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Publication Date: February 2009
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Chad Madill, Pharm.D. Candidate

Huntington's disease (HD) is a genetically pro-
grammed disease in which neuronal degeneration
occurs in certain areas of the brain. The degenera-
tion of neurons leads to uncoordinated, jerky move-
ments of the body called chorea, loss of intellectual
faculties, and uncharacteristic changes in mood and
behavior. These complications eventually lead to a
deteriorated quality of life and reduced life expec-
tancy. HD was first documented in 1872 by the
American physician George Huntington. The disease
affects about 1 per 10,000 people of European ances-
try with a slightly lower incidence rate in people of
Chinese, Japanese, or African descent. Individuals
with the adult-onset form of HD usually live 15 to 20
years after signs and symptoms appear. The adult-
onset form of HD develops anywhere between 30-50
years of age. Early-onset (juvenile) HD tends to be
more severe and individuals usually only live 10 to
15 years after signs and symptoms first present. Ju-
venile HD usually develops before the age of 20 and
accounts for 7-16% of all HD cases.1 This article will
review the signs and symptoms, genetics, mecha-
nism, and diagnosis of the disease to help provide an
insight on how specific drugs work. The main focus
will be on currently approved and investigational
treatment options for the management of HD.

HD can present through a variety of signs and
symptoms. In adult-onset HD, initial symptoms in-
clude chorea, unsteady gait, slurred speech, lack of
coordination, sleep disturbances, and chewing and
swallowing difficulty leading to weight loss and mal-
nutrition. Very slow movements and stiffness can
sometimes occur as the disease progresses. Many
people with the juvenile akinetic rigid variant of HD
(Westphal variant of HD) suffer from seizures (30-
50%), bradykinesia, and Parkinson-like symptoms.2
Cognitive deficits, including loss of executive func-
tion and memory, are seen frequently with disease
progression. Psychiatric symptoms such as aggres-
sion, anxiety, depression, egocentrism, and compul-
siveness are frequent in HD patients. Worsening of
addictions to alcohol and gambling, and hypersexual-
ity have all been reported.3

The Huntingtin gene (HTT) is located on the
short arm of chromosome 4 and it contains a se-
quence of trinucleotide repeats, CAG (cytosine, ade-
nine, guanine), on its 5' end. Repeats of CAG are
often called polyglutamine or polyQ since the amino
acid glutamine is derived from this trinucleotide se-
quence. The average human typically has 26 or less


11 ^ ^ ^ -^ ^ ^ ^ r fi

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i ^ ^ ^ ^^ ^ ^ ^ ^ ^^ ^ ^ ^ ^^ ^ ^ ^i^^ ^ ^ ^ j


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repeats of CAG within the HTT gene. In people with
HD, the CAG segment is repeated 36 to more than
120 times. Production of mutant Huntingtin gene
(mHTT) results in neuronal decay in certain areas of
the brain. A segment count of 27-35 repeats is clas-
sified as "intermediate" with the patient not likely to
be symptomatic but can still pass on the autosomal
dominant gene to successive generations. A segment
count of 36-39 repeats is classified as "reduced pene-
trance" in which a much later onset and slower pro-
gression of symptoms occurs compared with typical
HD. Many of these patients may die of other causes
before any HD symptoms are manifested. Repeats of
>39 glutamines is considered to be "full penetrance"
and a patient will be affected by HD. The length of
repeats correlates inversely with the age of onset and
the rate of progression of symptoms.4
Each offspring of an affected individual has a
50% chance of inheriting the mutant allele because
HD is inherited autosomal dominantly. All
"intermediate" and "reduced penetrance" carriers
have a chance of passing down fully penetrant HD.
Maternally inherited alleles are generally of the same
repeat length but paternally inherited alleles are gen-
erally of larger repeat length. In 1-3% of affected
individuals, no family history can be found, suggest-
ing a de novo mutation as the culprit for this rare
The function of Huntingtin (HTT) is unclear in
humans but in mice models it plays a vital role in
upregulating the expression of Brain Derived Neuro-
trophic Factor (BDNF) by acting as a transcription
factor. BDNF is a protein which protects neurons
and regulates neurogenesis; however, production of
BDNF is suppressed in mHTT models, leading to
progressive atrophy of certain areas of the brain. The
area of the brain with the most spiny neuronal loss is
the striatum, with the frontal and temporal cortices
affected to a lesser degree.5

