administration of nitroglycerin increased both adenovector presence (measured by PCR) and transgene expression (assessed by luciferase activity) by over two orders of magnitude (>100 fold) in the heart, as compared to prior intracoronary artery delivery methods.

“The clinical success of DNA-based therapies can be enhanced by employing optimized gene delivery methods,” stated Dr. Gabor M. Rubanyi, Cardium’s Chief Scientific Officer and co-author of the published paper. “In addition, data analysis from the AGENT 1 through 4 clinical studies, involving more than 650 patients in Phase 1/2 through Phase 2/3, showed that patients with more severe forms of coronary artery disease – which is associated with increased ischemia – tended to be more responsive to the one-time administration of Generx than patients with less severe disease. The research results published in Human Gene Therapy Methods extend those findings and demonstrate that Cardium’s new technique for adenovector gene delivery in the heart can be used to dramatically boost adenovector delivery. By enhancing uptake even in patients with less severe forms of disease and ischemia, it would be expected to reduce response variability and allow for the potential treatment of patients with a broader range of associated coronary artery disease. The new treatment protocols for Cardium’s recently-initiated ASPIRE clinical study have been developed to use our knowledge about induced transient ischemia techniques to leverage these research findings and enhance the non-surgical, catheter-based delivery of Generx to the heart,” stated Dr. Rubanyi.

Cardium’s new method of adenovector delivery to the heart takes advantage of the fact that transient ischemia may reduce the permeability barrier of the vascular endothelium and may increase the number of available coxsackie-adenovirus receptors mediating adenovector uptake.  Balloon angioplasty catheters have been used for many years to dilate blocked coronary arteries, sometimes with use of a stent, and these catheters have also been used safely by cardiologists in patients with coronary artery disease to study the effects of brief ischemia.  Cardium’s new technique inflates the balloon in non-narrowed coronary artery areas, just enough to briefly interrupt flow using inflation pressure that is significantly less than that used for performing routine angioplasty procedures.

Cardium’s recently initiated Russian-based ASPIRE Phase 3 registration study of patients with chronic myocardial ischemia and advanced angina pectoris uses transient ischemia techniques during non-surgical percutaneous catheterization with a standard angioplasty catheter together with the intracoronary infusion of nitroglycerin with the Generx® [Ad5FGF-4] product candidate.  The Company’s Generx product candidate is intended to stimulate the growth of collateral blood vessels to effectively bypass coronary artery atherosclerotic blockages without surgical procedures or angioplasty and stents.

The studies published in Human Gene Therapy Methods were conducted at Emory University School of Medicine by Jakob Vinten-Johansen, Ph.D. and colleagues, and were co-sponsored by a Small Business Innovation Research grant from the National Institutes of Health (Cardium Therapeutics) and the Carlyle Fraser Heart Center (Emory).  A presentation titled: “New Perspectives for Angiogenic Gene Therapy to Treat Myocardial Ischemia in Patients with Coronary Disease” was presented at the 2012 American Society of Gene & Cell Therapy Meeting in May 2012 and is available for viewing at    .  At the conference, Cardium also presented a late-breaking poster titled “Transient Ischemia is Necessary for Efficient Adenovector Gene Transfer in the Heart”.  The poster presentation can be viewed at    .

About Generx and the ASPIRE Study

Generx (Ad5FGF-4) is a disease-modifying regenerative medicine biologic that is being developed to offer a one-time, non-surgical option for the treatment of myocardial ischemia in patients with stable angina due to coronary artery disease, who might otherwise require surgical and mechanical interventions, such as coronary artery by-pass surgery or balloon angioplasty and stents.  Similar to surgical/mechanical revascularization approaches, the goal of Cardium’s Generx product candidate is to improve blood flow to the heart muscle – but to do so non-surgically, following a single administration from a standard balloon angioplasty catheter.  The video “Cardium Generx Cardio-Chant” provides an overview Generx and can be viewed at    .

In March 2012, Cardium reported on the ASPIRE Phase 3 registration study to evaluate the therapeutic effects of its lead product candidate Generx in patients with myocardial ischemia due to coronary artery disease. The ASPIRE study, a 100-patient, randomized and controlled multi-center study to be conducted at up to eight leading cardiology centers in the Russian Federation, is designed to further evaluate the safety and effectiveness of Cardium’s Generx DNA-based angiogenic product candidate, which has already been tested in clinical studies involving 650 patients at more than one hundred medical centers in the U.S., Europe and elsewhere.  The efficacy of Generx will be quantitatively assessed using rest and stress SPECT (Single-Photon Emission Computed Tomography) myocardial imaging to sensitively measure improvements in microvascular cardiac perfusion following a one-time, non-surgical, catheter-based administration of Generx.  A recent article, “Cardium’s Heart Disease Gene Therapy Advancing with New Discoveries,” outlining the history of the Generx clinical development program is available at    .

