DECember
2 012
Carolina Partners in Mental HealthCare Leading the Way with Cutting-Edge Care and New TMS Therapy for Depression
T H E M A G A Z I N E F O R H E A LT H C A R E P R O F E S S I O N A L S
Also in This Issue Prenatal Surgery Online Practice Marketing
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Innovating for life.
COVER STORY
6 dece m b e r
Carolina Partners in Mental HealthCare
Leading the Way with Cutting-Edge Care and New TMS Therapy for Depression 2012
V o l . 3 , I s s u e 11
FEATURES
10
Fetal Surgery
In-utero Surgery for Spina Bifida to Improve Postnatal Outcome Dr. William Goodnight III examines the incidence of spina bifida and the effectiveness of prenatal repair.
14
DEPARTMENTS 9 Women’s Health A New Way to Conquer Weight Gain
15 Duke News
- Hospital Names New President - Aerobic Exercise Is Better for Weight and Fat Loss Than Resistance Training
17 Duke Research News Fragile X Protein Is Linked to Nearly 100 Genes Involved in Autism
18 UNC Research News Practice Management
Reasons Why Online Marketing Should Be in Your Marketing Plan Amanda Kanaan reviews the cost-effective benefits of online marketing to medical practices, regardless of size.
Gene Therapy Cocktail Shows Promise for Children with Fatal Brain Disease
19 UNC Research News Designer Drugs Effectively Hit Multiple Protein Targets At Once
20 News Welcome to the Area - New MDs and PAs
COVER PHOTO: Sandeep Vaishnavi, M.D., Ph.D.; Rohima Miah, M.D.; and Robyn Gaylor, (sitting) of Carolina Partners in Mental HealthCare demonstrate the use of transcranial magnetic stimulation (TMS) therapy.
2
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From the Editor
From the Editor Renewed Hope Depression is a devastating illness that can erode all aspects of one’s life, including one’s physical health, and in rare cases may be the catalyst of dreadful criminal acts. Mental health practitioners have been challenged by treatment options that center on antidepressants, whose benefits have proven to be elusive.
T H E M A G A Z I N E F O R H E A LT H C A R E P R O F E S S I O N A L S
The practitioners at Carolina Partners in Mental HealthCare – our cover story this month – have embraced transcranial magnetic stimulation, or TMS therapy, recently approved by the United States Food and Drug Administration for major depressive disorder. TMS was developed in 1985 as an alternative to direct electrical stimulation of neurons. Since then, extensive research has shown improved efficacy that could lead to reduced use of antidepressants.
Editor Heidi Ketler, APR
Also in this year’s final issue of The Triangle Physician, we bring you Dr. William Goodnight, who presents a fascinating column on the use of in-utero surgery to improve spina bifida outcomes.
Photography Mark Jacoby
Obstetric gynecologist Andrea Lukes returns to discuss the virtues of a new weightloss drug. Practice marketing specialist Amanda Kanaan advises that marketing plans should now incorporate the various online tools. It is impossible to write this, following the tragedy in Newtown, Conn., without a note of sorrow. People the world over are grieving for the families and questioning the plight of humanity. I would like to share where I found solace – I reached out to my sister, a preschool teacher in Chardon, Ohio. She shared with me what she had already sent her students’ parents – words from Fred Rogers, with whom she and I grew up. May you also find the words of Mr. Rogers helpful: “When I was a boy and I would see scary things in the news, my mother would say to me, ‘Look for the helpers. You will always find people who are helping.’ To this day, especially in times of disaster, I remember my mother’s words, and I am always comforted by realizing that there are still so many helpers – so many caring people in this world.”
heidi@trianglephysician.com
Contributing Editors William Goodnight III, M.D., M.S.C.R. Amanda Kanaan Andrea Lukes, M.D., M.H.Sc., F.A.C.O.G.
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In her correspondence, my sister included suggestions for spending quality time with loved ones that began with turning off the TV.
Opinions expressed or facts supplied by its authors are not the responsibility of The Triangle Physician. The Triangle Physician makes no warrant to the accuracy or reliability of this information.
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Cover
Carolina Partners in Mental HealthCare
Leading the Way with Cutting-Edge Care and New TMS Therapy for Depression By Rory Cullen
Depressive disorders affect nearly 19 million Americans – some
Advancing Accuracy and Efficacy
9.5 percent of the adult population.
For Dr. Smith and his colleagues, it’s just another example of providing the highest degree of accuracy and efficacy to a field
No other mental disorder is responsible for a comparable degree
often perceived as nebulous and subjective, and delivering
of lost productivity and absenteeism, costing businesses an
treatment procedures that sometimes appear haphazard.
estimated $51 billion each year. The human costs are higher still: statistics suggest that as many as 10 percent of depressed patients
Patients at Carolina Partners in Mental HealthCare can expect ex-
eventually attempt or commit suicide.
tensive neurocognitive testing, performed on standardized rating scales, to reduce the guesswork involved, sometimes accompa-
Many patients never seek treatment, considering it a personal
nied by more exotic methods. “We can perform genetic testing to
weakness or not wishing to bear the stigma often associated with
determine (a patient’s) odds of responding to a particular treat-
the condition; others have little faith in the field of mental health
ment,” says Dr. Smith. “We give people less trial and error and
care – an attitude not helped by the relatively low effectiveness
more benefits.”
of many treatment options. It is not uncommon for a psychiatrist to prescribe a half-dozen different antidepressants before
“We provide data-driven, evidence-based care,” says Dr. Vaishnavi.
discovering one that works.
“We have a variety of methods to go deeply, to get the most objective diagnosis. Based on what we find, we have patients go
James Smith III, M.D., of Carolina Part-
down different paths, one of them being TMS.”
ners in Mental HealthCare explains how
James Smith III, M.D.
many patients are frustrated by the lack
Patients
of certitude. “When you go to the doctor
dedication. Founded by Yvonne Monroe,
with a sore throat, he swabs your throat
M.D., Carolina Partners opened its doors
and sends it to the lab. That tells him ex-
in 1994 with two small offices – one in
actly what drug to give you. For psychiat-
Chapel Hill and one in Henderson. Since
ric care, we simply don’t have that.”
then, the mental health practice has
seem
to
appreciate
their
grown to be the largest in the area, with When the opportunity for a better treatment option presented it-
Rohima Miah, M.D.
13 offices across the Triangle and beyond.
self, Dr. Smith was quick to investigate, eventually bringing NeuroStar transcranial magnetic stimulation (TMS) therapy to Caro-
Dr. Smith joined the clinic in 2005, coming in from nonprofit work
lina Partners. With the assistance of Sandeep Vaishnavi, M.D.,
with a plethora of ideas. He admits that the steep cost of the TMS
Ph.D., and Rohima Miah, M.D., the prac-
machine concerned some of his cohorts. “My partners were a
tice now delivers innovative treatment to
little nervous at first. But we all came together around this. We
depressive patients in the Triangle area.
wanted to be on the cutting edge.”