In diagnosing HD, psychological and physical
examinations are used to determine symptoms ini-
tially. CT or MRI scans are used to determine
changes in brain structure if HD is suspected and a
definite diagnosis can be given with a blood test from
the suspected individual testing for the amount of
CAG repeats on each of the HTT alleles. If the re-
sults are unclear, the parents of the suspected individ-

ual can have blood tests done to help confirm the di-

Alleviating symptoms is the primary goal of
treatment and the focus of current treatment options
for this disease. The drugs used to treat movement
disorders of HD will be discussed first, followed by
the treatment of psychiatric and behavioral symp-
toms. Numerous investigational agents being re-
searched as possible breakthrough treatment options
for HD will be discussed later.
Tetrabenazine (Xenazine) is currently the only
FDA approved drug for the treatment of chorea in
HD and it is the first drug of any kind approved for
treatment of any symptoms associated with HD in
the US. In HD patients, there is an excessive amount
of dopamine located in nerve synapses within the
brain causing over excitation and allowing chorea
symptoms to be unmasked over time. Tetrabenazine
(TBZ) acts by decreasing the amount of dopamine at
these synapses, thus minimizing symptoms of cho-
rea. It selectively binds to the presynaptic vesicular
monoamine transporters (VMAT2) blocking reup-
take of dopamine, norepinephrine, and serotonin
from the cytosol into presynaptic vesicles. This proc-
ess secondarily decreases monoamine and serotonin
levels by increasing degradation of these molecules.
The process of VMAT binding and monoamine de-
pletion by TBZ is reversible, lasts hours, and is not
modified by chronic treatment. TBZ also antago-
nizes postsynaptic dopamine receptors. In a double-
blind, placebo-controlled study of 84 patients with
HD, TBZ was found to significantly reduce chorea
and provide a significant benefit on ratings of clini-
cal global improvement.6 In an evidence-based re-
view, Bonelli and Wenning reported that TBZ ap-
peared effective in reducing chorea in 7 out of 8
small level-II double-blind studies. In this review,
randomized controlled trials represent level-I studies
if the following are present: a minimum of 2 weeks
treatment period on active drug, a minimum of 10
HD patients on active drug completing the study, and
a full paper citation. If a randomized controlled trial
did not meet these criteria then it was classified as a
level-II study along with non-randomized or obser-
vational controlled trials. Level-III was assigned to
uncontrolled case series, i.e. retrospective reports and
open label trials.7 Frank et al. evaluated chorea
symptoms in 30 patients after abrupt TBZ with-

