BioScience Biz

Hypoxia for treating spinal cord injuries

MADISON - A full recovery from a spinal cord injury?  Don't hold your breath.

Actually, according to Gordon Mitchell, a professor of neurosciences at the University of Wisconsin-Madison School of Veterinary Medicine, holding your breath might be exactly the right thing to do.

Mitchell and team members from the University of Saskatchewan, The Rehabilitation Institute of Chicago, and the Emory School of Medicine are researching innovative spinal cord therapies that earned them the Translational Research Partnership Award this year.  Their research will use short periods of oxygen deprivation to increase spinal cord plasticity, essentially training the spinal cord to compensate for injury.

The award recognizes the team's efforts to bring together people from different schools to translate research into real-world applications.  Years ago, this research was born from the work of the Mitchell laboratory in the UW School of Veterinary Medicine.

The team came together when Mitchell partnered with Gillian Muir, an associate professor of veterinary biomedical sciences at the University of Saskatchewan who did a one-year sabbatical in the Mitchell laboratory, and Randy Trumbower, then a postdoctoral fellow with Dr. Zev Rymer at the Rehabilitation Institute of Chicago.  Trumbower since moved to Emory University, where he is an assistant professor of rehabilitation medicine.  Between the fields of neurology, veterinary science, and physical rehabilitation, these three created the ideal team to tackle spinal cord injuries.  Their success caused Mitchell to pursue the Translational Research Partnership award as a grant opportunity.

"I wanted this partnership to continue," Mitchell says.

Their grant, entitled "Intermittent Hypoxia Elicits Prolonged Restoration of Motor Function in Human Spinal Cord Injuries," offers the team a two-year budget of $750,000 to be coordinated between them as they explore a new therapy for spinal cord injuries.

The treatment, which was inspired by some curious effects seen in sleep apnea patients, involves a breathing mask that provides oxygen, then intervals of oxygen deprivation.  The brief periods without oxygen cause the patient's body to compensate, training their motor neurons to improve breathing.

"But the effects we were having weren't restricted to respiratory motor neurons," says Mitchell.  Preliminary results show an astounding increase in limb muscle function and control, both in rats and humans with partial spinal cord injuries, even after the first treatment.

The team hopes to pair this treatment with physical therapy to get the most out of the "training" of the spinal cord.  "It's nearly impossible to get the spinal cord to regrow," Mitchell says, "but you can train it to do better."

He hopes that this research will reach the public quickly because it is not a drug, and may move through FDA approval quickly if their efforts are successful.

Mitchell predicts that the new treatment could have huge effects on pets with spinal cord injuries from accidents or herniated discs.  "Right now, most of them are simply killed because the prognosis is so bad," says Mitchell. Steven Clark, PhD Associate Professor

The concept is getting attention for the potential human benefits as well.  Because of the interest the Department of Defense is taking in helping soldiers with spinal cord injuries, they are funding the award through the Congressionally Directed Medical Research Programs.

According to the Nov. 4, 2009 issue of USA Today in an article entitled "Spinal injuries up among troops," the rise of roadside bombs has dramatically increased the number of spinal cord injuries as soldiers are battered within the confines of an armored vehicle. Steven Clark, PhD Associate Professor

Mitchell explains that most of these patients have only partial spinal cord injuries, meaning his new treatment has big potential to help them.  With these implications to human and animal health on the horizon, Mitchell's team plans to begin their work this September.

British MD who linked vaccines to autism loses license

Andrew Wakefield published a 1998 article in Lancet that purported to show a link between MMR vaccinations and autism. The paper caused quite a stir in the general public, leading to a sharp drop in MMR vaccination that let to a surge in measles around the world. Wakefield has been a cause célèbre among the anti-vaccine crowd.  Steven S. Clark, PhD

 However, his paper was recently pulled by Lancet after the findings were roundly discredited. Pharmalot, an online news publisher, just reported that Wakefield’s license to practice medicine has been revoked. According to Pharmalot, “The UK’s General Medical Council ruled that Walkefield acted dishonestly, and was misleading and irresponsible while carrying out his research. He “abused his position of trust…brought the medical profession into disrepute” in studies he carried out on children, and found there had been “multiple separate instances of serious professional misconduct”. Steven S. Clark, PhD

Read the full story here.

