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Online Update Page, January 11, 2006
Clinical trials
Drug companies offer
more details on clinical trials
More clinical trials — including those involving drugs under development —
are being registered in a national database, according to a study appearing in
the Dec. 29, 2005, issue of the “New England Journal of Medicine” (NEJM).
Recent safety problems with high-profile drugs, such as, GlaxoSmithKline’s (GSK)
anti-depressant Paxil (paroxetine) and Merck’s painkiller Vioxx
(rofecoxib) have highlighted the importance of making public the information
coming out of research trials involving medications, the researchers said.
But the researchers also noted a mixed reaction to the enhanced clinical trial
disclosure — while some experts are especially concerned about the moral and
safety implications of apparently withholding information from people who
willingly participate in these trials, many companies conducting the trials are
balking at the idea of making proprietary information available before a drug is
fully developed.
In the U.S., the FDA Modernization Act of 1997 requires that all private and
public trials that involve treatment of “serious or life-threatening
conditions” under IND protocol be registered. Additionally, ClinicalTrials.gov
was established in 2000 as a result of this law; the database allows the
registration of any clinical trial, not just those mandated by the modernization
act.
Moreover, on Sept. 13, 2005, a policy set forth by the International
Committee of Medical Journal Editors (ICMJE) was implemented. The policy
improved clinical trial disclosure for researchers even further by requiring the
registration of clinical trials if they are to be considered for publication.
In an Oct. 11, 2005, study by ICMJE, the authors assessed information in
ClinicalTrials.gov from May 20 to the Sept. 13 implementation of the ICMJE
policy. During that period, the number of registrations increased by 73% —
from 13,153 to 22,714. Clearly, the ICMJE policy had an effect.
Furthermore, the percentage of trials with nonspecific entries in the “intervention
name” field — such as, drugs, surgical procedures or devices — decreased
from 10% to 2%. According to ICMJE, these data changes were attributable to
large drug companies, such as, GSK, Merck, Novartis and Pfizer.
All other records contained specific entries in this field, the study found.
Some large pharmaceutical companies “provided meaningful entries in the
intervention name field in an astonishingly low number of registrations,” said
Jeffrey Drazen, M.D., editor-in-chief, ICJME.
By October 2005, according to Drazen, Novartis had completed this field
only 3% of the time and Merck only 20% of the time, even though many of their
competitors were in full compliance.
Merck eventually “cleaned up its act” by updating most of its entries. The
other companies have not shown the same improvements, Drazen noted.
Of the 2,670 studies registered by industry during the time interval, 76%
provided information in the “primary outcome measure” field, although the
entries varied in terms of how specific they were. The field was blank in the
remaining 24% of records. Before May 20, 2005, according to the authors, this
field was usually left blank. Now the information is more likely to be left out
for Phase IV trials.
“We need people to fill out all the fields in a meaningful fashion,” Drazen
said. Everyone ought to know what’s going on.”
Asked to comment on the study findings, Merck offered this statement: “Merck
is pleased that the article published in this week’s issue of the NEJM
acknowledges the progress that we have made in the registration of clinical
trials on ClinicalTrials.gov.
"As we’ve said many times, Merck is committed to registering all Phase
II, III and post-marketing controlled clinical trials and we have done so, as
evidenced by the NEJM article.”
One question not addressed by the study, however, is how useful even complete
information will be to the layperson, noted Mark Fendrick, M.D., a professor of
internal medicine at the University of Michigan School of Medicine.
“What remains to be seen is whether the information entered into these
registries actually become useful down to the level of the individual,” said
Fendrick. “Hopefully, the infrastructure is behind this to make it
user-friendly.”
Two research centers
join NIDA clinical trials network
National Institute on Drug Abuse (NIDA) announced Jan. 5 it has established two
new clinical trials network (CTN) affiliates. This development increases the
range of NIDA’s research infrastructure to test drug-addiction treatments in
real-life settings with diverse patient populations.
According to the NIH press release, the new nodes are:
These new nodes join 15 existing nodes, not
listed in the press release, and bring the total number of community-based
treatment programs to approximately 150.