“I was blessed with Dr. Miah and Dr. Vaishnavi,” says Dr. Smith. “They’re both
New Therapy Improves Treatment of Major Depressive Disorder
very bright, very academic. They’re great
Transcranial magnetic stimulation is a noninvasive procedure
clinicians.”
that uses a charged coiled wire to project rapid magnetic pulses
Sandeep Vaishnavi, M.D.
6
The Triangle Physician
into the brain. The resulting magnetic
patients often must go through several
affected area.
different
field induces weak electrical currents
antidepressants,
sometimes
that depolarize or hyperpolarize neurons
The treatment consists of five sessions
over the course of a year or more, before
within the field. This assists or inhibits
a week for six weeks. Each session lasts
finding one they respond to – if they
these neurons in “firing” or generating
approximately 30 minutes, with the
find one at all. “The chance of getting
an
patient reclining comfortably in a chair
an antidepressant that works drops after
while the device operates. No sedatives or
each attempt,” says Dr. Miah. “After four,
anesthetics are required; patients remain
it’s less than 7 percent.”
action
potential
and
releasing
neurotransmitters. Since 1985, TMS has been used to study
alert throughout the procedure and are
the structure of the brain without resorting
free to drive afterwards. “You can do it on
“For a lot of people, (antidepressants are)
to the uncomfortable and sometimes
your lunch break,” says Dr. Vaishnavi.
a daily chore, a hassle,” says Dr. Vaishnavi. “And then there are the side effects.” The
dangerous practice of direct electrical Neurologists
Traditional modern psychiatric treatments
infamous side effects of antidepressants
began exploring the use of TMS for the
for MDD center on a bevy of brand-name
are sometimes worse than the perceived
treatment of a variety of disorders in the
drugs, particularly selective serotonin
benefits, causing patients to stop taking
1990s and have since conducted hundreds
reuptake inhibitors (SSRIs) or monoamine
them entirely.
of trials. Following thorough study, recent
oxidase inhibitors (MAOIs) that alter the
approval of TMS to treat major depressive
neurochemistry of the brain over time
For patients who have found these
disorder (MDD) by the United States Food
to ameliorate depressive symptoms. But
treatment options unsatisfactory, TMS
and Drug Administration has opened a
the efficacy of any single drug is low, and
stands in sharp contrast. “You could be
stimulation
of
neurons.
tremendous opportunity. “This is a whole new way of treating neuropsychiatric disorders,” says Dr. Vaishnavi. “It’s very exciting new technology. Until now, we didn’t really have a good outpatient tool that could directly affect brain circuitry in modulating moods.” Although the details of the underlying neurobiology are still unclear, it is known that the prefrontal cortex – an area associated with mood – is underactive in patients with MDD. The NeuroStar TMS device is capable of precisely targeting neurons in this region, stimulating activity and the release of neurotransmitters. “Over time, that part of the brain becomes more metabolically active,” says Dr. Vaishnavi. “We see more bloodflow to that area. It acts as a brake on the emotional brain, leading to the relief of depressive symptoms.” TMS is indicated for patients who have already taken at least one antidepressant at the minimum effective dosage. As with magnetic resonance imaging scanners and other medical devices that project a magnetic field, patients must be able to remove any metal implants near the
Robyn Gaylor and Dr. Vaishnavi give us a closer look at the machine.
decemBER 2012
7
of impressive data and years of safe use. Still, many insurance carriers continue to evaluate the new treatment. Because some remain wary of the lack of longitudinal data and coverage is spotty, Carolina Partners has been working to raise awareness. “Clearly it’s still new,” says Dr. Smith. “Psychiatrists in general are used to talk therapy or medications, but we’re not used to procedures… This is a new deal. Right now, I want to work with insurance companies to make TMS available to everybody. The efficacy is proven. It is The Carolina Partners TMS team with Drs. Smith, Vaishnavi and Miah, and Liz Griffen (left) and Robyn Gaylor (right).
safe. I’d love to see Blue Cross cover this treatment, so we can help folks stay functional.”
on your fourth or fifth antidepressant.
stimulation applied to their brains, TMS
The likelihood of you getting better is 25
does not induce the notorious side effects
Developments elsewhere in the nation
percent at best – at best,” says Dr. Smith.
of electroconvulsive therapy (ECT) –
have been encouraging. “In New England,
“If I get you in that chair, I’m giving you
memory loss and unpredictable cognitive
Medicare reimburses for TMS,” says Dr.
a 50 percent chance at improvement.”
dysfunction.
Smith. “I want to get it approved in North
Recent trials suggest the efficacy may be
Carolina as well. Lots of seniors are
even greater, with results of 53 percent
Maintenance sessions of TMS remain
to 58 percent appearing in published
effective for patients who relapse, a
reports. “We’re very excited to offer this to
common occurrence in MDD. “When
In the interim, Carolina Partners Mental
people who’ve been down that path talk
symptoms return – and they return in
Healthcare offers a variety of payment
therapy and medications) and gotten no
two-thirds of patients – over 85 percent of
plans to assist patients in shouldering the
benefit,” adds Dr. Miah.
patients respond to TMS,” says Dr. Miah.
financial burden. Dr. Miah encourages
TMS presents another major advantage
Hope for the Future
over antidepressants. “Mostly when I
Psychiatrists
are
the cost of depression in your life… I had a
talk about drugs, I talk about a balance
cautiously optimistic that TMS may be
patient who was out of work for two years
between efficacy and side effects. Here,
useful in treating additional disorders as
due to depression. That’s a huge cost.”
there are virtually no side effects,” says
well. “That’s the beauty of it,” says Dr.
Dr. Miah. “Maybe a little bit of scalp
Vaishnavi. “We know the neural circuitry
Some sufferers of MDD seem to agree; Dr.
pain, headaches or toothaches, but
for a lot of these other disease states. It’s
Miah and Dr. Vaishnavi have consulted
these usually resolve with time or with
not too big a leap to start treating that
with several patients who are set to begin
medication.” Many patients report the
particular circuit. We can increase the
treatment soon.
discomfort dissipating within the first
efficacy of that brain region or inhibit it.”
struggling with depression.”
patients to carefully weigh the benefits and
neurologists
against the expense. “You have to look at
week of treatment.
But Dr. Smith remains, perhaps, the most Tourette’s syndrome, anxiety disorders,
enthusiastic of all. “We’re going to be able
“If you’re on medication, and it’s working,
bipolar disorder, Parkinson’s disease
to give Wake County truly cutting-edge
great,” continues Dr. Miah. “But if you
and numerous others are being studied.
care. I take a lot of pride in that.”
have
“I think (treatment of) MDD is just the
intolerable
side
effects
(from
antidepressants), this is a viable option.”
beginning,” says Dr. Vaishnavi.