About Cardium

Cardium is a health sciences and regenerative medicine company focused on the acquisition and strategic development of new and innovative bio-medical product opportunities and businesses with the potential to address significant unmet medical needs that have definable pathways to commercialization, partnering and other economic monetizations.  Cardium’s current medical opportunities portfolio, which is focused on health sciences and regenerative medicine, includes the Tissue Repair Company, Cardium Biologics, and the Company’s in-house MedPodium® Health Sciences healthy lifestyle product platform.  The Company’s lead commercial product Excellagen® topical gel for wound care management recently received FDA clearance for marketing and sale in the United States.  Cardium’s lead clinical development product candidate Generx® is a DNA-based angiogenic biologic intended for the treatment of patients with myocardial ischemia due to coronary artery disease.  In addition, consistent with its capital-efficient business model, Cardium continues to actively evaluate new technologies and business opportunities.  In July 2009, Cardium completed the sale of its InnerCool Therapies medical device business to Royal Philips Electronics, the first asset monetization from the Company’s biomedical investment portfolio. News from Cardium is located at    .

Forward-Looking Statements

Except for statements of historical fact, the matters discussed in this press release are forward looking and reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond our control and may cause actual results to differ materially from stated expectations.  For example, there can be no assurance that enhancements in the uptake of adenovectors can be successfully applied to improve the uptake, applicability or therapeutic effects of Generx in human patients; that Generx can be successfully advanced in clinical studies outside of the U.S.; that results or trends observed in one clinical study or procedure will be reproduced in subsequent studies or procedures, or that clinical studies even if successful will lead to product advancement or partnering; that improvements in the formulation or use of Generx will be commercially practicable, or that Generx could be successfully advanced as a therapeutic in developing markets or that the results of studies in such markets could be used to advance or broaden the regulatory or commercialization activities of Generx in the U.S. or other markets; that the ASPIRE clinical study will be successful or will lead to approval of Generx by the Russian Health Authority for marketing and sales in Russia or lead to approvals in other countries of the Commonwealth of Independent States; that additional clinical evidence regarding the safety and effectiveness of Generx that might be obtained in Russia would be useful for optimizing and broadening commercial development pathways in other industrialized countries; that our products or product candidates will not be unfavorably compared to competitive products that may be regarded as safer, more effective, easier to use or less expensive; that FDA or other regulatory clearances or other certifications, or other commercialization efforts will be successful or will effectively enhance our businesses or their market value; that our products or product candidates will prove to be sufficiently safe and effective after introduction into a broader patient population; or that third parties on whom we depend will perform as anticipated.

Actual results may also differ substantially from those described in or contemplated by this press release due to risks and uncertainties that exist in our operations and business environment, including, without limitation, risks and uncertainties that are inherent in the development of complex biologics and in the conduct of human clinical trials, including the timing, costs and outcomes of such trials, our ability to obtain necessary funding, regulatory approvals and expected qualifications, our dependence upon proprietary technology, our history of operating losses and accumulated deficits, our reliance on collaborative relationships and critical personnel, and current and future competition, as well as other risks described from time to time in filings we make with the Securities and Exchange Commission.  We undertake no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof.

Copyright 2012 Cardium Therapeutics, Inc.  All rights reserved.For Terms of Use Privacy Policy, please visit    .

Cardium Therapeutics®, Generx®, Cardionovo(TM), Tissue Repair(TM), Gene Activated Matrix(TM), GAM(TM), Excellagen®, Excellarate(TM), Osteorate(TM), MedPodium®, Appexium®, Linée®, Alena®, Cerex®, D-Sorb(TM), Neo-Energy®, Neo-Carb Bloc®, Neo-Chill(TM), and Nutra-Apps® are trademarks of Cardium Therapeutics, Inc. or Tissue Repair Company.