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drawal demonstrating an increase of chorea scores of
2.3 units from days 1 to 3 after withdrawal compared
to placebo. This study also demonstrated that sudden
withdrawal of TBZ up to 150mg appears safe.8 In-
somnia, depression, drowsiness, restlessness, dys-
phagia, and nausea have all been reported as possible
side effects of TBZ. In a single-blind, cross-over,
level-II study by Giminez-Roldan and Mateo, severe
depression occurred in 3 of 11 HD patients on TBZ
and 1 led to a suicide attempt.9 Decreasing the
amount of dopamine at different neuronal synapses
can cause depression and suicidal ideation in some
individuals; therefore, the FDA required a Risk
Evaluation and Mitigation Strategy (REMS) to help
ensure that the benefits outweigh the risks. A medi-
cation guide is required to be given to patients upon
dispensing as a result of this REMS. TBZ was
granted orphan drug designation by the FDA since
HD affects less than 200,000 individuals in the US.10
Haloperidol (Haldol), a widely established an-
tipsychotic drug, can be effective in ameliorating HD
-related chorea as demonstrated in 3 level II and 3
level III studies.7 Barr, et al. found low-dose halop-
eridol (< 10 mg/day) effective in reducing chorea in
an open pilot study with little added clinical benefit
at doses > 10 mg/day.11 Fluphenazine (Prolixin),
another typical antipsychotic, has shown effective-
ness in reducing chorea in a small level II trial, con-
firmed by level-III data and a case report.7 Haloperi-
dol and fluphenazine work by blocking postsynaptic
D2 receptors in the mesolimbic system and increase
dopamine turnover by blocking the D2 somatoden-
dritic autoreceptor. After about 12 weeks, depolari-
zation of the dopamine tract occurs and there is a sig-
nificant decrease in dopamine neurotransmission.12
Both of these typical antipsychotic are known to
cause extrapyramidal symptoms (EPS) so close
monitoring is necessary.
Atypical antipsychotics have also been evaluated
for treating movement disorders associated with HD.
Olanzapine (Zyprexa) improved behavioral sub-
scores with low doses (5mg/day) in 2 level III stud-
ies, but higher doses (up to 30mg/day) significantly
reduced not only chorea, but also orolingual dysfunc-
tion, finger dexterity, and gait in an additional level
III study. In a series of case reports, Risperidone
(Risperdal) appears to be useful for the treatment of
HD associated psychosis and chorea. Quetiapine
(Seroquel) and ziprasidone (Geodon) have both
been shown to increase motor function of the Unified

HD Rating Scale (UHDRS) in other case reports.
Clozapine (Clozaril) has been the best documented
drug but has shown the least efficacy and the most
severe SE's including leukopenia.7 The atypical an-
tipsychotics generally cause less EPS than the typical
antipsychotics due to less D2 receptor antagonism
and more 5-HT2 receptor blockade.12
In the last decade, glutamate has been postulated
to play an important role in HD, in part because in-
trastriatal injections of glutamate agonists (especially
NMDA receptor agonists) produce the symptoms of
HD.13 In transgenic HD models, glial glutamate re-
uptake transporters are decreased which ultimately
results in increased synaptic glutamate.14 Some evi-
dence suggests NMDA receptors are more sensitive
to intracellular Ca2+ influx and excitotoxicity when
mHTT protein interacts with them.15 Amantadine
(Symmetrel) and memantine (Namenda) both have
inconclusive evidence regarding their usefulness in
HD. Amantadine has not established a clear mecha-
nism of action but some suggest it is similar to me-
mantine which acts as a low to moderate noncom-
petitive antagonist of NMDA receptors. Blockade of
these receptors leads to a decreased excitatory state,
in turn, decreasing Ca2+ influx and preventing further
nerve damage to the brain.12 Vernagen-Metman, et
al. published a high-quality level-I study demonstrat-
ing amantadine (400 mg/day) lowered chorea scores,
with a median reduction in extremity chorea at rest
of 36% for all 22 valuable patients.16 In contrast, a
high-quality, level-I randomized, placebo-controlled,
cross-over trial conducted by O'Suilleabhain and
Dewey demonstrated that 2 weeks of treatment with
amantadine (300 mg/day) did not have any effect on
chorea in HD patients.17 Multiple lower level studies
and case reports confirmed this. Amantadine may
increase irritability and aggressiveness in HD pa-
tients, thus it is unclear what role this drug may play
in the treatment of HD. 7Memantine, which is used
frequently to diminish dementia symptoms in Alz-
heimer's patients, might play a role in HD. Meman-
tine can retard HD progression by decreasing motor
function decline. Beister, et al. conducted a two-year
study with memantine (up to 30 mg/day) in 27 HD
patients recruited from two different clinics. The
results suggested that the placebo group had a 21.2%
decrease in motor function over 2 years compared to
4.3% in the memantine group, however further re-
search is needed.18
Myoclonus is a rare feature of HD and antidopa-

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Table 1. Summary of Clinical Trials for the Management of Neurodegenerative Symptoms in Huntington's Disease


Study Group

Frank, et al.

Gimenez, et al.

Barr, et al.

Metman, et al.

et al.

Beister, et al.

Saft, et al.

Puri, et al.

