Chromosome Length May Indicate Development of Respiratory Infection

The rate of experimentally induced upper respiratory infection increased in healthy adults with shorter telomere length (a structure at the end of a chromosome) in specific leukocytes, according to research in JAMA. The results were identified in comparison to participants with longer telomeres.

Telomeres, DNA-protein complexes at the end regions of chromosomes, decrease in length with every cell division.

“Telomere shortening in leukocytes (white blood cells) has implications for immunocompetence and is associated with increased synthesis of proinflammatory cytokines and poorer antibody response to vaccines,” according to background information accompanying the article. “Shorter leukocyte telomere length also is associated with aging-related morbidity and mortality from conditions with immune system involvement, including infectious diseases, cancer, and cardiovascular disease.”

Investigators assessed telomere length in 152 healthy adults, then quarantined participants to administer nasal drops containing a common cold virus; participants were then monitored for 5 days for development of infection and clinical illness.

Among all patients, 69% developed respiratory infections and 22% developed a cold. An association was seen between those with shorter telomere lengths in all 4 cell types and increased odds of infection following exposure to the virus.

Those with the shortest CD8CD28 telomere length had a rate of infection of 77%, compared to 50% for those in the group with the longest telomeres. Among participants with the shortest telomeres, 26% became clinically ill. The rate for clinical illness was 13% for those in the group with the longest telomeres.

“In this study of healthy young and midlife adults, shorter CD8CD28 cell telomere length was associated with upper respiratory tract infection and clinical illness following experimental exposure to rhinovirus,” the authors concluded. “Because these data are preliminary, their clinical implications are unknown.”

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Antidepressant clomipramine can ease the symptoms of multiple sclerosis,

Antidepressant drug clomipramine may help combat the course of multiple sclerosis (MS), suggests a study. As yet, drugs for this type of MS have been virtually non-existent. In MS patients, leukocytes damage the layer surrounding nerve cells, the so-called myelin sheath. This results in neurological disturbances; in 85 percent of patients, the disease is characterised by clearly defined relapses and may cause e.g. visual impairment, paralysis or numbness. The majority of patients experience gradual deterioration after 15 to 20 years, which is referred to as progression. In ten percent of the patients, the disease is progressive from the outset, without any relapses along the way.

Researchers  screened 1,040 generic therapeutics and, based on pre-clinical studies, identified one that is suitable for the treatment of multiple sclerosis. Today, twelve drugs have been approved for the treatment of relapsing-remitting multiple sclerosis; for the progressive types, on the other hand, only a few therapy approaches exist. “The mechanisms causing damage in progressive MS are not always the same as in relapsing-remitting MS. This is why the latter requires different therapeutic approaches,” says a researcher. 

The team worked with approved drugs, the side effects of which have already been amply documented. From among those drugs, the researchers selected 249 well-tolerated therapeutics that enter the nervous system safely; this is where chronic inflammation occurs in progressive MS. Using cell cultures, they tested which of the 249 substances are capable of protecting nerve cells from the damaging influence of iron. In MS patients, iron is released due to cell damage, damaging nerve cells in turn.

Following those tests, 35 potential candidates were identified; the researchers subsequently analysed them with regard to additional properties: investigating, for example, if they can reduce damage to mitochondria – the powerhouses of the cells – or if they minimise the activity of leukocytes that attack the insulation of nerve cells in MS patients. In the process, the drug clomipramine proved promising.

In the next step, the researchers analysed the substance in mice suffering from a disease comparable with relapsing-remitting multiple sclerosis in humans. The therapy suppressed the neurological disturbances completely; as a result, damages to the nerve cells and inflammation were minimised. In a subsequent test, they treated mice with a disease that resembles progressive MS in humans. Here, too, the therapy proved effective, provided the researchers applied it immediately after the first clinical symptoms became apparent. Symptoms such as paralysis were thus reduced – unlike in control animals that were treated with placebo drugs. 

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