Since its inception just six years ago, 16 protocols have completed enrolment of
over 5,000 patients in 103 community-treatment programs in over 20 states. Five
additional protocols currently are recruiting and enrolling an estimated 2,200
participants across 38 community-treatment programs.
Additionally, scientists have completed data collection for nine protocols; and,
five new protocols are currently being developed. NIDA and other components of
Public Health Service are now preparing local treatment centers for adoption of
CTN-proven interventions.
Stem
cell research
Stem cells treat
blood disorder
Scientists in the U.S. say they have successfully corrected a genetic mutation
that causes the blood disorder sickle cell anemia. A team from University of
California, San Francisco carried out the repair on stem cells taken from
embryonic mice.
The San Francisco team worked on embryonic stem cells carrying the human sickle
cell mutation. Sickle cell, which primarily affects people of African,
Mediterranean, Middle Eastern and Indian descent, can cause circulation
problems. The genetic mutation results in an abnormal form of hemoglobin, the
molecule within red blood cells that carries oxygen. This causes the blood cells
to assume a sickle shape and stick together, which means blood cannot circulate
properly.
Essentially, the researchers inserted a healthy copy of the hemoglobin gene,
replacing the mutated version. This insertion generated stem cells carrying
sickle cell trait, but not full-blown sickle cell.
The researchers said they eventually hope to be able to genetically alter human
embryonic stem cells from a patient’s own DNA and transplant them back into
the patient, correcting their sickle cell anemia. Additionally, they believe,
the same stem cell gene therapy could be used to cure another genetic blood
disorder, thalassemia.
South Korean
stem-cell researcher resigns
South Korean researcher Hwang Woo-suk
resigned from his university — Seoul National University — Dec. 23,
2005, after the school confirmed that he fabricated stem-cell research that had
raised hopes of new cures for hard-to-treat diseases.
A university panel, releasing initial findings of a probe, accused Hwang of
damaging the scientific community with his deception, while South Korea’s
government lamented the scandal surrounding the country’s star scientist and
said it may pull its funding for his research.
“With an apologetic heart ... I step down as professor,” Hwang said. However, Hwang still contends that
he had produced the technology to create patient-matched stem cells as he
claimed in a May article in the journal “Science.”
“I emphasize that patient-specific stem cells belong to South Korea and you
are going to see this,” said
Hwang, a veterinarian, emphasized to the press.
On Dec. 23, 2005, the panel of Seoul National University experts said Hwang had
faked results of at least nine of 11 stem cell lines he claimed to have created
in the May paper. This is the first public confirmation of the allegations that
have cast a shadow over the university’s purported breakthroughs in cloning
and stem-cell technology.
“This kind of error is a grave act that damages the foundation of science,”
the panel concluded.
The South Korean government, which had strongly supported Hwang and designated
him the country’s first “top scientist,” said it was “miserable” over the reported results of the
investigation and will start its own probe over ethics breaches.
Research and development
U.S. research budget
worries scientists
The realignment by Congress of research money toward national defense and human
space exploration means many universities, institutions and scientists will have
to scramble for new sources of money or cut back current or planned projects.
For example, NIH, the nation’s premier biomedical research agency, saw its
budget doubled between 1999 and 2003 but is getting $28.6 billion next year, a
slight 0.1% drop that marks its first budget cutback since 1970.
The cut, although small, comes at a time when a lot of research simply costs
more, even the laboratory mice used in cancer research, explained Harold Varmus,
M.D., a former NIH director and Nobel Prize winner.
“There is a battle for the future in science and technology. That’s what is
going to govern the future of our country. Not increasing investments in those
areas sends a signal the country is going to regret,” said Varmus, who now
heads the Memorial Sloan-Kettering Cancer Center in New York.
But the Bush administration believes it is doing its best for research and
development, countering that federal spending remains near an all-time high and
is close to 45% higher than when the president took office.
That “is a strong statement of the high priority this administration places on
innovation, competitiveness, science, technology and research,” said Donald
Tighe, a spokesperson for Office of Science and Technology Policy, which advises
the president.
