New Study Suggests Antiepileptic Drug Levetiracetam May Benefit Patients With Parkinson's Disease

SAN FRANCISCO, CA -- (MARKET WIRE) -- 04/29/2004 -- In patients with Parkinson's disease, the antiepileptic drug
levetiracetam (Keppra®) reduced the involuntary movements (dyskinesia) associated with levodopa, the medication most
commonly used to treat Parkinson's disease, according to a study presented today at the 56th annual meeting of the
American Academy of Neurology.(1) The independent study is one of the first to specifically evaluate an antiepileptic
drug for the treatment of levodopa-induced dyskinesia in Parkinson's patients.

"Levodopa-induced dyskinesia remains one of the biggest challenges in treating Parkinson's disease because it is a
common side effect and is difficult to manage," said lead investigator Theresa Zesiewicz, M.D., assistant director of
the Parkinson's Disease and Movement Disorders Center, and associate professor of neurology at the University of South
Florida. She explained that levodopa can effectively control Parkinson's disease symptoms -- stiffness, slow movement
and tremors -- but after five to eight years, it often causes the side effect of dyskinesia. "Our study showed
levetiracetam reduced dyskinesia and, importantly, did not interfere with the efficacy of levodopa in controlling
Parkinson's disease symptoms," she said. An anticonvulsant with a novel mechanism of action, levetiracetam is currently
approved by the U.S. Food and Drug Administration for the adjunctive treatment of partial-onset seizures in adults.

Study and Findings

The prospective, open-label pilot study included nine Parkinson's disease patients (three women and six men, average
age 65 years) being treated with levodopa and who were experiencing peak-dose dyskinesia for at least 25 percent of
their waking hours. Two patients dropped out before completing their diaries, leaving seven patients for the efficacy
analysis. Ten days of treatment with levetiracetam resulted in changes suggesting improvement in levodopa-induced
dyskinesia. Further analysis after 60 days of treatment with levetiracetam yielded the following results:

--  A significant increase in "ON" time without dyskinesia or with non-
    troublesome dyskinesia by 42 percent, from 43 percent at baseline to 61
    percent at 60 days (p = 0.02).  ON time refers to the time when levodopa or
    other medications effectively treat the symptoms of Parkinson's disease.

--  A trend for decreased ON time with troublesome dyskinesia by 52
    percent, from 23 percent at baseline to 11 percent at 60 days (p = 0.13)

--  No significant change in OFF time (31 percent at baseline vs. 27
    percent at 60 days).  OFF time occurs when Parkinson's disease medications
    no longer control the disease symptoms, resulting in slowness, stiffness
    and immobility.

--  Improved the clinical global impression (CGI) of dyskinesia in six
    patients (improvement was marked in one, moderate in two and minimal in
    three), and one reported no change or worsening in dyskinesia.

There were no significant changes in other standard measures, including the Abnormal Involuntary Movement Scale (AIMS)
and the Unified Parkinson's Disease Rating Scale (UPDRS).

In the study, levetiracetam was administered at a starting dose of 250 mg/day and escalated up to as much as 3000 mg
over a 60-day period. The investigators evaluated the patients at baseline and every 10 days thereafter, assessing the
amount of ON time with no dyskinesia, with non-troublesome dyskinesia, and with troublesome dyskinesia; OFF time; and
CGI, AIMS and UPDRS scores.

Of the nine patients who started the study, five withdrew due to side effects, the most frequent being increased
somnolence (sleepiness), which occurred in three patients. One patient withdrew because of obtundation (dulled or
reduced level of alertness or consciousness) and one due to dizziness and confusion.

"Many Parkinson's disease patients experience somnolence, either from the disease itself or from medications used to
treat it -- so they may be more susceptible to somnolence from levetiracetam than are patients with epilepsy," said Dr.
Zesiewicz. Because levetiracetam, nonetheless, appeared to be beneficial in reducing the dyskinesia, she recommended
that "future studies in Parkinson's disease patients start with a lower dose and titrate more slowly."

About Parkinson's Disease

Parkinson's disease (PD) is a chronic and severely debilitating neurodegenerative disorder that affects more than two
million people worldwide, and at least 750,000 people in the United States. PD is associated with bradykinesia (slowed
movements), tremor, rigidity and postural instability. While PD most commonly affects people beginning in their 60s, it
can occur as early as age 20, and as many as 10 percent of cases occur before age 40.(2)

PD is caused by degeneration of the substantia nigra (SN), a part of the brain involved in movement control. Cells in
the SN interact with other movement control centers by secreting a neurotransmitter (a substance that transmits signals
from nerve to nerve) known as dopamine. When these "dopaminergic" neurons in the SN die, the other centers become
unregulated, resulting in most of the movement-related symptoms of PD.2 Most PD medications either mimic the effect of
dopamine, increase dopamine levels or extend the action of dopamine in the brain. Levodopa, commonly known as L-dopa,
has been the traditional drug used for treatment, but it can cause side effects (e.g., spasmodic movements, called
dyskinesia) and tends to become less effective over time.(3) Various brain surgical procedures are also used in severe
cases of PD; research on other therapies, such as stem cell implantation, is underway.

About The University of South Florida College of Medicine

Responding to demand from Tampa's community leaders, the University of South Florida (USF) College of Medicine was
established by the Florida Legislature in 1965. Part of the USF Health Sciences Center, doctors and researchers were
awarded nearly $88 million in grants and contracts last year. Providing advanced medical care, USF Physicians Group at
the College of Medicine is the largest doctor group in West Central Florida offering expert medical care throughout
Tampa Bay's finest hospitals such as Tampa General Hospital, James A. Haley Veterans' Hospital, Moffitt Cancer Center
and All Children's Hospital. With a reputation for training high performing clinical physicians, the College is proud
that more than half of its physician-graduates remain in Florida to practice medicine.

References

(1) Zesiewicz TA, Sullivan KL, Maldonado JL, Tatum WO, Hauser RA. Levetiracetam (Keppra) in the treatment of levodopa-
induced dyskinesia in Parkinson’s disease. Poster 138 presented at: 56th annual meeting of the American Academy of
Neurology, April 24 - May 1, 2004, San Francisco, CA.

(2) We Move. Parkinson’s disease – frequently asked questions. http://www.wemove.org/par/par_faq.html. Accessed
February 27, 2004.

(3) MayoClinic.com. Parkinson’s Disease. http://www.mayoclinic.com/invoke.cfm?id=DS00295. Accessed February 27, 2004.

Contact:
Janene Ferrara
Chandler Chicco Agency
646-479-6677
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Anne DeLotto Baier
University of South Florida
813-974-3303 or 813-598-0643
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SOURCE: Market Wire (press release)
http://www.marketwire.com/mw/release_html_b1?release_id=66520

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