ON TARGET
COMPLIMENTARY NEWS LETTER OF TARGET HEALTH® INC.
20 May 2007
I. WHAT'S NEW?
ASCO Meeting - Chicago
II. QUIZ - (Fill
In The Blanks)
Mouse Baldness Treatment - Hope For Humans
III. HISTORY OF MEDICINE
Babinski Reflex
IV. RHEUMATOLOGY
Genetic Basis for Rheumatoid Arthritis
V. PSYCHOSOMATIC
MEDICINE
Immune Function Declines With Unemployment
VI. EPIDEMIOLOGY
Low Glycemic vs. Low Fat Diets - Not a Simple Matter
VII. REGULATORY AFFAIRS
New
Drug Patch for Parkinson's Disease
VIII.
ASCO
Meeting - Chicago
Dr. Jules Mitchel, President of
Target Health, will be attending the annual ASCO meeting being held in
This year we managed a
successful program in pancreatic cancer, including regulatory affairs,
monitoring, data management, EDC (Target e*CRF), biostatistics and medical
writing. Our good friend, Dr. Terry Plasse was the Medical Monitor and did a
terrific job. We are currently doing EDC for a large global program in prostate
cancer.
For more information about
Target Health, please contact Dr.
Jules T. Mitchel.
Visit our Blog and Website.
II. QUIZ (Fill In The
Blanks)
Mouse
Baldness Treatment - Hope For Humans
Scientists at
the U. of Penn School of Medicine have found that hair 1) ___ in adult mice
regenerate by re-awakening genes once active only in developing embryos. These
findings provide unequivocal evidence that, like other animals such as newts
and salamanders, mammals have the power to 2) ___. A better understanding of
this process could lead to novel treatments for hair loss, other skin and hair
disorders, and wounds. It was shown, that 3) ___ healing triggered an embryonic
state in the skin which made it receptive to receiving instructions from wnt
proteins, which are a network of proteins implicated in hair-follicle
development. It was previously believed that adult mammal 4) ___ could not
regenerate hair follicles, and that, mammals had no true regenerative
qualities. However, researchers found that wound healing in a mouse model
created an "embryonic window" of opportunity. Dormant 5) ___
molecular pathways were awakened, sending stem cells to the area of injury.
Unexpectedly, the regenerated hair follicles originated from non-hair-follicle
6) ___ cells. Scientists, now, can influence wound healing with wnts or other
7) ___ that allow the skin to heal in a way that has less scarring and includes
all the normal structures of the skin, rather than just a scar. By introducing
more wnt proteins to the wound, the researchers found that they could take
advantage of the embryonic 8) ___ to promote hair-follicle growth, thus making
skin regenerate instead of just repair. Conversely by 9) ___ wnt proteins, they
also found that they could stop the production of hair follicles in healed
skin. In fact, increased wnt signaling 10) ___ the number of new hair
follicles. This suggests that the embryonic window created by the wound-healing
process can be used to manipulate hair-follicle regeneration, leading to novel
ways to treat hair loss and hair overgrowth. (Source: Nature 17 May 2007).
ANSWERS: 1)
follicles; 2) regenerate; 3) wound; 4) skin; 5) embryonic; 6) stem; 7)
proteins; 8) genes; 9) blocking; 10) doubled
III. HISTORY OF MEDICINE
Babinski Reflex
Joseph Francois Felix
Babinski, of French descent, (1857-1932), had a thorough training in general
medicine before entering the study of neurology. His bibliography is lengthy
beginning with a treatise on typhoid fever (1882) and ending with a study on
hysteria (1930). He worked with the great in neurology in
IV. RHEUMATOLOGY
Genetic Basis for Rheumatoid
Arthritis
The MHC class ll
are cell surface molecules which perform an essential function in immunological
detection using T-helper cells. They are encoded by the genes HLA-DR, -DQ and
-DP. Each MHC molecule consists of a a- and a b-chain. In the case of the DR
molecule, the two chains are encoded by the genes HLA-DRA and HLA-DRB1.