However, according to an analysis by the American Assn for the Advancement of
Science, although federal research and development spending will rise $2.2
billion, or 1.7%, in 2006, to about $135 billion, of that increase, 97% will go
to Department of Defense weapons development and National Aeronautics and Space
Administration spacecraft programs.
Most immediately, decreased R&D spending will lead to layoffs and other
cutbacks at some facilities that rely on federal funding. “A lot of innovation
comes from basic research, and it takes a number of years for that basic work to
transform itself into innovations,” added Sam Rankin, associate executive
director of the American Mathematical Society and chair of the Coalition
for National Science Funding.
GenVec completes
previously announced sale of myoblast cell therapy program
GenVec, Gaithersburg, MD, announced Dec. 29, 2005, the sale of its myoblast
cell therapy program to Mytogen, Charleston, MA — a newly-formed
private biotechnology company specializing in cell therapy products.
In October, GenVec announced its intention to sell the myoblast program in order
to focus its resources on the development of its core product candidates.
Mytogen also will acquire the assets and technology that had supported this
program and retain the majority of employees who managed it.
Mytogen said it also intends to continue to provide cells and clinical supplies
necessary to finish the ongoing investigator-sponsored myoblast clinical trial
at the Arizona Heart Institute.
GenVec said this will allow the company to focus on the development of TNFerade,
its lead oncology product program. GenVec acquired the myoblast program through
its merger with Diacrin, Inc., Charleston, MA, in 2003.
“The sale of the cell therapy program will provide a new source of funding for
this program, allow us to focus more of our resources on later-stage development
programs and save GenVec nearly $3 million annually,” said Paul Fischer,
Ph.D., president and CEO, GenVec.
“We wish Mytogen success in the development of this promising cell therapy for
the treatment of congestive heart failure.”
GenVec is a publicly held clinical-stage biopharmaceutical company focused on
the development and commercialization of novel therapies that improve patient
care in the areas of cancer and cardiac disease, and to prevent vision loss.
Each of GenVec’s gene-based product candidates uses a common patent-protected
platform to deliver genes that produce medically beneficial proteins directly at
the site of disease — TNFerade for oncology, Biobypass for cardiovascular
disease, and AdPEDF for ophthalmology.
Furthermore, GenVec’s vaccine program applies the company’s unique delivery
technology and 293-ORF6 cell line to develop vaccines against a variety of
diseases, including HIV, malaria, and foot and mouth disease.
FDA
management
CDER to foster
research, communication with AHRQ
Beginning in mid-January, Anne Trontell, M.D., Captain, U.S. Public Health
Service; and deputy director, Office of Drug Safety, CDER, will embark on a
12-month detail to the Agency for Healthcare Research and Quality (AHRQ)
to serve as a senior advisor in pharmaceutical outcomes research in Center for
Outcomes and Effectiveness (COE), Center for Drugs announced Jan. 4.
According to the press release, Trontell will foster research and collaboration
between FDA and AHRQ on drug effectiveness and safety. She also will participate
in effectiveness and risk-communication research and outreach conducted by the
new AHRQ Effective Health Care Program, which was authorized under the Medicare
Modernization Act.
Additionally, while at COE, Trontell will participate in developing its
pharmaceutical outcomes, research agenda in drug effectiveness and safety, and
in cultivating research partnerships in these areas between AHRQ, FDA, Centers
for Medicare and Medicaid Services, and academic and professional organizations.
Trontell has been with Center for Drugs since 1996, first as a medical officer
in Office of New Drug’s Division of Pulmonary Drug Products, then as deputy
director of Office of Post-marketing Drug Risk Assessment’s Division of Drug
Risk Evaluation, then as director of Office of Dietary Supplements’ (ODS)
Division of Surveillance, Research and Communication Support.
Trontell became deputy director of ODS in April 2003 and has played a central
role in developing risk-minimization activities for drug safety problems. Prior
to joining FDA she led and conducted preventive health services research for
four years at Health Care Financing Administration, where she served chief
scientist for the Office of Research and Demonstrations after serving as an
Epidemic Intelligence Service Office at Centers for Disease Control and
Prevention (CDC), Office on Smoking and Health.