While many patients may be nervous
TMS has met a warm welcome in the
call (919) 929-9610 or
at
the
psychiatric community, buoyed by reams
toll-free (877) 876- 3783.
8
The Triangle Physician
For more information, visit www.carolinapartners.com or
prospect
of
electromagnetic
Weight Management
A New Way to
Conquer Weight Gain By Andrea Lukes, M.D., M.H.Sc., F.A.C.O.G.
Important developments in losing weight
ties, including diabetes or prediabetes,
include the newly launched drug that com-
hypertension, dyslipidemia and abdominal
bines phentermine and extended-release
obesity. Specifics of the trial show that two
topiramate.
different doses of phentermine plus topira-
After earning her bachelor’s degree in religion from Duke University (1988), Dr. Andrea Lukes pursued a combined medical degree and master’s degree in statistics from Duke (1994). Then, she completed her ob/gyn residency at the University of North Carolina (1998). During her 10 years on faculty at Duke University, she cofounded and served as the director of gynecology for the Women’s Hemostasis and Thrombosis Clinic. She left her academic position (2007) to begin Carolina Women’s Research and Wellness Center, and to become founder and chair of the Ob/Gyn Alliance. She and partner Amy Stanfield, M.D., F.A.C.O.G., head Women’s Wellness Clinic, the private practice associated with Carolina Women’s Research and Wellness Clinic. Women’s Wellness Clinic welcomes referrals for management of heavy menstrual bleeding. Call (919) 251-9223 or visit www.cwrwc.com.
mate were compared in overweight/obese While phentermine and topiramate have
subjects (with two or more comorbidities)
been available for many years, their com-
as an adjunct to diet and lifestyle changes.
bined use in the drug Qsymia, marketed by Vivus Inc., to treat obesity is worthy of
Of the 2,487 patients in the study, 994 were
attention.
assigned to the placebo (979 analyzed), 498 to 7.5 milligrams phentermine plus 46
More than one-third of adults in the United
milligrams topiramate (488 analyzed), and
States (35.7 percent) are obese (www.cdc.
995 to 15.0 milligrams phentermine plus 92
gov/obesity/data/adult.html). The Centers
milligrams topiramate (981 analyzed).
for Disease Control and Prevention view obesity as common, serious and costly.
At the lower dose, the mean weight loss
Obesity-related conditions include heart
was 8.1 kg or 17.8 pounds. At the higher
disease, stroke, type 2 diabetes and certain
dose the mean weight loss was 10.2 kg
types of cancer. Per the CDC, the medical
or 22.4 pounds. These were both statisti-
costs associated with obesity were estimat-
cally higher than the placebo group, which
ed at $147 billion in 2008.
had a weight loss of 1.4 kg or 3.1 pounds. Weight loss of 10 percent or greater at one
The indication for Qsymia is as an adjunct
year was seen in: 7 percent of the placebo
www.sparkspeople.com, www.nutrihand.
treatment to a reduced calorie diet and in-
group, 37 percent of the low-dose group
com and www.mypyramid.com. I recom-
creased physical activity for chronic weight
and 48 percent of the high-dose group.
mend the “Q and Me,” weight-loss support program available on the Qsymia website
management in adults. They should have an initial body mass index of 30 or greater
at hwww.qsymia.com.
In addition to medications though, there is
or 27 or greater with the presence of at
basic information that should be provided
least one weight-related comorbidity, such
to help with weight loss:
•E xercise is essential for weight loss and weight control. •B e mindful of food quantity and quality.
as hypertension, type 2 diabetes or high
•T o lose one pound in a week, one must
cholesterol. Our experience at Women’s
have a deficit of 3,500 total calories in
•D o not multitask when you are eating.
Wellness Clinic is that it can work well, and
a week (500 calories per day for seven
•C hew foods well and eat slowly.
days).
•G ive your pantry and refrigerator/freezer
patients are excited and motivated to try it.
a makeover by eliminating foods that
•A void slowing metabolism down by conA study published in The Lancet in 2011
suming no fewer than 1,200 calories per
demonstrated the effects of this combined
day.
tempt you. •D o not eat late at night.
drug (low-dose phentermine, plus topira-
•E at less, but more often to boost metabo-
mate) on weight and associated comor-
lism. Consume five to six small meals
bidities in overweight and obese adults
during the day, beginning with breakfast
(CONQUER)1.
within 45 minutes of walking. • Keep a food journal. An online version that
The adults evaluated had BMIs between
keeps calorie count is ideal, such as www.
27-45 kg/m2 and two or more comorbidi-
thedailyplate.com, www.calorieking.com,
Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults CONQUER: A randomized, placebo-controlled, phase 3 study. Lancet 2011; DOI:10.1016/S01406736(11)60505-5. Available at www.thelancet.com. 1
decemBER 2012
9
Fetal Surgery
In-utero Surgery for Spina Bifida to Improve Postnatal Outcome By William Goodnight, M.D., M.S.C.R.
Spina bifida affects one in 2,858 live
neonate. In 2003, the Management
births in the United State, with an an-
of Myelomenigocele Study (MOMS)
nual estimated number of 1,460 cases
was conducted under the National
(1). Spina bifida results from failure
Institute of Child Health & Human
of closure of the neural tube between
Development (NICHD) with the re-
26 and 53 days of pregnancy, result-
sults reported in 2011 (2). In this trial,
ing in failure of formation of the ver-
women with fetus with MMC and Chi-
tebral bodies (spina bifida occulta), herniation of the meninges through an
Fig 1
ari malformation were randomized to in-utero repair (92) between 19-26
opening in the skin (meningocele) or
weeks gestational age or post-natal
herniation of meninges and the spinal
repair (91).
cord and/or nerve roots through the de-
Ventriculoperitoneal (VP) shunting of
fect (myelomingocele, figure 1).
the cerebrospinal fluid is used to manage
This trial demonstrated that in-utero repair
hydrocephalus and is required in 75-85
was associated with a lower incidence of
Myelomingocele (MCC), the most signifi-
percent of cases. Approximately 50-75 per-
VP shunt placement or death in the first
cant and frequent spina bifida lesion, re-
cent of patients require a shunt revision in
year of life among those with in-utero
sults in two major complications: injury to
the first two years of life.
repair compared to post-natal closure of the spina bifida (68 percent vs. 98 percent
the peripheral nerve roots and potential development of a Chiari II malformation,
Spina bifida also is associated with an
p<0.001). The MOMS trial suggested a 52
or herniation of the brainstem and medul-
increased risk of cognitive disability. Fac-
percent reduction in the risk of VP shunt
la through the foramen magnum.
tors associated with intellectual disability
placement in the first year of life with in-
include higher level lesions, Chiari malfor-
utero surgery.