Healthcare reform dollars for research

You might qualify for up to a 50% tax credit or cash grant if you are a life science company with no more than 250 employees and are undertaking projects to do one of the following:

•    Result in new therapies to treat unmet medical needs or to prevent, detect or treat chronic or acute conditions
•    Reduce long-term healthcare costs in the US
•    Significantly advance the goal of curing cancer

You can find more details here.

How best to deal with neglected diseases?

In 2005, researchers coined the term "neglected tropical diseases" to refer to thirteen diseases primarily occurring in rural, poor areas that have been largely ignored by policymakers and public health officials. These diseases, including sleeping sickness, river blindness, hookworm infection and more, traditionally fall second in attention and funding to "the big three" -- HIV/AIDS, malaria, and tuberculosis. Steven S. Clark

Despite a recent increase in funding for NTDs from private and government sources, there is debate how best to use this money. Would it be more effective to focus on the socio-environmental roots of disease, such as sanitation, clean water, education, etc--or is it best to focus on developing new treatments? The problem with the former is that it is expensive and would take a very long time to accomplish world-wide. The problem with the latter is that drug treatment won't prevent later reworming of treated individuals.

Read more about this in The Scientist or read the debate recently published in PLoS Medicine. Steven S. Clark

Angel-backed companies more likely to succeed, says Harvard study

A new study published by professors at the Harvard Business School shows that angel-backed companies are more likely to succeed and show more growth than those funded by venture firms alone. Researched and written by William Kerr and Josh Lerner, the report found that companies with angel funding see between 30% and 50% higher growth figures in terms of website traffic, are more likely to survive for four years, and are also in a better position to receive further rounds of funding.
Steven Clark

Angel investing itself has seen large growth over the last several months with the creation of various organizations, events, firms and legislation to spur it on. We've discussed the Open Angel Forum series of events, the creation of "Super Angel" firms, the curated Venture Hacks AngelList, as well as current legislation both helping and hurting angel investments. Steven Clark

Read the full article.  Steven Clark

Cashing in on grant opportunities

Maybe you are a small business, or perhaps a health care company, a state agency or even a university researcher and would like to glean some of the largess from the federal recovery act. Or, perhaps you have a timely project that could use funding from a state agency or a private foundation. If so, what would you give for a 55% success rate in securing these highly competitive dollars? Over the last six years, an Ohio and Washington, DC-based company has been providing this grant success rate for a wide range of national clients. grants, federal grants, foundation grants, grant success rate, Gwen Mathews, Strategic Health Care,

The evolution of SHC's grant writing division

Stick with me here as I explain how this company got into the grant writing business. The company, Strategic Health Care, actually has been around for 16 years, specializing in congressional, state and regulatory affairs, public policy analysis, and association management within the health care industry. However, after many of SHC’s clients requested help in finding and securing federal funds, the company established a Federal Grant and Fundraising Division, hiring Gwen Mathews as Senior Vice-President to run the endeavor.

In the beginning, after Mathews was hired away from her own consulting business, there was just Mathews and two part-time grant writers. Six years later, the division boasts three full time employees and a stable of 35 professional contract grant writers and editors as well as some 11 account managers scattered across the US.

While the initial focus of SHC's new grant writing division was to help existing health care clients secure federal grants, the division’s success soon resulted in an expanded role including finding and securing grants from state governments and private sources such as the Avon, Kellogg, Krestge, William Randolph Hearst, Bill and Melinda Gates and Robert Wood Johnson foundations. Furthermore, as word of SHC grant-writing success spread, clients outside the health care industry also began seeking their services. While SHC still emphasizes health care fundraising, the company also has successfully obtained grants for clients from a wide range of federal departments and agencies, including NIH, DoD, DoL, DoE and the USDA. Since this summer, SHC has written and submitted grants for a Houston-based energy company, for a systems biology research project and for the Universities of Tennessee and Cincinnati, among several others.

“Business has mushroomed each year since (setting up the division)…We’re seeing a lot of non-healthcare people taking an interest (in what we have to offer),” explained Mathews. As an example, she said that SHC is in the final stage of negotiations with the state of Delaware to help all of that state’s agencies identify and secure federal grant dollars, most of which would not be healthcare related.