“Trontell’s long-standing interests in risk management and risk
communication will greatly contribute to her activities with the Effective
Health Care Program,” CDER noted. “One of the Program’s missions is to
improve the quality, speed, and uptake of health care communications to
consumers, clinicians, payers and health care policymakers by translating
findings in ways to meet the specific needs of different stakeholders.”
Effective with the start of Trontell’s detail, Jonca Bull, M.D., current
deputy director of Office of Pharmacoepidemiology and Statistical Science, also
will serve as acting deputy director for ODS.
More information about the COE program can be found at http://www.effectivehealthcare.ahrq.gov.
NCTR acting director selected
William Slikker, Jr., Ph.D., was
named as acting director of National Center for Toxicological Research (NCTR),
effective Jan. 4.
Slikker has held a variety of research and management positions within FDA, most
recently serving as the deputy center director for research, NCTR. In his new
role at NCTR, Slikker will continue to conduct peer-reviewed research targeted
to develop a scientifically sound basis for regulatory decisions and to reduce
risks associated with FDA-regulated products. This research is aimed at
evaluating the biological effects of potentially toxic chemical, biological or
physical agents and developing methods to improve assessment of human exposure,
susceptibility and risk.
Additionally, Slikker has a long-standing interest in graduate education and
holds adjunct professorships in the Departments of Pediatrics, and Pharmacology
and Toxicology at the University of Arkansas for Medical Sciences.
He also has held committee chairs or elected offices in several scientific
societies, including the Teratology Society (serving as president) and
the American Society for Pharmacology and Experimental Therapeutics (chair,
developmental pharmacology section and member of the program committee) and as
the chair of the membership committee, past president of the neurotoxicology
specialty section, and past president of the south central chapter of the Society
of Toxicology.
Slikker also is co-founder and president of the MidSouth Computational
Biology and Bioinformatics Society; and he is associate editor for the
journal “NeuroToxicology and Toxicological Sciences.”
“NCTR benefits significantly from sharing knowledge in collaborations with
scientific staff in all NCTR disciplines, other FDA Centers, and other
government agencies, academia, and industry,” said Andrew von Eschenbach,
M.D., Acting Director, FDA.
“In his new role as NCTR’s Acting Director, Dr. Slikker looks forward to
continuing his many interactions with colleagues within FDA and with other
scientists within the national and international toxicology and safety
pharmacology communities.”
People
Cooper joins
HealthPoint as director of clinical affairs, tissue management
Tissue Management for HealthPoint, Ltd., Ft. Worth, TX, a DFB
Pharmaceuticals Inc. affiliate company announced Dec. 20, 2005, that Diane
Cooper, Ph.D., joined the HealthPoint team as director of clinical affairs for
tissue management.
A recognized leader in clinical research, nursing, education and industry,
Cooper’s focus on wound healing has spanned four decades and included, among
other prestigious roles, faculty appointments in Schools of Nursing at Michigan
State University, University of California San Francisco, and the University
of Texas Medical Branch in Galveston. Cooper also served as the worldwide
medical director for Johnson&Johnson Wound Management.
“We are very honored to add Dr. Cooper to our clinical department, greatly
enriching an already exemplary tissue management team. Her knowledge and
dedication mirror and bolster HealthPoint’s commitment to serving wound care
patients,” said Michael Steadman, president of tissue management, HealthPoint.
“Dr. Cooper will play a key role in evolving our business and its clinical
leadership, resulting in tremendous impact on the future of this population
across the country.” “HealthPoint’s evidence-based products are helping
patients now, and I am delighted to be engaged in processes to further increase
innovation and consistency of care,” added Cooper.
“From the beginning, I wanted patients to heal as quickly as possible, but in
order to combat their wounds, I needed an arsenal of knowledge that, at that
time, was not readily accessible. Now, by advancing accessible clinical research
and education at HealthPoint, we can actively influence the future of wound
healing science and find practical solutions to wound healing problems.”