Nerve-root injury in MMC is associated
mation and repeat central nervous system
with sensory deficits and motor paralysis
(CNS) complications, such as CNS infec-
In addition, this trial demonstrated bet-
at and below the site of the lesion, includ-
tion and VP shunt failure/revision. Thus
ter motor and mental developmental
ing neurogenic bowel and bladder. Most
interventions to reduce the risk of CNS
scores with in-utero repair. Fetal surgery
lesions are located in the mid-lumbar
complications may improve the long-term
does carry risk to the pregnancy, with the
spine, and the exact vertebral level of in-
outcomes in spina bifida patients.
most common being preterm premature rupture of membranes (PPROM) and pre-
jury determines the lifetime ability for independent ambulation. Thoracic lesions
Prenatal Management
term birth (PTB). In the MOMS trial, all
carry low likelihood of independent am-
of Spina Bifida
pregnancies were delivered by 37 weeks
bulate with low lumbar lesions resulting
Traditional care for MMC includes contin-
by cesarean and the in-utero repair was
in community ambulation as young adults
ued fetal evaluation during pregnancy, and
noted to have higher rates of PPROM (46
in up to 95 percent of cases.
most cases are delivered by cesarean deliv-
percent vs. 8 percent), earlier gestational
ery prior to the onset of labor. The MMC is
age at birth (34.1 vs. 37.3 weeks gesta-
then repaired on the first day of life.
tional age) and lower mean birthweights
Chiari II malformation occurs in 80-90
(2,383 grams vs. 3,039 grams). Despite
percent of MMC and is complicated by hydrocephalus in more than 90 percent
Animal data and early human cases be-
these potential risks, the MOMS trial con-
of cases. The presence of brainstem her-
tween 1997-2001 suggested that in-utero
cluded that in-utero repair appears benefi-
niation and hydrocephalus can result in
repair of the MMC could result in a reduc-
cial in reduced need for VP shunting and
brain injury and central apnea, a common
tion in the incidence of hydrocephalus
improved motor and mental development
cause of death in spina bifida.
and reduced need for VP shunting in the
outcomes at 30 months of age.
10
The Triangle Physician
Fetal Surgery for Myelomingocele The University of North Carolina was one of the original programs prior to the MOMS trial to offer in-utero repair, but like other centers, it agreed to a hiatus on performing the procedure outside of the trial until it was completed. With successful completion of the MOMS trial, UNC has again been performing in-utero surgery for MMC for appropriate candidates; the only center in southeastern United States. The UNC Fetal Program is part of the UNC Center for Maternal and Infant Health (CMIH), a multidisciplinary center to care for these complicated
Three-dimensional ultrasound of thoracic open spina bifida.
pregnancies. The fetal program includes: • Maternal-fetal medicine (MFM) specialists and genetic counselors, who help diagnose spina bifida; • Patient care coordinator, who helps the family navigate their care during the pregnancy and in the first few years after delivery; • Pediatric neurosurgical specialists; • Obstetrical anesthesiology; • Physical medicine and rehabilitation specialists in the spina bifida clinic, who provide lifelong care in spina bifida. Candidates for in-utero fetal repair of MMC include: • Lesion between T1 and S1 with a Chiari malformation and no other
Ultrasound image of MMC.
major fetal anomaly; • No significant maternal risk factors for preterm birth or prior extensive uterine surgery (a prior cesarean is not an exclusion); • Gestational age at time of repair of 20-25 weeks. Evaluation for in-utero repair includes detailed fetal ultrasound (figure 2) and usually fetal magnetic resonance imaging to determine the level of the lesion and exclude other anomalies, amniocentesis for karyotype evaluation and maternal physical examination to determine the presence of any factors that may make in-utero repair more risky than postnatal repair.
Cary Endocrine & Diabetes Center, P.A.
Uterine incision.
CEDC provides diagnosis and treatment for patients with hormonal and metabolic disorders including: diabetes, lipid disorders, PCOS, thyroid disorders, osteoporosis and other bone disorders, pituitary disorders, adrenal disorders, and sex hormone disorders.
Celebrating our first year in Cary!
Sung-Eun Yoo, MD
Endocrinologist Diplomat, American Board of Endocrinology, Diabetes and Metabolism Diplomat, American Board of Internal Medicine Endocrine Certification in Neck Ultrasound (ECNU) Certification in the International Society for Clinical Densitometry (ISCD)
On-Site Services: • Thyroid, parathyroid and neck ultrasound • Ultrasound guided FNA • DEXA bone density scans and interpretation • Osteoporosis therapy • Comprehensive diabetes management including diabetes education, insulin pump therapy, and continuous glucose monitoring • LabCorp in-house Introducing Jeanne Hutson, NP-C Board Certified in Advanced Diabetes Management
Cary Endocrine & Diabetes Center, P.A. • 103 Parkway Office Court, Suite 202 • Cary, NC 27518 • 919-378-2332 • www.caryendocrine.com
decemBER 2012
11
Fetal MMC prior to repair.
to six days following the surgery and
preterm delivery, as well as time out from
receives medication to reduce the
work and away from family that could be
risk of preterm labor (PTL). After
disruptive to the motherâ&#x20AC;&#x2122;s daily life. Based
discharge, reduced maternal physi-
on the current evidence, in-utero repair
cal activity and weekly follow up is
of spina bifida in appropriate cases may
planned. Delivery is then performed
provide improvement in the first few years
by cesarean delivery at 37 weeks, ide-
of life and holds promise for reducing the
ally prior to the onset of labor.
morbidity of MMC in selected patients.
In-utero surgery holds the potential
For consultation regarding in-utero fetal
for reduction in morbidity from com-
surgery for spina bifida, as well as care
plications associated with spina bifi-
and diagnosis for other fetal complica-
da, but does carry potential risks and
tions and congenital anomalies, call UNC
long-term maternal consequences.
MFM at (919) 843-6094 or the Center for
Based on the size and location of the
Maternal and Infant Health Care coordina-
uterine incision, there is an increased
tor at (919) 843-4428.
risk of uterine rupture with labor, and a cesarean delivery is performed at 37 weeks with the current and all fuFetal MMC closed.
ture pregnancies.
After this evaluation, if in-utero surgery is
The risk of PPROM and PTL/PTB may re-
selected, the repair is performed close to
quire frequent maternal hospitalization,
23-25 weeks gestational age. During the
ongoing medication use and possible
References 1 Parker SE, et al. Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004-2006. Birth Defects Res A Clin Mol Teratol. 2010 Dec;88 (12): 1008-16. 2 Adzick S, et al. A Randomized Trial of Prenatal versus Postnatal Repair of Myelomeningocele. N Engl J Med 2011;364:993-1004.
procedure, which may last two hours, the mother undergoes general anesthesia, and a skin incision similar to a cesarean delivery is performed. A hemostatic incision is made in the uterus, while medications are given to maintain uterine relaxation, with care being taken to not disturb the placenta (figure 3). Oxygen and anesthesia continue to pass to the fetus via the placenta and umbilical cord. The MFM physician performs the uterine incision and fetal positioning and monitors the fetal heart with ultrasound during the procedure. The fetus is then positioned to expose the MMC at the uterine incision and
Partnering with patients and providers for a healthier community.
the neurosurgeon closes the defect. The neurosurgical procedure is very similar to that done on neonates postnatally. The meningocele sac is dissected away from normal skin on the back and the neural
Meet Dylan...
