By Tyra Martinez
Telomeres are located at the ends of chromosomes and protect your genetic information from deteriorating or fusing with other chromosomes. If a cell has critical telomere shortening it can lead to degradation or apoptosis. Unrepaired telomere damage can also cause organ failure, bone marrow failure, liver cirrhosis, pulmonary failure and cancer. Research by Townsley et al. suggests danazol can promote telomere elongation in people with certain genetic predispositions. Despite the promising results shown by Townsley et al., danazol has complications.
Townsley et al. selected participants with telomere length below the first percentile, a genetic mutation in telomere repair gene, low blood counts, and history of pulmonary failure. Every participant meeting this criteria had their DNA sequenced to determine a genetic underpinning for telomere degradation. Once screened, all participants were administered 800 mg of danazol (400mg twice a day) for two years.
Favorable Results
The first part of the study sought to determine if danazol could prevent telomere reduction. During the initial stages of the experiment 11 of the first 12 participants showed remarkable increase in telomere elongation. The National Heart, Lung, and Blood Institute (NHLBI) deemed this preliminary phase of the study successful and granted permission to continue to subsequent stages (Figure 1).
The second part of the study evaluated danazol treatments on all eligible participants in relation to other complications attributed with telomere degradation, such as low blood counts, liver and pulmonary failure. The danazol treatments had a positive effect on the hematologic responses of the participants. Almost all the patients that were dependent on blood transfusions prior to the study were showing improvements in their hematologic responses. Townsley et al. noted 7 participants with pulmonary function results prior to the study didn’t show significant changes in their pulmonary issues with the treatments of danazol.
Unfavorable Results
Townsley et al. saw less favorable results regarding pulmonary issues. Throughout the study the pulmonary fibrosis levels remained stable although one participant died due to pulmonary failure via pneumonia. Ten patients withdrew from the study due to side effects – two from moderate adverse effects and three from higher grade adverse effects. The researchers stated there were common side effects: “The most common adverse events were elevations in liver-enzyme levels (in 41% of the patients), muscle cramps (in 33%), edema (in 26%), and lipid abnormalities (in 26%)” (Townsley et al., 2016). Of the other five participants that withdrew, one died as mentioned above and two sought alternative treatments.
Unfortunately, there were also five patients that saw progression of their disease following danazol treatments. These participants together saw worsening pulmonary, aplastic anemia, liver, and bone marrow conditions. Lastly, a patient that came into the study with cancerous bone marrow cells due to their telomere disease saw more deterioration of chromosomes after a year of treatment; however, this increase in deterioration didn’t increase the cancerous bone marrow cells.
Overall, Townsley et al. are correct in stating their findings showed the possibility of danazol being used to treat telomere diseases. The researchers showed significant evidence that danazol can help promote elongation of telomeres. However, there were many variables that brought complications and limitations. The reality is that of 25 starting participants, 10 had to withdraw and 5 saw symptoms of their disease progress despite not experiencing telomere reduction. This shows 60% of participants experienced some negative response.
While danazol has shown to help prevent disease progression, the negative results associated with this treatment contribute to why the FDA and NHLBI haven’t approved this drug for this indication. More results should be evaluated before considering danazol treatments, but this study was a first promising step for hormone therapies’ potential to fight telomere degeneration.
References:
Townsley, D. M., Dumitriu, B., Liu, D., Biancotto, A., Weinstein, B., Chen, C., ... & Yao, J. (2016). Danazol treatment for telomere diseases. New England Journal of Medicine, 374(20), 1922-1931.