By Neil Osterweil

If standard therapies don’t give relief to patients with refractory cough associated with interstitial lung disease, maybe a little poison could do the trick.

Among 41 patients with idiopathic interstitial pneumonia with autoimmune features (IPAFs) who had intractable cough, treatment with the traditional Chinese medicine semen strychni was associated with a significant improvement in patient-reported outcomes, reported Mingwan Su, MD, from Guang’anmen Hospital and the China Academy of Chinese Medical Sciences in Beijing, China.

“Semen strychni is associated with reduction in cough and can be an effective drug therapy for refractory cough in association with IPAFs,” she said in an oral abstract session at the American College of Chest Physicians (CHEST) 2024 Annual Meeting.

Semen strychni is derived from the dried seeds of the plant Strychnos nux-vomica L. Its main toxic component is strychnine, the poison said to be favored by legendary mystery writer Agatha Christie.

Semen strychni is a central nervous system agonist that has reported efficacy in the treatment of musculoskeletal and autoimmune conditions, including rheumatoid arthritis, myasthenia gravis, and amyotrophic lateral sclerosis.

The medication also has immunomodulatory properties, Su said, and is thought to have beneficial effects against cough associated with IPAFs by reducing hypersensitivity.

Case-Control Study

To test this, Su and colleagues conducted a single-center retrospective study of the effects of semen strychni on 41 patients with IPAF-associated cough who were treated with low-dose oral semen strychni 300 mg/d for 2 weeks. These patients were paired with 41 control individuals matched for age, sex, and disease course. Control individuals received standard of care therapies.

The investigators found that for the primary endpoint of a change in the visual analog scale (VAS) at 2 weeks, there was a significantly greater reduction from baseline among patients treated with semen strychni compared with control individuals, with a baseline mean VAS score of 4.9 reduced to 2.1 at the end of treatment, vs 4.6 pre- to 3.3 post-treatment for control individuals. This difference translated to an odds ratio (OR) favoring semen strychni of 0.75 (P < .001).

In addition, the toxic compound was also associated with greater patient-reported improvement in the quality of life, as measured using the Leicester Cough Questionnaire, a 19-item scale that measures quality of life for people with chronic cough. Patients in the experimental arm had mean scores of 11.9 before treatment and 19 at the end of therapy compared with 12 and 15.1 points, respectively, among individuals in the control arm. This translated to an OR of 3.8 (P < .001) for patients on semen strychni.

The toxin appeared to be generally safe. There were no reported cases of pain, fainting, or bleeding in either study group, although there was one case of muscle twitching in the semen strychni group, Su reported.

There is evidence to suggest that semen strychni may have a calming effect on cough through action in the STAT3 pathway, considered to be a promising therapeutic target for musculoskeletal conditions, Su noted.

Not Ready for Prime Time

“My feeling is that these kinds of abstracts are welcome, but this is far from reality at this point,” commented Vijay Balasubramanian, MD, clinical professor of medicine and director of the Pulmonary Hypertension Program at the University of California San Francisco.

“We need some kind of a regulated way of understanding dose characteristics and pharmacokinetics, and so it should be followed by more systematic studies,” he said in an interview.

Both Balasubramanian and his co-moderator Andrew R. Berman, MD, director of the Division of Pulmonary and Critical Care Medicine and Allergy and Rheumatology at Rutgers Health New Jersey Medical School in Newark, New Jersey, said that they sympathize with clinicians and their patients who seek out unusual therapies such as semen strychni.

“It’s very frustrating to treat chronic cough, especially associated with fibrotic lung disease, and the extent to which researchers will go to find that one product that perhaps can make a difference is understandable,” said Berman.

Su did not report a study funding source. Su, Balasubramanian, and Berman reported no relevant financial relationships.