PodMed TT – RNA-Targeted Drugs for Treating Genetic Diseases

Is interfering with RNA a practical approach to managing a disease of mutant proteins? Two New England Journal of Medicine studies Rick and I discuss on PodMed TT this week conclude the answer is yes. That’s for 60 percent or so of folks with the autosomal-dominant disease transthyretin amyloidosis, where aberrant proteins accumulate in the heart and nerves, resulting in death in two to 15 years.

One study took the approach of small interfering RNAs, which target messenger RNA, administered intravenously. The other study used an antisense oligonucleotide to inhibit protein production and was administered subcutaneously. A neuropathy progression instrument and patient-assessed quality of life instrument were used as outcome measures.

The result: only 60 percent of patients responded to treatment. Why did only 60 percent of patients respond to an intervention to a known defect that is so well characterized? I opine that perhaps there’s more to it than simple autosomal-dominant genetics, while Rick speculates that many things remain unknown: best dose, best regimen, or perhaps a combination of these two drugs. In any case, we agree that we’ll be seeing more of RNA-targeted drugs in the future, as the strategy seems much simpler than trying to correct a genetic defect.

Other topics this week include HPV testing versus pap smears and subsequent development of cervical cancer, and use of implantable cardiac defibrillators after a Department of Justice investigation in JAMA; and a look at bleeding risk of DOACs in comparison to warfarin in The BMJ.

Until next week, y’all listen up and make healthy choices.