TNF and CHF
By Sean Henahan, Access Excellence
Orlando, FL (11/12/97)- While deaths associated with high blood
pressure and atherosclerosis have been declining for decades, death from
heart failure has continued to increase. The discovery of the role of tumor
necrosis factor (TNF) in heart failure could represent an important new
treatment approach, according to a study presented at the American Heart
Association's annual meeting.
 Heart
failure occurs when the heart muscle is damaged from high blood pressure,
a heart attack or a defect such as a defective heart valve. The failing
heart keeps working, but is inefficient, resulting in fluid retention and
shortness of breath. The condition often progresses and becomes irreversible.
Moreover, numerous new drug treatments have failed to improve the outlook
for these patients.
Researchers presented data from a study of 18 patients with heart failure.
All of the patients had highlevels of TNF, a cytokine with powerful
inflammatory properties known to affect heart muscle. When TNF was inhibited
with an innovative recombinant protein, the patients' signs and symptoms
of cardiac failure improved. The patients typically were able to walk farther,
felt better, and showed improvement in heart function after the treatment.
Twelve patients received a single intravenous dose of TNF receptor,
while six were given placebo. On the first day of the study, individuals
receiving TNF receptor had an 85 percent drop in the amount of biologically
active TNF. The decreased level lasted in some patients for up to two weeks.
The single infusion was well tolerated and suppressed circulating levels
of biologically active TNF for at least two weeks in some individuals.
"This is not a cure by any means, but this study begins to address a
novel mechanism for why the disease progresses that has not been in previous
studies and we may have identified a novel target in heart failure," says
Douglas Mann, M.D., professor of medicine at Baylor College of Medicine.
The new treatment utilizes a recombinant TNF receptor which inactivates
the biological activity of TNF. The investigational protein binds
to TNF and prevents it from interacting with cell surface TNF receptors
which are on the cells in the heart and circulatory system. Patients
with heart failure have eight times as much TNF n their circulation as
do normal healthy individuals. Moreover, individuals with advanced heart
failure express the gene and make the protein, TNF, whereas the normal
heart doesn't express the gene and thus does not make this protein.
The researchers hope to conduct a larger trial with the TNF receptor
next year. TNF receptor is also undergoing clinical testing in other conditions
such as advanced rheumatoid arthritis and HIV.
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