National Quality Care reorganizes management team to focus principally
on its wearable artificial kidney
National Quality Care, Inc., Beverly Hills, CA, Dec. 29, 2005, announced
that it has reorganized its management to focus on the development and clinical
trials of its wearable artificial kidney.
Victor Gura, M.D., the inventor of the Wearable Kidney, will become the company’s
chief scientific officer and, as such, will be able to devote himself
principally to the development of the Wearable Artificial Kidney.
Pending appointment of a replacement CEO for Gura, Robert Snukal, a director of
the company, will serve as the interim CEO and president; and Leonardo
Berezovsky, M.D., currently a director, will become chair of the board.
Additionally, Berezovsky, Snukal and Jose Spiwak, M.D., also a director of the
company, will comprise an Executive Committee, which will be responsible for
conducting the search for a permanent CEO and president, in consultation with
the company’s management, as well as for directing the management of the
company in consultation with the interim CEO and president. Berezovsky, Snukal
and Spiwak also will evaluate and direct the company’s strategic business
goals.
National Quality Care is focused principally on the development of a Wearable
Artificial Kidney that can be worn as a belt and operates 24 hours a day, seven
days a week. In addition, the company is a provider of integrated dialysis
services for patients suffering from chronic kidney failure.
UTEK appoints Blundell to scientific advisory council
UTEK Corp., Plant City, FL, announced Dec. 29, 2005, that Sir Tom
Blundell, D. Phil., joined UTEK’s scientific advisory council.
Blundell is a Sir William Dunn professor of biochemistry and head of the
department of Biochemistry at the University of Cambridge.
Blundell also was chair of the
Royal Commission on Environmental Pollution and he is a co-editor of “Progress
in Biophysics and Molecular Biology” and “Opinion in Structural Biology.”
According to the press release, Blundell is considered an expert in biological
sciences, having professional experience in the fields of biomedicine,
crystallography, structural biology and bioinformatics.
“We are most pleased to announce Professor Sir Tom Blundell’s
appointment to the Scientific Advisory Council, said Jeff Bleil, M.D., chief
technology officer and head of the scientific advisory council, UTEK.
“We believe Dr. Blundell’s breadth of knowledge, along with his interest in
commercialization of university technologies, will greatly assist us in our
technology transfer efforts.”
UTEK is a market-driven technology transfer company that enables companies to
rapidly acquire innovative technologies from universities and research
laboratories worldwide.
Trial
news updates
Adolor Corp., Exton, PA, announced Dec. 29, 2005, that it has
submitted an IND with FDA for ADL5859, a novel, oral compound that targets the
Delta opioid receptor. Delta receptor agonists are thought to offer benefits
over other approaches to the management of pain. ADL5859 will represent Adolor’s
third program in human clinical testing and is an important component of the
company’s growing pipeline. The three opioid receptors modulate pain and may
have applications in other indications, the company said. ADL5859 has shown
activity and an attractive safety profile in preclinical evaluation and is under
development for the potential relief of inflammatory and neuropathic pain. At
present, there are no selective Delta agonists approved by FDA.
Bristol-Myers Squibb announced that the company has completed submission
of its NDA to FDA for dasatinib to treat chronic myelogenous leukemia (CML) in
chronic, accelerated or blast phases, as well as Philadelphia
chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). The NDA seeks
approval of dasatinib, an investigational multi-targeted kinase inhibitor, to
treat adult CML and Ph+ ALL patients with resistance or intolerance to prior
therapy. CML is a slowly progressing cancer of the blood and bone marrow that
usually occurs during or after middle age and rarely occurs in children. ALL is
a rapidly progressing cancer of the blood and bone marrow that usually occurs in
children, although it can occur at any age.