However, only DRB1 is polymorph i.e. only this gene has a number of different
alleles existing in the population. In addition, each individual possesses two
DRB1 alleles, one from each parent. The serological typification of the DR
alleles leads to the differentiation between 10 different classes,
HLA-DR1-DR10. Until now, 33 subtypes of DR4 have been described, and are termed
HLA-DRB1*0401-*0433. Rheumatoid arthritis (RA) or chronic polyarthritis is an
intermittent systemic autoimmune disease which occurs in approx. 1% of the
population. The aetiology of the disease is unknown. It has been shown for some
time by numerous studies that there is a genetic disposition for RA caused by
several alleles of the HLA-DRB1 region. RA is associated with the HLA- DRB1*04
subtypes DRB1*0401, *0404, *0405, *0408 and also, in some different ethnic
groups with the subtypes DRB1*0101, *0102 and DRB1*1001. It is not known how
the shared epitope in HLA-DRB1*04 supports the development of RA. According to
an article published in Arthritis & Rheumatism (2007;56:1408-1416), a study
was performed to determine whether the HLA-DRB1 shared epitope (SE) is associated
with early mortality and specific causes of death in RA. For the study,
HLA-DRB1 genotyping was carried out on blood samples from 767 patients
recruited for the Early RA Study (ERAS), a multicenter, inception cohort study
with followup over 18 years. Dates and causes of death (n = 186) were obtained
from the Office of National Statistics. Results showed that the SE was not
significantly associated with overall mortality. However, the presence of 2 SE
alleles was associated with risk of mortality from ischemic heart disease
(hazard ratio [HR] 2.02, P = 0.04), and malignancy (HR 2.18, P = 0.01).
Analysis of specific SE genotypes (corrected for age and gender) revealed that
the HLA-DRB1*0101/*0401 and 0404/*0404 genotypes were the strongest predictors
of mortality from ischemic heart disease (HR 5.11 and HR 7.55, respectively),
and DRB1*0101/*0401 showed a possible interaction with smoking. Male gender,
erythrocyte sedimentation rate, and Carstairs Deprivation Index were also
predictive, but the Health Assessment Questionnaire score, rheumatoid factor,
nodules, and swollen joint counts were not. Mortality due to malignancy was
particularly associated with DRB1*0101 genotypes. According to the authors, The
risk of mortality due to ischemic heart disease or cancer in RA is increased in
patients carrying HLA-DRB1 genotypes with particular homozygous and compound
heterozygous SE combinations.
V. PSYCHOSOMATIC
MEDICINE
Immune Function Declines With
Unemployment
Natural Killer (NK) cells are an
important part of our immune system and are another type of lethal lymphocyte.
Like cytotoxic T cells, they contain granules filled with potent chemicals.
They are called "natural" killers because they, unlike cytotoxic T
cells, do not need to recognize a specific antigen before swinging into action.
They target tumor cells and protect against a wide variety of infectious
microbes. In several immunodeficiency diseases, including AIDS, natural killer
cell function is abnormal. Natural killer cells may also contribute to immunoregulation
by secreting high levels of influential lymphokines. Both cytotoxic T cells and
natural killer cells kill on contact. The killer binds to its target, aims its
weapons, and then delivers a lethal burst of chemicals that produces holes in
the target cell's membrane. Fluids seep in and leak out, and the cell bursts.
According to an article published in Psychosomatic Medicine (2007;69:225-234
(2007), a study was performed to examine the effect of unemployment on natural
killer cell cytotoxicity (NKCC). The study also followed a subsample of persons
who become re-employed, to determine if, after termination of the stressor,
immune values recover to levels similar to matched controls. For the study, 100
unemployed and 100 matched employed healthy men and women, aged 29 to 45 years,
were followed for 4 months with monthly blood samples taken to measure NKCC.
Twenty-five participants obtained employment before the end of the study,
leaving 75 unemployed (and 75 employed) participants in the main sample. For unemployed
participants who obtained employment before the end of the study, subsample
analyses compared NKCC levels before and after obtaining a new job. Results
showed that the persistently unemployed sample had significantly lower NKCC
levels when compared with the matched employed sample. There were no
significant gender effects. In the subsample analyses, NKCC was significantly
higher after the participants became employed, compared with their unemployed
period, with substantial "recovery" of immune function (44%–72%)
compared with values from the steadily employed group. According to the
authors, chronic stress is associated with persistent NKCC impairment. However,
when the chronic stressor is terminated, the immune cell functional capacity
quickly begins to recover. The authors added that this is the first study in
humans to document immune function recovery after the definable end of a
chronic stressor.