Lost: 135 lbs Found: A New Lifestyle
placode dissected free to drop into the spinal canal. The dura is then sutured to recreate a tube over the spinal cord and the fetal skin mobilized to close over the dura. Amniotic fluid is then replaced, and the uterine incision is closed. The mother is usually in the hospital for three
12
The Triangle Physician
Joseph C. Moran, MD, FASMBS 2801 Blue Ridge Road, Suite 101 Raleigh, NC 27607
P: 919.781.0815 F: 919.781.0816
www.alasurgery.com
Practice Management
5 Reasons
Why Online Marketing Should Be Part of Your Marketing Plan in 2013 By Amanda Kanaan
The month of December is often a time of
range of demographics. The fact that
reflection, planning, and goal-setting for the
you cater to a geriatric population is no
upcoming year. For most practices, as with
longer an excuse. The 70-75 year-old age
any small business, these goals usually in-
group is the fastest growing demograph-
clude increasing the amount business from
ic of Internet users (2009 study by Pew
the year before. When discussing marketing
Internet & American Life Project).
strategy every medical practice, regardless
5. Targeted Approach: If you are a plastic
of size or specialty, should consider invest-
surgeon who wants to do more mommy
ing in online marketing in 2013. Here are five
makeovers, for example, you can easily
reasons why…
use online marketing to target specific
1. Cost-Effective: The cost is lower than
keywords and demographics related to
traditional media such as TV or radio and
this service. It’s a great way to establish a
can often have a greater ROI due to the
niche or at least bill more of a particular
long lasting effects.
service.
2. Increasing Demand: We are in the
Amanda Kanaan is the president and founder of WhiteCoat Designs, a North Carolinabased marketing agency catering specifically to physicians. WhiteCoat Designs offers doctors affordable marketing solutions to help them grow their practices. Services include website design, search engine optimization (SEO), social media management, online reputation monitoring, brochure and collateral design, branding makeovers and physician liaison services to build patient referrals. Ms. Kanaan can be reached at amanda@whitecoat-designs. com or (919) 714-9885. To learn more, visit www.whitecoat-designs.com.
midst of an “e-patient” revolution (pa-
Whether you invest in search engine op-
tients whose number one source of
timization (SEO), pay-per-click (PPC) ad-
health information is the Internet). As
vertising, or social media, the first step in
more and more health care organiza-
an effective online marketing strategy is a
tions realize this, the market space will
good website. The goal of online marketing
become increasingly competitive.
is to bring people to your website; the goal
on to your competitor’s site. Therefore, on-
3. Highly Trackable: Unlike some market-
of your website is to bring people to your
line marketing won’t be nearly as successful
ing strategies, the results of online mar-
practice. On average, your website has seven
without a great website and a great website
keting are highly trackable. Most Inter-
seconds to make an impression on a patient.
won’t be nearly as successful without online
net marketing agencies provide monthly
Otherwise, it’s back to the search engine and
marketing.
reports showing how your
engine
One of the great qualities
rankings are increasing
search
of online marketing is that
and the direct correla-
it’s an even playing field.
tion to your number
Whether you are a solo fam-
of visitors, as well as
ily practitioner or a 10 physi-
the number of visitors
cian cardiology practice, you
you are converting (i.e.
each have the opportunity to
number of online ap-
compete online. So as you
pointment
enter into budget discussions
requests,
etc.).
this month and consider your
4. Wide Appeal: Online
goals for next year, consider
marketing is a highly
online marketing as a cost-
effective marketing tool
effective approach to growing
that caters to a wide
your practice in 2013.
decemBER 2012
13
February 2nd at Beaver Pond Sporting Club Sponsored by In 2010 a group from the High Point area discussed the difficulties experienced by young men and women returning from Operation Enduring Freedom, our current operations in Iraq and Afghanistan. Our Soldiers, Marines, Sailors and Airmen are engaged in the longest war in the history of the United States and the size of our fighting force is the smallest it has been in recent history. As a result, our servicemen and women were experiencing multiple deployments; some as many as ten with three or four deployments during this time period being common. Many of these who’ve served multiple deployments are National Guard and Reserve, and not even full time soldiers. Thousands of first Little League games, dance recitals, births, and other milestone occasions in their lives and the lives of their families have been missed. As citizens who appreciate the sacrifices and efforts of these brave young men and women, the group formed Enduring Gratitude www.enduringgratitude.org, a 501c3 Charitable Non-profit with the express purpose of providing these, who have volunteered, served, and sacrificed with a memorable experience in the outdoors as an expression of our gratitude. We have recently changed our eligibility to include all those who have served in conflicts and put their lives on the line for our freedom. Unlike many similar organizations, there are no paid employees of Enduring Gratitude. Since our inception, we’ve hosted multiple events including bird hunts, deer hunts, turkey hunts, and waterfowl hunts for soldiers across our state. Some events are small with only a half dozen or so participants and some are quite large with almost 60 veterans at the last Enduring Gratitude Pheasant Tower shoot at Beaver Pond Sporting Club. To make this happen, we need others like us who are grateful for the sacrifice of these men and women. doing this requires money, and volunteers and we’re counting on Americans like us to help make this happen. To make this one event happen, we need $18,000 in donations and about 50 volunteers. Please look into Enduring Gratitude and consider getting involved in thanking this new generation of heroes for their sacrifice. enduringgratitude.org Media Coverage: Last year, we were covered on WXII TV, Fox 8 TV, News 14, and The Wolf radio, as well as in newspapers and other publications. Proposed Schedule: Details on the February 2nd Enduring Gratitude Event at Beaver Pond www.BeaverPondNC.com Snow Camp, NC 8:00 a.m. Veterans arrive for Coffee, Danish and registration. Participants will be split into two groups. Those with wing shooting experience can go to the fields for the morning pheasant hunt. The second group with less experienced shooters will go to the Five Stand for sporting clays and a little shotgun instruction. Veterans who don’t wish to hunt and/or shoot may fish the lake at Beaver Pond. All events are optional. 8:30 a.m. Group one heads to the fields and group two to the Five Stand and other events. 11:30 a.m. Participants will rejoin in the lodge at Beaver Pond for a pig picking and speech by General Tom Metz. 1:00 p.m. Second group will head for the pheasant fields while the second group will be squadded for Five Stand and avail themselves of the other shooting games. During the hunts, dog handlers and their dogs will retrieve birds and volunteers will round up the birds to be taken back to the cleaning shed where more volunteers will clean and package them for the veterans to take home to their families. On completion of the second hunt, everyone will reconvene in the lodge for awards and door prizes.