Genta, Berkeley Heights, NJ, Dec. 29, 2005, announced that the
company has completed the filing of an NDA for its lead anticancer drug,
Genasense (oblimersen sodium) Injection. The application proposes the use of
Genasense plus fludarabine and cyclophosphamide as treatment for patients with
relapsed or refractory chronic lymphocytic leukemia. The NDA — which was
submitted pursuant to FDA’s fast track and accelerated approval designations
— contains safety and efficacy data from a disease-specific Phase I/II trial
of Genasense used alone that enrolled approximately 40 patients, as well as a
randomized, controlled Phase III study of 241 patients who received fludarabine
and cyclophosphamide with or without Genasense. These data are supplemented by
safety data derived from approximately 1,000 additional patients who have
received Genasense in other clinical trials. The pivotal Phase III trial was
designed to test whether the addition of Genasense to standard chemotherapy
would significantly increase the proportion of patients who achieved a complete
or nodular partial response (CR/nPR). That trial met its primary endpoint: the
addition of Genasense increased the proportion of patients who achieved CR/nPR
from 7% in the chemotherapy-only arm to 17% in the Genasense arm (P=0.025). The
company said all CR/nPRs in both trial arms were durable (i.e., exceeding six
months in minimum duration). However, extended follow-up of patients enrolled in
the trial showed that the duration of CR/nPR was significantly longer in
patients treated with Genasense compared with patients who received chemotherapy
only. The median duration of CR/nPR was 22 months for the chemotherapy-only
group, whereas the median has not yet been reached in the Genasense group
(P=0.03). The achievement of CR/nPR was associated with substantial clinical
benefit, including but not limited to relief of all disease-related symptoms and
normalization of blood counts.
GW Pharmaceuticals, London, said Jan. 4 it has won approval from FDA to
conduct a pivotal Phase III study into its cannabis-based medicine Sativex as a
treatment for cancer pain. GW said it expects to start testing the product,
which is sprayed into the mouth, in U.S. patients with advanced cancer later
this year and said it was raising $15 million in a discounted share placing to
help fund the trial while its looks for a U.S. partner. The randomized clinical
trial will involve 250 people and is likely to last between 24 and 36 months,
suggesting Sativex will not be ready for launch in the U.S. marketplace until
toward the end of the decade. Canada became the first country in the world to
approve Sativex in April 2005, for the relief of neuropathic pain in patients
with multiple sclerosis. GW suffered a setback in December 2005, however, when a
British inquest found the death of a patient taking Sativex in an earlier
clinical study was probably linked to the medicine.
Trial
briefs
AVI BioPharma, said Jan. 10 that its experimental hepatitis C virus (HCV)
treatment appeared active and safe in the first stage of a study. The company
said similar drugs developed by other companies have often been limited by
serious side effects at higher doses. The drug firm tested the treatment, called
Neugene, on 30 healthy volunteers at three dosage levels. AVI said there were no
serious side effects, adding that the drug reached its heaviest blood
concentration in about four hours after injection. AVI said it plans to continue
the study with a target dose between 100 mg and 300 mg. The company tested doses
of 50 mg, 100 mg and 300 mg. The second phase of the study will include up to 40
patients with chronic, active HCV. The disease is characterized by liver
inflammation and can eventually lead to liver cancer or failure.
Group Health Cooperative researchers — a group of researchers from 14
institutions — said U.S. studies indicated that
anti-depressants work for some. Specifically, the findings, which were published
in the January issue of the “American Journal of Psychiatry,” showed that
suicidal behavior among adults taking anti-depressants dropped almost as soon as
they began treatment with selective serotonin reuptake inhibitors (SSRIs). The
researchers believe their findings confirm SSRI effectiveness in older patients.
The decline was especially significant among patients taking newer drugs to
treat depression. The findings are promising, coming at a time when some experts
grapple with whether such drugs can provoke suicidal tendencies, the Cooperative
noted. In 2004, FDA concluded there was a higher risk of suicidal behavior among
children and teenagers and ordered strong label warnings. However, after
reviewing more than 65,000 patient records from 1992 to 2003, researchers in
Seattle found fewer suicide attempts or deaths after patients began medication.
In the six months after medication, there were 76 attempts severe enough to
require a hospital visit compared with 73 attempts in the three months prior.
Adolescents showed more attempts than adults, but there was not enough data for
a strong conclusion. About 6% of patients were 17 and younger, according to a
study funded by National Institute of Mental Health (NIMH). The NIMH researchers
had reviewed records from the Group Health Cooperative health plan.