SOURCE  Cardium Therapeutics

Copyright (C) 2012 PR Newswire. All rights reserved


Microfibers Improve Virus-Based Gene Therapy

Published on August 1, 2012 at 4:30 AM

By Will Soutter

Scientists at the Institute of Bioengineering and Nanotechnology (IBN) have made a significant progress in virus-based gene therapy by successfully allowing the virus to evade the human immune system through the integration of two IBN innovations.

 In a paper published in the Advanced Materials journal, the researchers showed that efficient elimination of cancer cells is possible by encasing therapeutic viruses in microfibers or artificial tissue fibers.

Since 2003, IBN has been exploring the purpose of engineered insect virus for cancer and neurological disorder treatment. In 2006, IBN successfully delivered gene to human embryonic stem cells utilizing a baculoviral vector.

In order to help the virus to evade the body’s own defense mechanism to reach the targeted cells, a research team headed by Dr Shu Wang, IBN Group Leader, selected a novel microfiber fabrication method devised by Dr Andrew C. A. Wan at IBN.

Human tissue fibers are the assembly of proteins and DNA. At present, it is difficult to synthesize artificial tissue fibers from more than one kind of biomolecule. IBN scientists overcame this issue by developing synthetic tissue fibers from two different types of biomolecular materials, namely DNA and peptides utilizing a water-based chemical process. In the process, the researchers introduced two droplets of negatively charged DNA molecules and positively charged peptide molecules in water. When get contacted, the droplets joined together to create a two-component fiber due to their opposite charges.

The same process was used in the addition of baculoviral vectors to the DNA solution for coating the virus with the fibers. Since the structure of the synthetic tissue fiber is analogous to that of human tissue fibers, they disguised the virus by inhibiting the human immune system’s ability to identify the virus, thus preventing its premature deactivation. Experiments on mice with brain cancer demonstrated that microfiber-coated viruses were able to considerably hinder the growth of the tumor and demonstrated prolong survival when compared to treatment involving uncoated viruses.



Gene Therapy to Regenerate Bones

PTI Jul 26, 2012, 10.00AM

LONDON: Scientists claimed to have developed a new method which can mimic real bone tissue and regenerate bones using gene therapy.

Researchers from the Royal College of Surgeons in Ireland (RCSI) have developed a method of repairing bone using synthetic bone graft substitute material, which combined with gene therapy, can mimic real bone tissue and can regenerate bone in patients who have lost large areas of bone from either disease or trauma.

The researchers have developed an innovative scaffold material made from collagen and nano-sized particles of hydroxyapatite which acts as a platform to attract the body’s own cells and repair bone in the damaged area using gene therapy. The cells are tricked into overproducing bone producing proteins known as BMPs, encouraging regrowth of healthy bone tissue, The method can be applied to regenerate tissues in other parts of the body.

“Previously, synthetic bone grafts had proven successful in promoting new bone growth by infusing the scaffold material with bone producing proteins,” professor Fergal O’Brien, Principal Investigator on the project said in a statement.

“These proteins are already clinically approved for bone repair in humans but concerns exist that the high doses of protein required in clinical treatments may have negative side effects such as increasing the risk of cancer,” O’Brien added.

“By stimulating the body to produce the bone-producing protein itself these negative side effects can be avoided and bone tissue growth is promoted efficiently and safely,” O’Brien said.



First Gene Therapy Gets Closer to Market

Thursday, 02 August 2012 Editor

THE first gene therapy to treat a rare illness came closer to market today after the European drugs regulator recommended the medicine for approval across member states.

The therapy, Glybera, is for patients with an unusual genetic disorder that means their bodies fail to make an enzyme that breaks down fat, causing the pancreas to swell. The condition affects one or two people in every million.

Having rejected an application to approve the drug last year, a European Medicines Agency (EMA) committee revised its decision after assessing the treatment in a small group of patients who suffered from severe or multiple attacks of pancreatitis. The recommendation now passes to the European Commission for a formal endorsement.

The approval will see Glybera become the first gene therapy available outside a clinical trial in Europe or the U.S. China approved a gene therapy for cancer in 2004.    “This is a watershed moment. Gene therapy holds incredible promise for people, especially those with rare diseases,” said Tim Coté, former director of the U.S. Food and Drug Administration’s office of orphan products development and now an independent consultant at the Keck Graduate Institute in California. “This is not an isolated example, this is the beginning of something. It paves the way for the approval of other treatments of this kind.”

“There are about 3,000 of these rare genetic diseases out there waiting for a cure and this is the first one to come through. If you ask me, gene therapy is the way we’re going to cure those 3,000 diseases,” Coté added.