TBZ, n=54
Placebo, n=30

Withdrawal (W) of TBZ, n=12
Partial Withdrawal (PW), n=12
No Withdrawal (NW), n=6

TBZ Haloperidol, n=11

Haloperidol, n=10
Placebo, n=10

Placebo -> Amantadine, n=12
Amantadine -> Placebo, n=12

Placebo -> Amantadine, n=14
Amantadine -> Placebo, n=11

Memantine, n=24
Placebo, number not reported

Valproic acid, n=8

Ethyl-EPA, n=67
Placebo, n=68

Tetrabenazine: up to 100 mg/day
for 12 weeks

Tetrabenazine: withdrawal of TBZ
from patients on stable
therapy for at least 2 months

Tetrabenazine: varied dose

Haloperidol: 1 to 40 mg/day





Amantadine: 400 mg/day for 2 weeks Antichorea

Amantadine: 300 mg/day for 2 weeks Antichorea

Memantine: up to 30 mg/day for 2

Valproic acid: 300 to 2700 mg/day

Improved Motor

Improved Myoclonic

Ethyl-EPA (purity > 95%): 2 gm/day for Improved Motor
12 months Function

5.0 unit decrease in chorea severity with active group compared
to 1.5 unit decrease with placebo (p<0.0001)

Adjusted mean chorea scores for W group increased by 5.3 units
from day 1 to 3, vs. those in the combined PW and NW groups
increased by 3.0 units (p=0.0773).

Though improvement in chorea scores over baseline was greater
with TBZ, 46.3 (23.4), vs. haloperidol, 28.6 (47.7), the difference
did not reach statistical significance.

Significant improvement of abnormal movements, >30% from
baseline, occurred at concentrations of 2-5ng/ml, corresponded to
doses of 1.5 to 10mg/day. Further improvement at serum concen-
trations above this range was minimal.

Chorea scores lower with amantadine (usually 400 mg/d) vs. pla-
cebo, median reduction in extremity chorea at rest = 36% (p=0.04)
for all 22 valuable patients and = 56% in 10 individuals with high-
est plasma drug levels. Improvement correlated with plasma
amantadine concentrations (p=0.01) but not CAG repeat length.

Chorea was not significantly affected by amantadine therapy. The
chorea score was 9.6 (3.1) at baseline and 9.7 (3.7) on aman-
tadine. 95% confidence interval was -1.43 to 1.0. Despite this, 19
subjects felt improved during the amantadine phase vs. 6 subjects
in the placebo phase (p=.006) and the quality of life was better

Memantine treatment of HD may be useful to retard progression
of the disorder

In 7 patients myoclonus and UHDRS motor score improved in a
dose dependent manner. Initial mean UHDRS motor score = 73.1
( 11.9), after treatment mean UHDRS motor score = 60.2 ( 12.8)
(p=0.042). 3 patients had antidopaminergic medication reduced.

Ethyl-EPA had no benefit in the intent-to-treat cohort of patients
with HD (p<0.05); exploratory analysis: significantly higher number
of patients in per protocol cohort showed stable or improved mo-
tor function (p=0.06).

