A Cure for the Common Cold?
Abstract & Commentary
Synopsis: Studies of tremacamra, which competes with the cellular receptor for the virus, used prophylactically in humans with experimental rhinovirus infections showed efficacy in diminishing the incidence and severity of the common cold. While promising, the clinical usefulness of this strategy requires further study.
Source: Turner RB, et al. JAMA 1999;281:1797-1804.
In randomized, double-blind, placebo-controlled trials conducted in humans, experimental rhinovirus type 39 inoculation was tested with preinoculation or postinoculation administration of tremacamra or placebo. Tremcacamra was associated with decreased incidence of clinical colds (44% ± 11% vs 67% ± 9%), improved total symptom scores (9.6 ± 2.9 vs 17.6 ± 2.7), and decreased nasal mucus weight (14.5 ± 9.4 vs 32.9 ± 8.8 g) (P < 0.001 for all comparisons). Tremacamra was not associated with any adverse effects or evidence of absorption through the nasal mucosa and did not interfere with development of neutralizing antibody to rhinovirus.
Comment by Hal B. Jenson, MD, FAAP
We continue to search for the cure for the most common human infection, the common cold. Strategies that have been attempted include antivirals, which show some promise when used prophylactically but not once symptoms develop, and symptomatic treatments such as antihistamines, decongestants, and anti-inflammatory agents, all of which have limited efficacy and on only some but not all of the typical cold symptoms.
Of the 101 types of rhinoviruses, which account for 70% of upper respiratory tract infections, 90 types use intercellular adhesion molecule 1 (ICAM-1) as the cellular receptor for cell entry. This is the basis for this particular strategy to attempt to prevent or treat rhinovirus infections by intranasal administration of the soluble extracellular portion of the ICAM-1 molecule to compete with virion binding.
This study included both preinoculation and postinoculation administration, but both were actually prophylactic since clinical symptoms had not yet appeared. Thus, this strategy is not curative, but rather preventive. Tremacamra has been studied with one rhinovirus type 39, which appears to be particularly susceptible to the effects of tremacamra. The effects on the other rhinoviruses remain to be proved. Soluble tremacamra is cleared rapidly from the nasal mucosa. In these studies, two formulations were used—one solution and the other a mannitol-based powder with carboxymethylcellulose to retard clearance of the drug from the nasal cavity. Unfortunately, the carboxymethylcellulose was associated with nasal irritation. It is enticing that a strategy such as this actually shows efficacy, but we remain a long way from being able to use this clinically. (Dr. Jenson is Chief, Pediatric Infectious Diseases, University of Texas Health Science Center, San Antonio, TX.)
Tremacamra, a soluble adhesion intercellular molecule:
a. has been shown to be effective in infections caused by a majority of the 101 rhinoviruses that produce upper respiratory disease in humans.
b. appears to be systemically absorbed through the cells of the respiratory epithelium.
c. appears to act prophylactically against cold symptoms when administered either experimentally pre- or postinoculation of RSV type 39.
d. appears to interfere with the immune response to RSV infection.