Gene therapy works by replacing faulty genes with healthy copies. Though simple to describe, the idea has suffered a series of major setbacks. Many early treatments were ineffective because they failed to deliver healthy genes to the right cells in large enough numbers. And some very early trials were halted after patients died when therapies switched on the wrong genes.


World’s first GM babies born

World’s first GM babies born


The world’s first genetically modified humans have been created, it was revealed last night, 27th June 2012.

The disclosure that 30 healthy babies were born after a series of experiments in the United States provoked another furious debate about ethics.

So far, two of the babies have been tested and have been found to contain genes from three ‘parents’.

Fifteen of the children were born in the past three years as a result of one experimental programme at the Institute for Reproductive Medicine and Science of St Barnabas in New Jersey.

The babies were born to women who had problems conceiving. Extra genes from a female donor were inserted into their eggs before they were fertilised in an attempt to enable them to conceive.

Genetic fingerprint tests on two one-year- old children confirm that they have inherited DNA from three adults –two women and one man.

The fact that the children have inherited the extra genes and incorporated them into their ‘germline’ means that they will, in turn, be able to pass them on to their own offspring.

Altering the human germline – in effect tinkering with the very make-up of our species – is a technique shunned by the vast majority of the world’s scientists.

Geneticists fear that one day this method could be used to create new races of humans with extra, desired characteristics such as strength or high intelligence.

Writing in the journal Human Reproduction, the researchers, led by fertility pioneer Professor Jacques Cohen, say that this ‘is the first case of human germline genetic modification resulting in normal healthy children’.

Some experts severely criticised the experiments. Lord Winston, of the Hammersmith Hospital in West London, told the BBC yesterday: ‘Regarding the treat-ment of the infertile, there is no evidence that this technique is worth doing . . . I am very surprised that it was even carried out at this stage. It would certainly not be allowed in Britain.’

John Smeaton, national director of the Society for the Protection of Unborn Children, said: ‘One has tremendous sympathy for couples who suffer infertility problems. But this seems to be a further illustration of the fact that the whole process of in vitro fertilisation as a means of conceiving babies leads to babies being regarded as objects on a production line.

‘It is a further and very worrying step down the wrong road for humanity.’ Professor Cohen and his colleagues diagnosed that the women were infertile because they had defects in tiny structures in their egg cells, called mitochondria.

They took eggs from donors and, using a fine needle, sucked some of the internal material – containing ‘healthy’ mitochondria – and injected it into eggs from the women wanting to conceive.

Because mitochondria contain genes, the babies resulting from the treatment have inherited DNA from both women. These genes can now be passed down the germline along the maternal line.

A spokesman for the Human Fertilisation and Embryology Authority (HFEA), which regulates ‘assisted reproduction’ technology in Britain, said that it would not license the technique here because it involved altering the germline.

Jacques Cohen is regarded as a brilliant but controversial scientist who has pushed the boundaries of assisted reproduction technologies.

He developed a technique which allows infertile men to have their own children, by injecting sperm DNA straight into the egg in the lab.

Prior to this, only infertile women were able to conceive using IVF. Last year, Professor Cohen said that his expertise would allow him to clone children –a prospect treated with horror by the mainstream scientific community.

‘It would be an afternoon’s work for one of my students,’ he said, adding that he had been approached by ‘at least three’ individuals wishing to create a cloned child, but had turned down their requests.