Mathews, who splits her time between SHC’s Columbus and Washington, DC offices, went on to say that SHC has worked on “hundreds” of grant applications over the last six years and that the grant writing division currently has 25 active clients for which about 50 grant applications have recently been submitted and are awaiting funding decisions.

What is the secret for SHC’s success?

“We can help (clients) determine if a project is a good match for the funding opportunity they want to pursue. In terms of return on investment, the average grant is about $500-$600K, with a range of $250K-$3M. So the investment they make (in SHC) enhances the chances of being successful. We bring to the table a group of folks who are very, very skilled in what they do and understand, not just federal grants, but the grant world in general and (who) have a great depth of knowledge (in the grant application process) that the average client doesn’t have.” Mathews said. “In the long run, we really save (our clients) money. We have had many clients come to us who have put in multiple applications that have not been successful and we helped them develop successful applications, so we do save them money.”

Michael Stein, Executive Director of Government Affairs for Bassett Healthcare in New York, used SHC to successfully secure a federal Health Resources and Services Administration grant for a tele-health network system. He pointed out that it was a very complex project involving several partner organizations and had a very short lead time of less than three weeks. Stein searched online for a grant writing service, interviewing several and “…was impressed with the ‘grant game’ at SHC.” SHC put a team of grant writers on the project and made the deadline—normally SHC assigns one account manager and one grant writer to a project, but this illustrates the company’s flexibility in dealing with granting tribulations that many businesses could not tackle.

Stein added that although the grant received the highest score of the many grants that were submitted, it was not funded since they were not in a healthcare shortage area, one of the preferred, but not necessary, requisites in the RFP. Mathews, who was acquainted with the HSRA program officer, called and inquired about the grant’s status, which eventually led to it being funded. In fact, Mathews added that she was close to calling in the government relations team at SHC to see if Bassett’s congressional representatives could influence the agency’s decision. This exemplifies the value of not only having professional grant writers, but also of being familiar with the federal grant system and being able to bring other useful resources to bear in order to address the all-too-frequent exigencies of applying for federal grant funding.

In another example of a satisfied client, Rick Giecek, Chief Development Officer for the University of Tennessee Medical Center said that they have used SHC to apply for 6 grants from the federal and state governments and the Avon foundation, three of which were awarded. Their latest awards totaled almost $1 million for diabetes education and for digital mammography equipment. Giecek opined that “…Strategic does good work, they have a lot of depth and breadth.”

As this article was in preparation, SHC founder and President, Paul Lee, announced in an email that SHC had landed its largest grant for a client--$45 million dollars from the USDA.

That probably would be another satisfied client.

To contact the SHC grants division, email Gwen Mathews at: Gwen.Mathews@shcare.net

For the purpose of fairness, the author discloses that he is a part-time contractor for SHC. grants, federal grants, foundation grants, grant success rate, Gwen Mathews, Strategic Health Care,
© 2009 Steven S. Clark, PhD, some rights reserved.  Articles contained herein, are meant to be distributed freely to interested parties. However, any use, including excerpts from any article, must credit Steven S. Clark and provide a link to the original article published in BioScience Biz.

Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, neither Steven S. Clark, nor other authors, assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.

FDA puts brakes on Geron stem cell trial--again

Last week the New York Times reported that the FDA put a clinical hold on Geron’s pioneering human embryonic stem cell (ESC) trial—before the first patient could be enrolled. In what was to be the world’s first clinical test of ESCs, Geron planned to differentiate the cells into neurons that can be injected into the spinal cords of paralyzed patients. However, the FDA requested more information after reviewing dose escalation data from pre-clinical animal studies.

This is the second time the FDA has delayed the Geron ESC clinical trial. Back in January, the FDA lifted an 8 months hold, allowing Geron to proceed with plans for the experimental injection of ESC-derived nerve cells into the spines of 8-10 paralyzed patients in attempt to repair the neural damage. The FDA was concerned over the safety of the protocol since the presence of any contaminating, undifferentiated ESCs could form tumors called teratomas.