minergic medications are not typically effective for
this problem. Myoclonus is normally associated
with juvenile onset HD but this is not always the
case. Numerous studies have shown the beneficial
effect of valproic acid (Depakote) on reducing myo-
clonus but not in reducing involuntary movements in
choreatic hyperkinesias. Saft, et al. conducted a case
-series that investigated over 600 people with HD.
Eight of these patients had myoclonus as the main
clinical symptom. Patients were scored by Unified
Huntington's Disease Rating Scale (UHDRS) motor
scores before and after treatment with valproic acid.
Seven of the 8 patients had remarkable improve-
ments in their motor function scores. An additional
mood-stabilizing effect was observed in 5 cases and
the 1 patient who did not show improvement was
taking a daily dose of only 300 mg of valproate. All
other patients were taking valproic acid 900-
2700mg/day. Furthermore, mobility and manual
dexterity were remarkably improved in these pa-
tients. Valproic acid's ability to increase GABA lev-
els in the brain may explain its effectiveness in treat-
ing myoclonus which has been speculated to be
caused by GABA deficiency.19 Valproic acid may
be a plausible option for use in myoclonic hyperkine-
sia-dominant HD with the validation of future stud-
Approximately 80% of patients with HD suffer
from some level of dystonia. Less commonly, pa-
tients suffer from severe functional impairment in
which therapeutic intervention is required. In some
individuals, chorea symptoms begin to lessen as the
disease progresses and more functional capacity is
lost. Sustained, involuntary torsion, called dystonia,
begins to dominate as the primary motor dysfunction
in these people.20 Typical pharmacological treatment
options for dystonia include anticholinergics, benzo-
diazepines, baclofen, dopaminergic agents, dopamine
-depleting agents (rarely used), and botulism toxin
Depression is the most frequent psychiatric
symptom associated with HD and it normally starts
as an isolated symptom. Beneficial results from case
reports in HD patients have been reported for
amitriptyline (Elavil), imipramine (Tofranil),
fluoxetine (Prozac), phenelzine (Nardil), isocar-
boxazid (Marplan), amoxapine, and mirtazapine
(Remeron). Psychosis is another symptom seen in
approximately 3 to 12% of HD patients. This symp-
tom ranges from nonspecific paranoia to presenta-

tions similar to schizophrenia.7 A case study con-
ducted by Erdemoglu and Boratav demonstrated that
risperidone (Risperdal) offers clinical improvement
for patients affected by psychosis.21
Frontal lobe dysfunction can cause increased irri-
tability, lack of control, and aggression in some HD
patients. Haloperidol was useful in treating irritabil-
ity, depression, and aggressive outbursts in a double-
blind, crossover level-II study. Olanzapine also
showed a significant improvement in the UHDRS
psychiatric subscores of depression, obsessions, irri-
tability, and anxiety in 2 small level-III studies.
According to DSM-III-R criteria of sexual disor-
ders, 82% of HD patients experience one or more of
these problems. Some patients may exhibit hyper-
sexuality but sexual hypoactivity is more common.
Two case reports show that leuprolide (Eligard) and
medroxyprogesterone (Provera, Amen) have been
successful in the treatment of hypersexuality. 7 Both
of these agents act by decreasing the body's natural
release of GnRH from the pituitary resulting in re-
duced steroidogenesis.12
Dementia is one of the three cardinal clinical fea-
tures of HD and its prevalence depends on the clini-
cal stage of the disease. It often subtly affects those
who are asymptomatic gene-carriers of HD. Choline
esterase inhibitors have been mostly ineffective in
level-III trials and 1 case report, but galantamine
(Razadyne) has shown some promising results in
multiple studies.' Galantamine's ability to modulate
the nicotinic acetycholine receptors (nAChRs) via
allosteric potentiation possibly contributes to its neu-
roprotective properties. Park, et al. conducted a
study showing reduced neurological deficits and de-
creased mean striatal lesion volume in the galan-
tamine treatment group compared to placebo.22 A
possible reason for this might be from the allosteric
potentiation of nAChRs leading to an up-regulation
of bcl-2, an anti-apoptotic protein, causing suppres-
sion of apoptosis.23 Galantamine exerts anti-
oxidative effects by reducing oxidative damage, and
restoring mitochondria membrane potential.24 It is
also a reversible inhibitor of acetylcholinesterase
(AChE) thus decreasing the breakdown of acetylcho-
line.12 Galantamine seems to offer hope for HD pa-
tients although evidence is limited.
Unsaturated fatty acids and minocycline
(Minocin, Solodyn) have provided mild cognitive
improvement in a few open label trials.7 Mino-
cycline has been studied numerous times as a possi-
ble neuroprotective agent for use in HD and other

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Table 2. Summary of Animal Studies for the Management of Neurodegenerative Symptoms in Huntington's Disease

Thomas, et al. HDACi 4b: 150 mg/kg/d for 67 days Improved Motor Brain weight significantly greater compared to placebo-
(2008)32 Function treated mice (407.3 mg vs. 345.4 mg; p=0.045). Signifi-
cant differences in motor performance

Park, et al. Galantamine: 1 mg/kg/d or 10 mg/kg/d Neuroprotection Two doses of galantamine (1 mg/kg/day and 10 mg/kg/
(2008)22 twice daily for 5 days day) delayed the onset of neurologic impairments and
decreased the mean neurological impairment scores
(p<0.05). The dose-dependent benefit of galantamine
was not significant.

