The University of Nebraska Medical Center has begun a six-month research
project to test thalidomide as a possible treatment for people with Alzheimers
disease. In the 1960s, the drug was known for causing severe birth defects.
It was recently approved by the U.S. Food and Drug Administration as a
treatment for a skin condition associated with leprosy.
This will be the first collaborative study for Alzheimers disease patients
involving basic and clinical researchers associated with the UNMC Center
for Neurovirology and Neurodegenerative Disorders. The purpose of the center
is to combine clinical and basic research efforts in diseases of the brain
— such as AIDS and Alzheimer’s disease — that can lead to dementia.
Co-principal investigators of the study are William Burke, M.D., professor
of psychiatry and director of the division of geriatric psychiatry, and
Howard Gendelman, M.D., director of the UNMC Center for Neurovirology and
Neurodegenerative Disorders and professor of pathology/microbiology. Dr.
Burke also is co-director, chief of clinical affairs and director of Alzheimers
disease research for the center.
Thalidomide is a natural for this study, Dr. Burke said. It is a
potent modifier of the immune system. It turns off the cells in the brain
that produce harmful chemicals that can destroy nerve cells.
Ten patients will be enrolled in the six-month study to test the efficacy,
tolerability and safety of thalidomide. Patients will be randomly assigned
to receive either a placebo or 100 or 200 mg. of thalidomide. Participants
will be evaluated at an initial meeting, then again at six weeks, and three-
and six-month follow-up visits. The study is sponsored by Celgene, the
company that manufactures thalidomide.
Inflammation appears to be a common pathway to brain degeneration in
Alzheimers disease and AIDS-related dementia. More than 17 epidemiological
studies have shown that patients who take anti-inflammatory drugs may be
at lower risk for Alzheimers.
While its not clear which anti-inflammatory agents appear to reduce
risk, it appears the agents may have a role in disease modification and
prevention, Dr. Burke said. This study will help us determine if thalidomide
effects inflammation and degeneration of nerves in the brain associated
with Alzheimers disease.
These patients will have significant memory problems and will have
begun to experience difficulty in functioning independently, Dr. Burke
said. We want to be able to measure an improvement in the patients functional
activity and non-cognitive behaviors over a six-month time period.
One of the most interesting aspects of this study is the use of proton
magnetic resonance spectrometry (MRS) to test the effectiveness of thalidomide
in a non-invasive way.
The novel use of MRS is most exciting, Dr. Burke said. James McConnell,
M.D., associate professor, radiology, will conduct the MRS procedures.
MRS measurement techniques, which were developed earlier for an AIDS
study, will be adapted to the Alzheimers study and may change treatment
protocols. In the AIDS study, MRS examined the pattern and extent of cerebral
injury in HIV infection by monitoring metabolic response to therapies.
MRS gives biochemical information about the brain that conventional
methods of analysis cannot provide, and its clinical application has substantially
extended the diagnostic capability of neuroimaging, Dr. McConnell said.
In the next 20 years, billions of dollars may be spent on brain imaging
for dementia in the United States, Dr. McConnell said. The added use
of MRS may show us if newer treatments are working. Thats what this research
is all about improved treatment of patients with dementing diseases.
Ten participants are needed for the UNMC study. A small stipend is available.
Basic requirements for the study include early to middle stages of Alzheimers
disease, exhibiting mild to moderate impairment, which include problems
with daily activities such as driving, shopping, keeping a checkbook and
orientation to their surroundings. For more information, call (402) 559-5056.
UNMC is the only public academic health science center in the state.
Through its commitment to research, education and patient care, UNMC has
established itself as one of the country’s leading centers for cancer research
and treatment and solid organ transplantation. More than $34 million
in research grants and contracts are awarded to UNMC scientists annually.
In addition, UNMC’s educational programs are responsible for training more
health professionals practicing in Nebraska than any other institution.