Sponsorship Levels: To make all this happen, Enduring Gratitude needs sponsors. If desired, sponsors have priority for volunteer positions. Sponsor an individual soldier.................................. $300
Rimfire Pistol Gallery with signage.......................... $1000
Sporting Clays with signage.................................... $1000
Centerfire Pistol Plate Event with signage................ $1000
Rimfire Rifle Gallery with signage............................ $1000
Fishing Event with signage...................................... $1000
Name: __________________________________________
Email address:_____________________________________
Company: ________________________________________
Business Phone #___________________________________
Address: _________________________________________
Cell#_____________________________________________
City: ________________________ State:____ Zip: _______ We accept Check, Visa, MC, AMEX, Discover, and PayPal
Amount: _____________Check ## or CC#_______________
Please mail back to: Enduring Gratitude c/o Ray Shufelt PO Box 5545 High Point, NC 27262
Duke News
Hospital Names New President Gan-
in several positions of increasing responsi-
A registered nurse and nurse practitioner,
notta, D.H.A., M.B.A., N.P.,
bility during a 12-year career at WakeMed’s
Dr. Gannotta received his undergraduate
F.A.C.H.E., has been named
Raleigh campus, including senior vice
degree from Florida International Univer-
president of Duke Raleigh
president and administrator, vice president
sity, a master of business administration
Hospital, effective Jan. 1.
of operations and patient care, chief nurs-
from Campbell University and doctorate in
ing officer and executive director of the
health care administration from the Medi-
WakeMed Heart Center.
cal University of South Carolina. He is in-
Richard
J.
“Rick”
Dr. Gannotta has served as the chief oper-
volved in a variety of professional activities
ating officer of Duke Raleigh since 2006, overseeing the hospital’s operations, nurs-
In addition to his leadership role at Duke
and holds several honors, including fellow
ing and clinical activities and financial
Raleigh, Dr. Gannotta teaches at the Duke
of the American College of Healthcare Ex-
outcomes. He succeeds Doug Vinsel, who
University School of Nursing, serving as a
ecutives, and fellow and past board mem-
announced his retirement as president of
faculty member for the health care leader-
ber of the Johnson & Johnson-Wharton
Duke Raleigh Hospital in August.
ship track. His research interests include
Fellows Program in Management for Nurse
patient safety, new models of care delivery
Executives.
Prior to joining Duke, Dr. Gannotta served
and health care policy and reform.
Duke Research News
Aerobic Exercise is Better for Weight and Fat Loss Than Resistance Training Aerobic training is the best mode of ex-
“Given that approximately two-thirds of
randomly assigned to one of three exercise
ercise for burning fat, according to Duke
adults in the United States are overweight
training groups: resistance training (three
Medicine researchers who compared aero-
due to excess body fat, we want to offer
days per week of weight lifting, three sets
bic training, resistance training and a com-
clear, evidence-based exercise recom-
per day, 8-12 repetitions per set), aero-
bination of the two.
mendations that will truly help people lose
bic training (approximately 12 miles per
weight and body fat,” said Leslie H. Willis,
week), or aerobic plus resistance training
The study, which appears Dec. 15, in the
M.S., an exercise physiologist at Duke Med-
(three days a week, three sets per day, 8-12
Journal of Applied Physiology, is the larg-
icine and the study’s lead author.
repetitions per set for resistance training, plus approximately 12 miles per week of
est randomized trial to analyze changes in body composition from the three modes
Researchers enrolled 234 overweight or
of exercise in overweight or obese adults
obese adults in the study. Participants were
aerobic exercise).
without diabetes. Aerobic exercise – including walking, running and swimming – has been proven to be an effective way to lose weight. However, recent guidelines have suggested that resistance training, which includes weight lifting to build and maintain muscle mass, may also help with weight loss by increasing a person’s resting metabolic rate. Research has demonstrated health benefits for resistance training, such as improving glucose control, but studies on the effects of resistance training on fat mass have been inconclusive.
The Triangle Physician 2013 Editorial Calendar January Glaucoma Wound Management Accounting
May Arthritis Women’s Health Medical Billing
September Atrial Fibrillation Urology Web Design
February Asthma and Allergies Heart Disease Consulting for your Practice
June Men’s Health Vascular Diseases Medical Collections
October Cancer in Women COPD - Lung Health Medical Software - EMR
March Nutrition Sleep Disorders Legal
July Imaging Technologies Psoriasis Medical Insurance
November Alzheimer’s Disease Diabetes Financial Planning
April Autism Irritable Bowel Syndrome IT Services
August Orthopedics Gastroenterology Medical Real Estate
December Pain Management Spine Disorders Practice Management
decemBER 2012
15
Duke Research News The exercise sessions were supervised
Duke researchers added that exercise
gist and study co-author. “It’s not that resis-
in order to accurately measure adher-
recommendations are age specific. For
tance training isn’t good for you; it’s just not
ence among participants. Data from 119
older adults experiencing muscle atrophy,
very good at burning fat.”
people who completed the study and had
studies have found resistance training to
complete body composition data were
be beneficial. However, younger, healthy
In addition to Ms. Willis and Mr. Slentz,
analyzed to determine the effectiveness of
adults or those looking to lose weight
Duke study authors include Lori A. Bate-
each exercise regimen.
would see better results doing aerobic
man, Lucy W. Piner, Connie W. Bales and
training.
William E. Kraus. East Carolina University study authors include A. Tamlyn Shields
The groups assigned to aerobic training
and Joseph A. Houmard.
and aerobic plus resistance training lost
“Balancing time commitments against
more weight than those who did just re-
health benefits, our study suggests that
sistance training. The resistance training
aerobic exercise is the best option for re-
The study was funded with a grant from the
group actually gained weight due to an in-
ducing fat mass and body mass,” said Cris
National Heart, Lung, and Blood Institute,
crease in lean body mass.
A. Slentz, Ph.D., a Duke exercise physiolo-
National Institutes of Health
Aerobic exercise was also a more efficient method of exercise for losing body fat. The aerobic exercise group spent an average of 133 minutes a week training and lost weight, while the resistance training group spent approximately 180 minutes exercising a week without shedding pounds. The combination exercise group, while requiring double the time commitment, provided a mixed result. The regimen helped participants lose weight and fat mass, but did not significantly reduce body mass nor fat mass over aerobic training alone. This group did notice the largest decrease in waist circumference, which may be attributed to the amount of time participants spent exercising. Resting metabolic rate, which determines how many calories are burned while at rest, was not directly measured in this study. While theories suggest that resistance training can improve resting metabolic rates and therefore aid in weight loss, in this study resistance training did not significantly decrease fat mass nor body weight irrespective of any change in resting metabolic rate that might have occurred. “No one type of exercise will be best for every health benefit,” Ms. Willis said. “However, it might be time to reconsider the conventional wisdom that resistance training alone can induce changes in body mass or fat mass due to an increase in metabolism, as our study found no change.”