Choi, et al. Minocycline: 45 mg/kg/d for 3 weeks Neuroprotection Minocycline reduced neuronal death and attenuated
(2007)25 learning and memory impairment. % of eosinophilic
cells vs. total cells in dentate gyrus was 52.38% (placebo
-treated) vs. 12.70% (minocycline) (p<0.05).

Mievis, et al. Minocycline: 10 mg/kg/d for 14 days Neuroprotection No improvement in survival, weight loss, or motor func-
(2007)27 tion in treated mice. Minocycline failed to mitigate the
ventricle enlargement and the striatal and cortical atro-

various cognitive deficit diseases. A study by Choi,
et al. concluded that minocycline administration at-
tenuated deficits in learning and memory in amyloid
beta peptide(1-42)-infused rats.25 Minocycline's
neuroprotective proposed mechanism of action is
related to its inhibitory activity on inflammation and/
or apoptosis, both phenomena being closely associ-
ated with neurodegeneration.26 A contradicting
study by Mievis, et al. showed no benefit with mino-
cycline in survival, weight loss, motor function, or
mitigation of the ventricle enlargement, as well as
the striatal and cortical atrophies induced by the
transgene.27 Omega-3 fatty acid EPA shows promis-
ing evidence of decreasing symptoms and motor dys-
function in 1 case report and 1 clinical trial.28 Con-
versely, other trial data has found no significant dif-
ference in symptoms from the group of HD patients
receiving 2g/day of ethyl EPA versus placebo.29 Ex-
ploratory analysis revealed that a significantly higher
number of patients in the per protocol cohort, treated
with ethyl-EPA, showed stable or improved motor
function though. Unsaturated fatty acids and mino-
cycline are still being investigated for a possible role
in future HD treatment strategies.
It has been proposed that CNS trauma during
acute and chronic neurodegeneration can cause cyto-
chrome c release from mitochondria into the cyto-
plasm of cells, activating an enzyme pathway ulti-
mately leading to cell death. Multiple drugs have

been investigated which inhibit the release of cyto-
chrome c from mitochondria, inhibit caspase activa-
tion, and block cell death. Wang and colleagues ex-
amined over 1040 compounds in an attempt to find
drugs that inhibited cytochrome c release and lacked
major side effects or penetration into the CNS.30 The
study identified 21 compounds, 16 of which were
protective in a cellular model of cell death. A few of
the more common drugs which showed inhibition of
cytochrome c release and have some promise for the
future were minocycline, doxycycline (Doryx),
methazolamide (Neptazane), and melatonin. Ulti-
mately, if cytochrome c release proves significant in
HD, these pharmacological agents could emerge as
alternative treatment options.
Another investigational medication in HD is tre-
halose, a supplement that inhibits cytokine release by
working early in the inflammatory process and thus
decreasing the limiting effects of HD on neurons.
Trehalose is a disaccharide sugar found in nature that
protects cells from a wide range of environmental
stressors. It is postulated that trehalose increases the
destruction of mHTT.31
Another experimental compound showing prom-
ise is a drug that inhibits HDAC 4 and thus is cur-
rently called HDACi 4b. HDAC 4 may be an impor-
tant enzyme in promoting HD activity and HDACi
4b selectively binds HDAC 4 but does not inhibit the
body's other important HDAC enzymes. Thomas, et