Novartis Institute for Tropical Diseases, Singapore, and National
Institute of Allergy and Infectious Diseases (NIAID) scientists said they
have determined how a promising drug candidate attacks the bacterium that causes
tuberculosis (TB). Published online in the Dec. 26, 2005, issue of the “Proceedings
of the National Academy of Sciences,” the finding may help scientists optimize
the drug candidate, PA-824, which targets Mycobacterium tuberculosis (M.
tb). According to the scientists, in preclinical testing, PA-824 showed
evidence of being effective against both actively dividing and slow-growing M.
tb, giving rise to optimism that the compound may be useful in treating both
active and latent TB. The scientists explained that they approached the problem
indirectly by searching for M. tb mutants that resisted the killing power
of PA-824. The team confirmed previous research suggesting that resistance
usually occurs when M. tb lacks components called FGD1 and F420, neither
of which interacts directly with the drug. Next, the investigators screened for
PA-824-resistant M. tb that retained sensitivity to a close relative of
PA-824. Within this subgroup of PA-824-resistant bacteria, the team identified
those mutant strains with FGD1 and F420. The investigators reasoned that
resistance to PA-824 in mutants possessing FGD1 and F420 must be due to a
mutation in the M. tb protein that directly interacts with PA-824. But
determining exactly which of M. tb’s thousands of proteins was changed
in these mutants proved difficult; conventional genetic techniques for comparing
normal and mutant strains of M. tb failed, so the team turned to a
specially modified microarray-based technique, called comparative genome
sequencing, developed by NimbleGen Systems, Madison, WI. This was the
first time the technique had been used to identify a protein involved in TB drug
resistance. Using the NimbleGen technique, which effectively re-sequences the
entire genome of the bacterium, the scientists quickly pinpointed the protein
altered in the PA-824-resistant mutant strains of M. tb. In the past,
such a complete genome comparison might have taken many months of work; this new
technology enables scientists to zero in on the specific genetic difference
between mutant and normal bacterial strains in just days, the researchers noted.
The scientists found a total of four PA-824-resistant mutant strains: two lacked
the newly described M. tb protein altogether, while the remaining two
mutants evidently acquired resistance to PA-824 through a mutation that made the
protein unable to bind to the drug. With the discovery of the specific protein
that interacts with PA-824, Novartis Institute and NIAID researchers said they
now have information they can use to produce improved PA-824 relatives and
accelerate the pace of new TB drug development.
Conferences
Clinical Data Disclosure and the Pharmaceutical Image, Jan. 17-18, Washington.
For more information, visit http://www.exlpharma.com/events/ev_descrip.php?ev_id=23.
Upcoming Society of Clinical Research Associates (SoCRA) programs. For
more information, visit http://www.SoCRA.org.
Lab
Automation 2006 , 10th Annual Conference and Exhibition on Emerging
technologies, Jan. 21-25, Palm Springs, CA Sponsored by the Assn. for Laboratory Automation. For
more information, visit http://labautomation.org/LA/LA06/index.php.
Drug Development Summit: R&D
Innovation, Acceleration & Risk Management, Feb.
12-15, Phoenix. For more information, visit http://www.drugdevelopmentsummit.com.
CHI’s 13th International Molecular Medicine Tri-Conference, Feb. 21-24, Moscone
North Convention Center, San Francisco. For more information, please visit
Commercial Implications of Stem Cell Research, Feb. 22-24,
Moscone North Convention Center, San Francisco. Sponsored by Cambridge
Healthtech Institute. For more information, visit http://www.tri-conference.com/track6_STM.asp.
15th Annual Partnership with CROs, April 3-5, The Mirage
Hotel, Las Vegas. For more information, visit http://www.iirusa.com/cropartners/index.cfm.
12th National HIPAA Summit, April 9-11, Hyatt Regency on
Capitol Hill, Washington. For more information, visit http://www.HIPAASummit.com.
Note from the Editors: there
will be no Bioresearch Compliance Report — The
Insider’s Guide to GCP and GLP Compliance and Enforcement online
next week, Jan. 17, because out print edition will come out that week. The next
online edition you receive will be on Jan. 24.
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