In an announcement released Friday by Geron, the company explained that a recent animal study of the GRNOPC1 ESC therapy revealed the presence of “microscopic cysts in the regenerating injury site.” Fortunately the cysts were only found in the injection site and were non-proliferating. That is significant since it means that the cysts were benign, nevertheless, the FDA wants to look more closely at this development. 

"We have submitted these data to the FDA and are in discussions with the agency to answer its questions and proceed with the clinical trial," said the company in the release.

Researchers uncover possible link between avian flu and Parkinson's disease

Infection with the avian influenza virus might cause a predisposition to Parkinson's disease, according to research published this week in the Proceedings of the National Academy of Sciences. The following article is adapted from a recent report in The Scientist .

Epidemiological studies done in the 1980s showed that survivors of the 1918 Spanish influenza, a flu pandemic that killed more than 50 million people worldwide, had a greater incidence of Parkinson's disease later in life than the general population. Recent studies have suggested that the currently circulating strain of avian influenza has similar pathology to the 1918 flu. Though the subtypes of the viruses are different (Spanish flu shares the H1N1 subtype with the current H1N1 swine flu, whereas avian influenza has an H5N1 subtype), both viruses appear to enter the central nervous system (CNS) and can cause encephalitis, or inflammation of the brain. The study did not look at the ability of the current H1N1, or swine flu strain, to infect the CNS.

Richard Smeyne at St. Jude's Hospital in Memphis, Tennessee, and colleagues infected mice with avian flu and tracked how the infection progressed to the nervous system. "We thought [the virus] would get in [to the CNS] via the blood stream," through the blood brain barrier, said Smeyne. Instead, the virus entered "in a backdoor way," infecting the axon terminals of peripheral neurons first, specifically those of the gut and lung. The virus then traveled from the axon to the neuron cell body, where the researchers think it may be able to infect other neurons to eventually arrive in the brain.

Strikingly, said Smeyne, "this virus was mimicking the pattern of progression of Parkinson's disease." Some scientists think that Parkinson’s disease starts in peripheral neurons and slowly makes its way into the CNS, much like the progression of the flu infection. "It is interesting to me," said Tansey, that the virus "clearly infects the areas that are the most sensitive to chronic inflammation," such as the midbrain, where much of the neuronal death seen in Parkinson's disease occurs.

Smeyne observed a loss of about 17% of dopamine-producing neurons in the infected mice. Parkinson's patients normally lose between 50-80% of their dopamine-producing neurons, and the loss in Smeyne's mice suggests a predisposition to the disease, he said. Although all traces of the virus were cleared from the brain after about 20 days, and there was no evidence of further neuron loss, the virus appeared to have caused a prolonged activation of microglial cells, the immune cells that mediate inflammation in the brain. That effect -- observed 90 days post-infection -- suggests that these cells had become much more sensitive to subsequent neural insults, said Smeyne.

The biggest risk factor for Parkinson's disease, said Smeyne, is age. "We think what is happening with the influenza is that it's shifting the curve" to speed the onset of the disease. Tansey cautioned, however, that the study doesn't indicate the virus necessarily causes Parkinson's, nor does it suggest that more common strains of influenza may predispose people to the disease. It would be interesting to test whether the flu-infected mice would be more likely to develop full-blown Parkinson's disease if they were allowed to age, she said, and to repeat the study in non-human primates.

STUDY SUGGESTS H1N1 VIRUS MORE DANGEROUS THAN SUSPECTED

MADISON, WI - A new, highly detailed study of the H1N1 flu virus shows that the pathogen is more virulent than previously thought.

Writing in a fast-tracked report published recently (July 13, 2009) in the journal Nature, an international team of researchers led by University of Wisconsin-Madison virologist Yoshihiro Kawaoka provides a detailed portrait of the pandemic virus and its pathogenic qualities.

In contrast with run-of-the-mill seasonal flu viruses, the H1N1virus exhibits an ability to infect cells deep in the lungs, where it can cause pneumonia and, in severe cases, death. Seasonal viruses typically infect only cells in the upper respiratory system.

"There is a misunderstanding about this virus," says Kawaoka, a professor of pathobiological sciences at the UW-Madison School of Veterinary Medicine and a leading authority on influenza. "People think this pathogen may be similar to seasonal influenza. This study shows that is not the case. There is clear evidence the virus is different than seasonal influenza."

