Dr. Stephen Heitner, together with his colleagues at Oregon Health & Sciences University, published an article last week in the European Journal of Heart Failure which gives a glimpse into the treatment of hypertrophic cardiomyopathy (HCM) in the future. Although recent publications have stated that the majority of HCM patients today have a favorable prognosis when receiving appropriate treatment, a heavy disease burden continues to be placed upon patients. Hence, better and more effective treatments for HCM are still needed in order to lessen this burden.
The article provides a very thorough overview of both current and future HCM therapies and divides them into a few different categories listed below.
- Potential for New Drugs: No drugs have been specifically approved for the treatment of HCM by the Federal Drug Administration. Up until now, all drugs used to treat HCM patients (with the limited exception of propanolol) have been off-label uses. However, this is likely to soon change. Current trials of myosin modulators like MyoKardia’s mavacamten and Cytokinetic’s CK-274 have so far yielded promising results and have the potential to change the treatment paradigm for HCM.
- Subcutaneous ICDs (S-ICDs) are sometimes a reasonable choice for preventing sudden cardiac death in HCM patients when pacing is not required. This allows the patient to avoid risks associated with lead malfunction.
Septal Reduction Therapy:
Gene Editing and Silencing:
- Pre-implantation Genetic Diagnosis (PGD): Current medical technology allows patients with known HCM gene(s) to use pre-implantation genetic diagnosis of embryos together with in-vitro fertilization in order to avoid passing along the HCM gene to the embryo. The future may soon see these methods being used in tandem with gene repair, using CRISPR/Cas9 in order to edit out the errant gene and replace it with a normal one.
- Gene Silencing: Allele specific gene silencing may also prove to be a technique used in the future for preventing HCM. This technique involves the introduction of an adenovirus containing a short RNA segment designed to turn off the HCM gene.
In conclusion, this paper highlights the many things that HCM patients have to be optimistic about going forward. Perhaps one day soon one of these methods will lead to the ultimate goal – a cure!
Cytokinetics today announced that its Phase 2 double-blind study of its experimental drug CK-274 entitled “REDWOOD-HCM” (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM (hypertrophic cardiomyopathy) has begun enrollment. The trial will enroll patients with symptomatic, obstructive HCM.
CK-274 is a next-generation cardiac myosin inhibitor which the company hopes will prove to be beneficial for the treatment of hypertrophic cardiomyopathy (HCM).
There are currently two companies in clinical trials for HCM: Cytokinetics and MyoKardia. You can read more about their efforts here and here.
A recent study in Europe found that HCM patients’ risk of death continues to exceed the risk in the general population.
This study looked at 4893 patients with hypertrophic cardiomyopathy treated at 7 different European HCM centers between 1980 and 2013. Although the statistics improved for those who were treated more recently, this study makes it clear that there is still much room for improvement in risk stratification and treatment for patients with HCM.
This Medscape article highlights the extraordinary efforts of Dr. Harry Lever, Director of the Cleveland Clinic’s Hypertrophic Cardiomyopathy Center, in educating patients and physicians alike about quality issues with generic drugs. Dr. Lever has been instrumental in publicizing the fact that generic drugs are NOT always the same as their name brand counterparts, and that foreign generics are not put through the same level of scrutiny as drugs in the U.S.
Continue reading “Dr. Harry Lever Speaks Out About Problems With Generic Drugs”
A recent study by Canadian researchers published in the American Heart Association journal Circulation found a much lower incidence of HCM related sudden death than expected. The study included deaths in individuals that occurred between the ages of 10 and 45 in the Canadian province of Ontario between 2005 and 2016. According to lead author Dr. Paul Dorian of the University of Toronto, the expectation was that 1 incident of sudden cardiac death would be identified in every 100 to 200 people who had HCM. Instead, researchers found that the likelihood of sudden death of HCM patients was instead only about 1 in 3,000 people/year.
The study also found that found 7 in 10 HCM-related sudden deaths occurred in people not previously diagnosed with the condition. Men had more than 5 times the risk of sudden cardiac death than women, and most deaths occurred during rest or light activity: only about 17% happened during or immediately after exercise.
As a result of the study, according to Dr. Dorian, “our findings allow us to lower the temperature on our degree of worry about the condition.”
Another clinical take away from the study, according to the researchers, is that current exercise guidelines for HCM patients may be too restrictive.
Recently, Cynthia Waldman of HCMBeat corresponded with Dr. Srihari S. Naidu of Westchester Medical Center the second edition of an HCM textbook he recently edited, as well as about medical education surrounding hypertrophic cardiomyopathy in general. What follows is a transcript of their correspondence (which has been slightly edited for readability).
Continue reading “Dr. Srihari Naidu Talks About HCM Medical Education”
Two San Francisco based companies are now conducting clinical trials for three drugs specifically targeting HCM.
Continue reading “2 Companies Testing Drugs for HCM”
A recent study by doctors at Toronto’s Hospital for Sick Children suggests that current screening guidelines for children from HCM families are inadequate and should instead recommend earlier screening exams. In the U.S., screening begins at age 12 pursuant to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. In Europe, screening begins at age 10 pursuant to the European Society of Cardiology (ESC) guidelines.
Continue reading “Should Children from HCM Families be Screened Earlier?”
A group of scientists led by Stanford University’s Dr. James Spudich, working together with researchers from the University of California-Santa Barbara, the University of Washington and the Institut Curie in Paris, has recently been awarded a $10 million grant by the National Institute of General Medical Sciences to develop novel treatments for hypertrophic cardiomyopathy (HCM).
The researchers hope that the added resources from this grant will help them find ways to correct pathological heart protein changes they believe to be at the root of HCM. The team then plans to partner with pharmaceutical companies to develop more personalized approaches to HCM treatment.
Dr. Spudich has long been involved in HCM research and has been a founder of two separate companies which are currently engaged in drug trials for potential HCM treatments: MyoKardia and Cytokinetics.
A story about Dr. Spudich and the inspiration for his work was featured in this recent post on HCMBeat.