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Volume 24, Issue 5 February 2009

al. studied Huntington mice presenting with signs of
motor dysfunction in which this compound was
given to half of the mice while the other half were
given placebo. A significant improvement in motor
function scores was seen in the treated HD mice
compared to placebo (288 vs. 250, respectively,
P=0.02). All mice were trained on an AccuRotor
rotarod at 3 months of age to establish baseline mo-
tor scores for each subject. These results were com-
pared to the scores of the treatment and placebo
groups once HDACi 4b was initiated. Hindlimb
clasping, reduced global activity in a freely moving
environment, hindlimb dystonia, and truncal dystonia
(kyphosis) were all used as markers to establish mo-
tor scores. HDACi 4b caused a decrease in the ex-
pression of genes associated with cell death, cell cy-
cle, and the immune response which could ultimately
provide neuroprotection. HDACi 4b prevented
dystonic posture and dramatically improved the
physical appearance of the treatment group. Brain
weight was significantly higher in the treatment
group compared to placebo (407.3mg vs. 356.4mg,
respectively, P=0.045). HDACi 4b has shown less
toxicity and greater benefits in mice than other previ-
ous HDAC inhibitors.32

There is still much to be learned about HD and
its treatment. Successful treatment for this disease is
crucial since adult-onset HD usually runs its full ter-
minal course in 10 to 30 years after signs and symp-
toms appear and in only 10 years with juvenile HD.
Most patients become bedridden by the final stages
of HD and normally die from complications such as
pneumonia, heart failure, and injuries related to falls.
HD is a serious disease that can present with symp-
toms of chorea, aggression, depression, cognitive
deficits, along with many other physical and mental
detriments. Tetrabenazine, typical and atypical an-
tipsychotics, valproic acid, galantamine, memantine,
amantadine, minocycline, doxycycline, HDACi 4b,
and other drugs have shown promise in HD. The
hope of investigational and future treatment options
keeps the future bright for such a dark disease.

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13. Beal MF, Ferrante RJ, Swartz KJ, et al. Chronic qui-
nolinic acid lesions in rats closely resemble Hunting-
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17. O'Suilleabhain P, Dewey RB, Jr. A randomized trial
of amantadine in Huntington disease. Arch Neurol
2003; 60(7):996-8.

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18. Beister A, Kraus P, Kuhn W, et al. The N-methyl-D-
aspartate antagonist memantine retards progression of
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Supplement 2004; 68:117-22.
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20. Louis ED, Lee P, Quinn L, et al. Dystonia in Hunting-
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striatal degeneration in 3-nitropropionic acid model of
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23. Ezoulin MJ, Ombetta JE, Dutertre-Catella H, et al.
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24. Geerts, H. Indicators of neuroprotection with galan-
tamine, Brain Res. Bull 2005; 64:519-24.
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26. Blum D, Chtarto A, Tenenbaum L, et al. Clinical po-
tential of minocycline for neurodegenerative disor-
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ease transgenic mice. PNAS 2008; 105(40): 15564-9.


Levetiracetam Going Generic

In January 2009, the FDA granted letters of ap-
proval for the production of generic levetiracetam
subsequent to the patent expiration of Keppra
(UCB Pharma, Inc.; Brussels, Belgium). Generic
levetiracetam is available as 250 mg, 500 mg, 750
Smg, and 1,000 mg tablets as well as an oral solution
of 100 mg/mL. The extended-release, oral formu-
lation of levetiracetam, recently approved for ad-
ljunctive therapy in partial seizures among those
aged > 16 years is not generically available at pre-
sent and is marketed under the trade-name Keppra-

Febuxostat (Uloric) Takeda Pharmaceuticals,

This month the FDA approved febuxostat for
the chronic management of hyperuricemia in per-
sons with gout. Febuxostat is an oral, selective
xanthine oxidase inhibitor and differs from al-
lopurinol in that it does not structurally resemble
purines or pyrimidines. Look for more information
on febuxostat and other emergent therapies for the
Management of hyperuricemia and gout in an up-
coming edition of PharmaNote.

The PharmaNote is Published by:
The Department of Pharmacy
Services, UF Family Practice Medical
Group, Departments of Community
Health and Family Medicine and
Pharmacy Practice

John G. Gums Editor
PharmD, FCCP

R. Whit Curry, MD Associate Editor

Steven M. Smith Assistant Editor

PharmaNote Volume 24, Issue 5 February 2009


Volume 24, Issue 5 February 2009

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