European regulators back First Gene Therapy Drug

Updated 11:05 AM Jul 22, 2012
        LONDON – European regulators have recommended approval of the Western world’s first gene therapy drug – after rejecting it on three previous occasions – in a significant advance for the novel medical technology.
More than 20 years since the first experiments with the ground-breaking method for fixing faulty genes, scientists and drug companies are still struggling to apply gene therapy in practice.
Friday’s decision by the European Medicines Agency (EMA) is a win for the drug’s maker, the small Dutch biotech company uniQure, and a potential lifeline for patients with the ultra rare genetic disorder lipoprotein lipase deficiency (LPLD).
It comes too late, however, for investors in the previous listed firm Amsterdam Molecular Therapeutics (AMT).
After the earlier rebuffs for its Glybera medicine, AMT was taken private by newly created uniQure in April because it could no longer fund itself in the public markets.
Patients with LPLD are unable to handle fat particles in their blood plasma and are afraid of eating a normal meal because it can lead to acute inflammation of the pancreas.
The disorder – estimated to affect no more than one or two people per million – can cause acute pancreatitis and death.
Winning approval for Glybera proved particularly challenging because the company was only able to test it on 27 patients in clinical trials, due to the rarity of the condition.
That thin evidence base made the European agency reluctant to approve the drug initially.
But the London-based watchdog said it now accepted there was sufficient benefit to justify a green light for the worst-affected patients, on condition that those receiving the one-off therapy continued to be followed.
“This approval unlocks the potential of gene therapy because it is a first at either the EMA or FDA for gene therapy,” uniQure’s chief executive Jorn Aldag said.
“People have been sceptical as to whether the regulators would buy into this concept, which they have now done.”
The idea of treating disease by replacing a defective gene with a working copy gained credence in 1990 with the success of the world’s first gene therapy clinical tests against a rare condition called severe combined immunodeficiency (SCID).
People with SCID – also known as “bubble boy disease” – cannot cope with infections and usually die in childhood.
The field then suffered a major setback when an Arizona teenager died in a gene therapy experiment in 1999 and two French boys with SCID developed leukaemia in 2002.
In China, Shenzhen SiBiono GeneTech won approval for a gene therapy drug for head and neck cancer in 2003 but no products have been approved until now in Europe or the United States.
More recently, some large pharmaceutical companies have also been exploring gene therapy. GlaxoSmithKline, for example, signed a deal in 2010 with Italian researchers to develop a SCID therapy. REUTERS

Gene Therapy Against Nicotine May Someday Help Smokers Quit

Bloomberg News

Gene Therapy Against Nicotine May Someday Help Smokers Quit

By  Elizabeth Lopatto on June 27, 2012

An experimental vaccine against nicotine, delivered using gene therapy, prevents the substance from reaching the brain and may make quitting easier for smokers, a study using mice indicates.

A single dose of vaccine allowed the liver to produce antibodies that stopped most of the nicotine from getting to the brain, according to a study in the journal Science Translational Medicine. The concentration of nicotine in the brains of treated mice was just 15 percent of that in untreated ones.

Of the more than 4,000 chemicals in cigarette smoke, it is nicotine that leads to addiction, the researchers wrote. Keeping the substance away from the brain might stymie nicotine’s addictive power by preventing smokers from enjoying their cigarettes, giving them no incentive to relapse, said Ronald Crystal, one of the study’s researchers.

“This looks really terrific if you’re a mouse, but the caveat is that they aren’t small humans,” said Crystal, the chairman of genetic medicine at Weill Cornell Medical College in New York, in a telephone interview.

The gene therapy delivers the vaccine to the liver using a virus engineered not to be harmful. The gene sequence for the antibodies is inserted into liver cells, which then begin to create antibodies to nicotine.

“The antibody is floating around like Pac-Man in the blood,” Crystal said. “If you give the nicotine and the anti-nicotine gobbles it up, it doesn’t reach the brain.”

Relapse Rate

The idea of vaccines against nicotine has emerged before, in the form of injections used to trigger an immune response. Those methods proved ineffective, according to the researchers. They turned to gene therapy to trigger production of antibodies.

About 20 percent of U.S. adults are smokers, and most relapse shortly after quitting.

“We don’t have very effective therapies,” Crystal said.“The problem is even with the drugs we have now, 70 percent of people go back to smoking within 6 months of trying to quit.”

The virus vector has been previously given to children with a different disease and appears to be safe, he said.

His group plans to continue studying the vaccine in rats and non-human primates, and has talked to pharmaceutical companies about testing, he said. The gene-therapy vaccine method may work in other addictions as well, Crystal said.

The study was funded by the National Institutes of Health, the National Foundation for Cancer Research and the Malcolm Hewitt Wiener Foundation.


Colon Cancer Genomic Mapping May Point Toward Therapies

Bloomberg News

Colon Cancer Genomic Mapping May Point Toward Therapies

By  Ryan Flinn on July 19, 2012

Companies Mentioned

  • BMY

    Bristol-Myers Squibb Co

    • $35.42 USD
    • -0.73
    • -2.06%
  • PFE

    Pfizer Inc

    • $23.7 USD
    • -0.10
    • -0.4%

The largest study of colon cancer tumors to date found new mutations that may cause malignancy in various organs, bolstering research that links the disease more to specific genetic changes than its location in the body.