16
The Triangle Physician
Womens Wellness half vertical.indd 1
12/21/2009 4:29:23 PM
Duke Research News
Fragile X Protein is Linked to Nearly 100 Genes Involved in Autism Doctors have known for many years that
cases, none of the FMRP protein. As a re-
the subtle ways that genes get turned on
patients with fragile X syndrome, the most
sult, additional proteins it would normally
and off.”
common form of inherited intellectual dis-
regulate are made in the wrong place and
ability, are often also diagnosed with au-
at the wrong time. Until now, little was
Physicians who work with fragile X patients
tism. But little has been known about how
known about how this process worked in
know that each patient’s abilities and chal-
the two diagnoses are related.
people with the autism.
lenges are unique. Some individuals have
Now a collaborative research effort at Duke
Using a combination of laboratory experi-
University Medical Center and Rockefeller
ments and advanced bioinformatics, the
abilities. Approximately 2 percent to 6 per-
University has pinpointed the precise ge-
research team, led by Thomas Tuschl,
cent of children with autism are also diag-
netic footprint that links the two. The find-
Ph.D., a Howard Hughes Medical Institute
nosed with fragile X and about one-third of
ings, published online in the journal Na-
investigator at Rockefeller University, and
fragile X patients also meet the criteria for
ture on Dec. 12, point the way toward new
Uwe Ohler, Ph.D., an associate professor in
autism.
genetic testing that could more precisely
biostatistics and bioinformatics at the Duke
diagnose and categorize the spectrum of
Institute for Genome Sciences & Policy,
The new discovery should now enable re-
autism-related disorders.
identified both the genetic flags that FMRP
searchers to examine the common molecu-
is looking for and the genes it targets.
lar pathways leading to all forms of autism.
almost no disability, while others have more severe physical and intellectual dis-
Identification of those pathways could also
Fragile X syndrome is the most well under-
The researchers discovered
lead to more targeted treatments for both
stood single-gene cause
that FMRP directly controls
fragile X and autism.
of autism. It results from
at least 93 genes that have
defects on a small part
been independently linked to
“We can now look for changes in the FMRP
of the genetic code for a
autism, as well as Angelman,
binding sites of genes to identify potential
protein that researchers
Prader-Willi, Rett and other
new genetic links to autism-spectrum dis-
have dubbed the “frag-
neurologic syndromes that
orders,” said Neelanjan Mukherjee, a Duke
ile X mental retardation
have overlapping features with
post-doctoral scientist who contributed to
protein,” or FMRP.
autism.
the research.
Normally, FMRP plays
Additional
using
In addition to Drs. Ohler and Tuschl and
an important role in
a mouse model of fragile X
Mukherjee, study authors include Manuel
controlling production
syndrome revealed that the
Ascano Jr., Pradeep Bandaru, Jason B. Mill-
of other proteins in the
animals had abnormal protein
er, Jeff Nusbaum, David L. Corcoran, Chris-
brain and other organs.
production not only in the
tine Langlois, Mathias Munschauer, Scott
It does this by looking
brain but also in the ovary.
Dewell, Markus Hafner and Zev Williams.
for specific genetic pat-
The findings confirmed that
terns located on the
the absence of FMRP protein
The study was funded with grants from the
causes ovarian insufficiency,
National Institutes of Health (UL1RR024143,
which is common among
R01MH080442), the Howard Hughes Medi-
messages encoding proteins. When it locates
Fragile X Chromosome
these genetic flags, it attaches to them and,
research
women affected by fragile X syndrome.
cal Institute, Simons Foundation Autism Research Initiative, and the National Science
along with other signals, controls where “We now know not only which genes are
Foundation. The research team recently
linked to FMRP, but we can locate exactly
received an NIH transformative research
In fragile X syndrome, this process breaks
where they interact,” said Dr. Ohler. “Down
award (R01GM104962) that will enable the
down because a defect in the gene causes
the road, this finding could lead to more
team to continue its investigation.
the body to produce too little, or in some
detailed genetic tests that take into account
and when protein is made.
decemBER 2012
17
UNC Research News
Gene Therapy Cocktail Shows Promise for Children with Fatal Brain Disease Results of a clinical trial that began in 2001
Dr. Samulski arrived at UNC in 1993 to es-
with the replacement ASPA gene. About
show how a gene therapy cocktail con-
tablish the UNC Gene Therapy Center and
900 billion genomic particles of replace-
veyed into the brain by a molecular spe-
has long pioneered methodologies for us-
ment gene held by the AAV vector – rough-
cial-delivery vehicle may help extend the
ing viruses to deliver genes effectively and
ly the size of a quarter – were pumped into
lives of children with Canavan disease, a
safely to various targets in the body, includ-
each of the six catheter sites. The catheters
rare and fatal neurodegenerative disorder.
ing the brain, lungs, liver, heart and mus-
were then removed.
cle. As a graduate student at the University A report of the trial appears in the Dec. 19
of Florida in the early 1980s, his thesis proj-
Following the treatments, the patients went
online edition of the journal Science Trans-
ect on understanding and developing AAV
home with their families and were tracked
lational Medicine.
as a vector for delivering therapeutic genes
with behavioral tasks and brain imaging
helped launch this new field of molecular
studies. The investigators found that the
medicine.
gene therapy was safe and has led to a
This form of gene therapy was created
decrease in NAA in the brain and seizure
and developed at the University of North Carolina School of Medicine. The work was
This work eventually led to development of
frequency, as well as “clinical stabilization.”
spearheaded by R. Jude Samulski, Ph.D., a
AAV type 2, which has been used for gene
The greatest improvements were observed
study senior author, professor of pharma-
therapy vector trials in cystic fibrosis, he-
in the youngest patients who were treated
cology and director of UNC’s Gene Therapy
mophilia, Parkinson’s diseases and retinal
before age two. There also were improve-
Center. The treatment uses a virus (adeno-
disorders. The first gene therapy clinical
ments in attention, sleep and degree of
associated virus, or AAV) as a “viral vector,”
trial for muscular dystrophy in the U.S. was
movement when lying down and rolling.
meticulously tailored to enter the brain and
developed by Dr. Samulski and his first
safely switch good genes for bad.
graduate student, Xiao Xiao, Ph.D., profes-
“As the trial continued, the FDA let us go to
sor in the UNC Eshelman School of Phar-
younger and younger patients,” Dr. Samul-
macy, using AAV type 2.