VI. EPIDEMIOLOGY
Low Glycemic vs. Low Fat
Diets - Not a Simple Matter
The results of
clinical trials involving diet in the treatment of obesity have been
inconsistent, possibly due to inherent physiological differences among study
participants. As a result, a study published in the Journal of the American
Medical Association (2007;297:2092-2102), was performed to determine whether
insulin secretion affects weight loss with 2 popular diets. The diets included
a low–glycemic load (40% carbohydrate and 35% fat) vs. low-fat (55%
carbohydrate and 20% fat). The investigation was a randomized trial of obese
young adults (aged 18-35 years; n = 73). The study consisted of a 6-month
intensive intervention period and a 12-month follow-up period. Serum insulin
concentration at 30 minutes after a 75-g dose of oral glucose was determined at
baseline as a measure of insulin secretion. Outcomes were assessed at 6, 12,
and 18 months. The main outcome measures were changes in body weight, body fat
percentage determined by dual-energy x-ray absorptiometry, and cardiovascular
disease risk factors. Results showed that changes in body weight and body fat
percentage did not differ between the diet groups. However,
insulin concentration at 30 minutes after a dose of oral glucose did have an
effect. For those with insulin concentration at 30 minutes above the median
(57.5 µIU/mL), the low-glycemic load diet produced a greater decrease in weight
(-5.8 vs. -1.2 kg; P = .004) and body fat percentage (-2.6% vs -0.9%; P = .03)
than the low-fat diet at 18 months. There were no significant differences in
these end points between diet groups for those with insulin concentration at 30
minutes below the median level of 57.5 µIU/mL. In the full population, plasma
high-density lipoprotein cholesterol and triglyceride concentrations improved
more on the low-glycemic load diet, whereas low-density lipoprotein cholesterol
concentration improved more on the low-fat diet.
VII. REGULATORY AFFAIRS
TARGET HEALTH excels in
Regulatory Affairs and works closely with many of its clients performing all
FDA submissions. TARGET HEALTH receives daily updates of new developments at
FDA. Each week, highlights of what is going on at FDA are shared to assure that
new information is expeditiously made available.
New Drug Patch for
Parkinson's Disease
More than 1
million Americans live with Parkinson's disease (PD) and 60,000 new cases are
diagnosed each year. PD, which belongs to a group of conditions called motor
system disorders, results from the loss of dopamine-producing brain cells. The
four primary symptoms of Parkinson's are trembling in hands, arms, legs, jaw,
and face (tremor); stiffness of the limbs and trunk (rigidity); slowness of
movement (bradykinesia); and impaired balance and coordination (postural
instability). As these symptoms become more pronounced, patients may have
difficulty walking, talking, or completing other simple tasks. The FDA
announced the approval of Neupro (rotigotine transdermal system), a new
chemical entity (NCE) skin patch designed to treat symptoms of early PD. Neupro
is the first transdermal patch approved for the treatment of symptoms of PD.
Rotigotine, a member of the dopamine agonist class of drugs, is delivered
continuously through the skin (transdermal) using a silicone-based patch that
is replaced every 24 hours. A dopamine agonist works by activating dopamine
receptors in the body, mimicking the effect of the neurotransmitter dopamine.
The effectiveness of Neupro was demonstrated in one fixed-dose response study
and two flexible-dose studies. The parallel group studies were randomized,
double-blinded, and placebo-controlled, and involved 1,154 patients with early
Parkinson's disease who were not taking other Parkinson's medications. The most
common side effects for Neupro included skin reactions at the patch site,
dizziness, nausea, vomiting, drowsiness and insomnia, most of which are typical
of this class of drugs. Other potential safety concerns include sudden onset of
sleep while engaged in routine activities such as driving or operating
machinery (sleep attacks), hallucinations, and decreased blood pressure on
standing up (postural hypotension). Neupro Patch is manufactured by Schwarz
Bioscience of Research Triangle Park, N.C.
For more information about
our expertise in Regulatory Affairs, please contact Dr. Jules T. Mitchel or Dr.
Glen Park.
VIII. TARGET HEALTH
TARGET HEALTH INC. (www.targethealth.com) is a
full service eCRO with full-time staff dedicated to all aspects of drug and
device development. Areas of expertise include Regulatory Affairs, comprising,
but not limited to, IND, IDE, NDA, PMA and 510(k) submissions, execution of
Clinical Trials, Project Management, Biostatistics and Data Management, Web
Trials, utilizing Target e*CRF®, our proprietary Internet-based Clinical Trial
System, and Medical Writing. TARGET HEALTH's Pharmaceutical Advisory Dream Team
(PADT) assists companies in strategic planning from Discovery to Market Launch.
Let us help you on your next project.
TARGET HEALTH INC.
261 Madison Avenue
24th Floor
New York, NY 10016
Phone: (212) 681-2100; Fax (212) 681-2105
http://blog.targethealth.com
www.targethealth.com
Dr. Jules T. Mitchel,
President
Ms Joyce Hays, CEO
©2007 Target Health Inc. All rights reserved