Researchers sequenced the genomes of 276 tumors, then compared the results with normal cells from the same patients. They found some mutations previously linked to other types of cancer, and new variants that may be targeted by therapies currently in development, said Raju Kucherlapati, a professor at Harvard Medical School and an author of the study.

“It turns out there were a number of novel and very interesting things that tell us about the biology of the tumors, and also point to directions in which therapies can go,”Kucherlapati said in a telephone interview. “Some of the same genes are modified or mutated in many different cancers.”

The research published yesterday by the journal Nature is among recent studies showing how medicines designed to target gene mutations in one cancer may be applied to other malignancies with the same abnormality. These results have spurred drugmakers such as Bristol-Myers Squibb Co. (BMY) (BMY), Pfizer Inc. (PFE) (PFE)and Roche Holding AG (ROG), the world’s biggest maker of cancer medicines, to focus their cancer research on so-called targeted therapies.

About 5 percent of patients in the study had tumors with mutations to the ERBB2 gene, which also has been found in breast and gastric cancers. Herceptin, a $6 billion breast cancer drug from Basel, Switzerland-based Roche, targets that mutation, Kucherlapati said. Herceptin was one of the first cancer medicines aimed at patients whose tumors have this genetic abnormality.

Gene Target

Another potential target for drugmakers is a mutation that caused 22 percent of patients in the study to have high levels or over-expression of the insulin-like growth factor-2 gene. Companies currently working on inhibitors for this gene, include London-based AstraZeneca’s Medimmune unit, which is testing its therapy, MEDI 573, in the first of three trials typically required for regulatory approval.

Other drugmakers are expanding testing of their cancer therapies that focus on specific gene variants. In May, New York-based Pfizer found that Xalkori, its drug that targets adult lung cancer caused by a gene defect, also eradicates the malignancy in some children with rare tumors of the nerves, blood and soft tissue. Bristol-Myers, based in New York, also announced in May it would expand testing of its leukemia drug Sprycel in patients with lung cancer because it appeared to help one patient with a particular mutation.

The data released yesterday are part of a broader project by the National Institutes of Health called the Cancer Genome Atlas, which is analyzing tumors and blood samples from 20 types of cancer.

One of the project’s earlier studies of ovarian cancer patients with a genetic mutation best known for its ties to breast cancer have found they have a higher survival rate than those without the mutation.


Gene Therapy Treatment Extends Lives of Mice with Fatal Disease, MU Study Finds

Gene Therapy Treatment Extends Lives of Mice with Fatal Disease, MU Study Finds

Spinal Muscular Atrophy affects one in 6,000 children; no known cure

July 16, 2012

COLUMBIA, Mo. — A team of University of Missouri researchers has found that introducing a missing gene into the central nervous system could help extend the lives of patients with Spinal Muscular Atrophy (SMA) – the leading genetic cause of infantile death in the world.

SMA is a rare genetic disease that is inherited by one in 6,000 children who often die young because there is no cure. Children who inherit SMA are missing a gene that produces a protein which directs nerves in the spine to give commands to muscles.

The MU team, led by Christian Lorson, professor in the Department of Veterinary Pathobiology and the Department of Molecular Microbiology and Immunology, introduced the missing gene into mice born with SMA through two different methods: intravenously and directly into the mice’s central nervous systems. While both methods were effective in extending the lives of the mice, Lorson found that introducing the missing gene directly into the central nervous system extended the lives of the mice longer.

“Typically, mice born with SMA only live five or six days, but by introducing the missing SMN gene into the mice’s central nervous systems, we were able to extend their lives 10-25 days longer than SMA mice who go untreated,” said Lorson, who works in the MU Bond Life Sciences Center and the College of Veterinary Medicine. “While this system is still not perfect, what our study did show is that the direct administration of the missing gene into the central nervous system provides some degree of rescue and a profound extension of survival.”

There are several different types of SMA that appear in humans, depending on the age that symptoms begin to appear. Lorson believes that introducing the missing gene through the central nervous system is a way to potentially treat humans regardless of what SMA type they have.

“This is a treatment method that is very close to being a reality for human patients,” Lorson said. “Clinical trials of SMA treatment using gene therapy are likely to begin in next 12-18 months, barring any unforeseen problems.”

The study, “Direct central nervous system delivery provides enhanced protection following vector mediated gene replacement in a severe model of Spinal Muscular Atrophy”, was published in Biochemical and Biophysical Research Communications. Co-authors of the study include Jacqueline Glascock and Monir Shababi from MU College of Veterinary Medicine.