ski said. “We were successful in being able
“This was the first AAV-based gene therapy
to treat a three-month-old infant who was
produced by a U.S. academic institution to be approved for neurological use by the
In this Canavan disease phase 1/2 safety
diagnosed in utero… and that child is alive
FDA (United States Food and Drug Admin-
study, 13 children were treated at the Cell
today and is the youngest person who has
istration),” Dr. Samulski said. “It’s also the
and Gene Therapy Center at the University
ever been treated with gene therapy.”
first vector produced by the university’s
of Medicine and Dentistry of New Jersey
Gene Therapy Center Vector Core facility
(UMDNJ) in Stratford, N.J. Principal inves-
The UNC scientist views the study as a defi-
to go into patients.”
tigator and first author of the study is Paola
nite success from a safety perspective. “The
Leone, Ph.D., associate professor of cell
genetic information put into the brains of
biology at UMDNJ.
individuals has not caused adverse effects,
Children with Canavan disease have muta-
toxicity or cancer. It also has great poten-
tions in the ASPA gene that normally codes for an enzyme that helps the brain degrade
The children were treated in 2001, 2003 and
tial efficacy for treating other degenerative
N-acetyl-aspartate (NAA). The unregulated
2005, corresponding to AAV vector produc-
neurological disorders, including Parkin-
buildup of NAA is toxic to the brain’s gray
tion runs. Their ages at the time of treatment
son’s and Alzheimer’s diseases.”
matter, the protective myelin sheath sur-
ranged from four months to 83 months. Co-authors along with Dr. Samulski at UNC
rounding nerve cells. Working with Dr. Samulski’s UNC lab col-
and Dr. Leone at UMDNJ were from six aca-
As the myelin deteriorates and neurons be-
leagues, Dr. Leone’s neurosurgical team
demic and clinical sites in the U.S. and New
come unable to communicate, the child’s
used magnetic resonance imaging to guide
Zealand: Children’s Hospital of Philadelphia;
head size increases (macrocephaly); move-
them to the proper location and depth in
New York University School of Medicine;
ment problems include inability to crawl, sei-
the lateral ventricle of the brain for insert-
Cooper Neurological Institute in Camden,
zures and vision impairment; and death often
ing six very thin catheters via small holes
New Jersey; the University of Minnesota
occurs within three years of age. Fewer than
drilled in the skull. The team then pumped
Medical School in Minneapolis; the Univer-
1,000 children in the U.S. have the disorder.
in a solution carrying the vector package
sity of Auckland in New Zealand; Ohio State
18
The Triangle Physician
UNC Research News University in Columbus, Ohio; and Asklepios
from the National Institute of Neurological
the National Endowment for Alzheimer’s
Biopharmaceuticals in Chapel Hill, N.C.
Disorders and Stroke, Canavan Research
Research.
Funds in support for the research came
Foundation, Jacob’s Cure Foundation and
Designer Drugs Effectively Hit Multiple Protein Targets At Once An international research collaboration
what is seen in ADHD: distractibility and
thus many never reach the market.
novelty seeking. “We created a compound
led by scientists at the University of North Carolina School of Medicine and the Uni-
Moreover, a drug that acts on a single tar-
that was predicted to prevent those recur-
versity of Dundee in the United Kingdom
geted protein may interact with many other
rent behaviors, and it worked quite well,”
has developed a way to efficiently and ef-
proteins. These undesired interactions fre-
Dr. Roth said.
fectively make designer drugs that hit mul-
quently cause toxicity and adverse effects. The researchers then tested the com-
tiple protein targets at once. “And so the realization has been that per-
pound in another mouse model where a
This accomplishment, described in the
haps one way forward is to make drugs
particular enzyme for a brain neuropeptide
Dec. 13 issue of the journal Nature, may
that hit collections of drug targets simulta-
is missing. Distractibility and novelty seek-
prove invaluable for developing drugs to
neously. This paper provides a way to do
ing also are behavioral features in these
treat many common human diseases, such
that,” Dr. Roth said.
animals. And the drug had the same effect in those mice.
as diabetes, high blood pressure, obesity, cancer, schizophrenia and bipolar disorder.
The new way involves automated drug design by computer that takes advantage of
The new drug design process includes en-
These disorders are called complex diseas-
large databases of drug-target interactions.
suring that compounds enter the brain by
es, because each has a number of genetic
The latter has been made public through
crossing the blood-brain barrier. These, too,
and non-genetic influences that determine
Dr. Roth’s lab at UNC and through other
were tested successfully in live animals.
susceptibility.
resources. According to Dr. Roth, pharmaceutical
“In terms of the genetics of schizophrenia,
Basically, the researchers – also co-led by
company chemists had suggested that the
we know there are likely hundreds of differ-
Andrew L. Hopkins, Ph.D., in the Division of
objective of a drug hitting multiple targets
ent genes that can influence the risk for dis-
Biological Chemistry and Drug Discovery,
simultaneously is impossible and unlikely
ease and, because of that, there’s likely no
College of Life Sciences, at the University of
to succeed. “Here we show how to effi-
single gene and no one drug target that will
Dundee – used the power of computational
ciently and effectively make designer drugs
be useful for treating it, like other common
chemistry to design drug compounds that
that can do that.”
complex diseases,” said study co-leader,
were then synthesized by chemists, tested
Brian L. Roth, M.D., Ph.D., Michael J. Hook-
in experimental assays and validated in
Along with Dr. Roth, the study’s 21 co-
er distinguished professor of pharmacol-
mouse models of human disease.
authors include the following from UNC:
ogy in the UNC School of Medicine, profes-
Vincent Setola, Xi-Ping Huang and Maria
sor in the Division of Chemical Biology and
The study team experimentally tested 800
F. Sassano. Other co-authors are from the
Medicinal Chemistry in the UNC Eshelman
drug-target predictions of the computation-
University of Dundee, Dundee, U.K.; Duke
School of Pharmacy and director of the Na-
ally designed compounds; of these, 75 per-
University Medical School, Durham; Clini-
tional Institute of Mental Health Psychoac-
cent were confirmed in test tube (in vitro)
cal Research Institute of Montreal, Montre-
tive Drug Screening Program.
experiments.
al, Quebec, Canada; and the Swiss Federal
In complex neuropsychiatric conditions, in-
Drug-to-target engagement also was con-
fectious diseases and cancer, Dr. Roth points
firmed in animal models of human disease.
out that for the past 20 years drug design has
In a mouse model of attention deficit hy-
Part of the funding for the research comes
been selectively aimed at a single molecu-
peractivity disorder (ADHD), mice missing
from the National Institutes of Health grants
lar target, but because these are complex
a particular dopamine receptor engage
supporting drug discovery receptor phar-
diseases, the drugs are often ineffective and
in recurrent aberrant behaviors similar to
macology.
Institute of Technology in Lausanne, Swit-
zerland.
decemBER 2012
19
News Welcome to the Area
Physicians
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Emergency Medicine
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Raliegh
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Cary
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Anesthesiology
Chapel Hill
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Carrboro
Family Medicine
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Family Medicine; Internal Medicine
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