The ability to infect the lungs, notes Kawaoka, is a quality frighteningly similar to those of other pandemic viruses, notably the 1918 virus, which killed tens of millions of people at the tail end of World War I. There are likely other similarities to the 1918 virus, says Kawaoka, as the study also showed that people born before 1918 harbor antibodies that protect against the new H1N1 virus.

And it is possible, he adds, that the virus could become even more pathogenic as the current pandemic runs its course and the virus evolves to acquire new features. It is now flu season in the world's southern hemisphere, and the virus is expected to return in force to the northern hemisphere during the fall and winter flu season.

To assess the pathogenic nature of the H1N1 virus, Kawaoka and his colleagues infected different groups of mice, ferrets and non-human primates - all widely accepted models for studies of influenza - with the pandemic virus and a seasonal flu virus. They found that the H1N1 virus replicates much more efficiently in the respiratory system than seasonal flu and causes severe lesions in the lungs similar to those caused by other more virulent types of pandemic flu.

"When we conducted the experiments in ferrets and monkeys, the seasonal virus did not replicate in the lungs," Kawaoka explains. "The H1N1 virus replicates significantly better in the lungs."

The new study was conducted with samples of the virus obtained from patients in California, Wisconsin, the Netherlands and Japan.

The new Nature report also assessed the immune response of different groups to the new virus. The most intriguing finding, according to Kawaoka, is that those people exposed to the 1918 virus, all of whom are now in advanced old age, have antibodies that neutralize the H1N1 virus. "The people who have high antibody titers are the people born before 1918," he notes.

Kawaoka says that while finding the H1N1 virus to be a more serious pathogen than previously reported is worrisome, the new study also indicates that existing and experimental antiviral drugs can form an effective first line of defense against the virus and slow its spread.

There are currently three approved antiviral compounds, according to Kawaoka, whose team tested the efficacy of two of those compounds and the two experimental antiviral drugs in mice. "The existing and experimental drugs work well in animal models, suggesting they will work in humans," Kawaoka says.

Antiviral drugs are viewed as a first line of defense, as the development and production of mass quantities of vaccines take months at best.

In addition to his appointment at UW-Madison, Kawaoka also is a professor at the University of Tokyo. The new study was funded by grants from the U.S. National Institutes of Health, and the Japanese Ministry of Education, Culture, Sports, Science and Technology.

Caption: The pandemic H1N1 flu virus (red) has been shown to be more virulent than scientists previously believed. The filamentous shape of the virus, which in this image have recently budded from infected cells, is also unusual.

© 2009 Steven S. Clark, PhD, some rights reserved.  Articles contained herein, are meant to be distributed freely to interested parties. However, any use, including excerpts from any article, must credit Steven S. Clark and provide a link to the original article published in BioScience Biz.

Disclaimer: The authors used their best efforts in collecting and preparing the information published herein. However, neither Steven S. Clark, nor other authors, assume, and hereby disclaim, any and all liability for any loss or damage caused by errors or omissions, whether such errors or omissions resulted from negligence, accident, or other causes.

VC funding is up for 2Q 2009

OnBioVC.com recently reported on the trends of international VC bioscience funding for the 2Q 2009 and found that there were 88 financings for 2Q09 versus 71 deals in 2Q08. The combined second quarter 2009 bioscience investment totaled approximately $1.7B, an increase of roughly $538.2M compared to the second quarter of 2008, or a ~31% boost.

Other tidbits follow:

• The largest deal of 2Q09 went to Boulder, CO-based Clovis Oncology which closed a $145M Series A financing (really!).


• In the three month period, 11cardiovascular device deals closed, accounting for $178.9M

• There were 41 total device deals representing 47% of 2Q09 financing.

• California continued its dominance in attracting investment dollars. The state was home to 22 financings for 2Q09 for a total of $493.2M.

• After California, the most active region was outside the US where 13 financings added up to $167.5M in investment.

• The biopharma sector attracted the most investment dollars ($868.2M), narrowly out-raising medical device deals ($743.6M).

• Biofuels accounted for $85.0M and diagnostic deals raised $16.8M.

Read the entire report here.