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.
NEWS FROM MYOKARDIA
MyoKardia recently announced a new clinical trial of its drug, mavacamten (formerly known as MYK-461) which will compare the clinical results of mavacamten with septal reduction therapies currently used in clinical practice, i.e. the open heart surgical procedure known as septal myectomy and the catheter based procedure known as alcohol septal ablation.
The study will be run by the Cleveland Clinic with Dr. Milind Desai serving as principal investigator. MyoKardia expect to begin enrolling patients in early 2020.
Read the press release here.
NEWS FROM CYTOKINETICS:
Cytokinetics released positive data from its Phase 1 study of the drug currently known as CK-274 in a poster session at the HFSA 23rd Annual Scientific Meeting in Philadelphia. The study found that CK-274 was safe and well tolerated, while no serious adverse events or negative changes to vital signs, ECGs or laboratory tests were observed.
The company will now be moving into a Phase 2 clinical trial of CK-274 in patients with obstructive hypertrophic cardiomyopathy, expected to begin in late 2019.
Read their press release here.
DISCLOSURES: HCMBEAT HAS RECEIVED PAST UNRESTRICTED EDUCATIONAL GRANTS FROM MYOKARDIA. ADDITIONALLY, CYNTHIA BURSTEIN WALDMAN OF HCMBEAT SERVES AS A PATIENT ADVISOR ON THE STEERING COMMITTEE FOR MYOKARDIA’S EXPLORER TRIAL.
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 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.
According to a limited study recently published in Nature, researchers were able to detect obstructive HCM (HOCM) using a noninvasive optical sensor contained in many commercial smartwatches.
How the Technology Works
These watches used photoplethysmography, a noninvasive optical method used to detect blood volume changes in the microvascular bed at the skin surface. The same technology is used in clinical pulse oximeters and is now widely incorporated in commercial smartwatches that have heart rate detection.
Continue reading “Can a Smartwatch Detect HOCM?”
When Stanford biochemist Jim Spudich settled down in bed with a book recommended by his wife, he had no idea that the book would inspire one of the biggest discoveries of his career. Spudich drifted off to sleep while reading The Haunted Mesa, a science fiction novel by Louis L’Amour. His scientific discovery was based on an image he saw in his dreams when the image of a mesa morphed into a myosin molecule.
Continue reading “How a Louis L’Amour Book about the Southwest Inspired a HCM Discovery”
MyoKardia is collaborating with 23andMe, a genetic testing company which provides ancestry and health information directly to consumers, to create an online patient community intended to advance research efforts related to hypertrophic cardiomyopathy. The companies plan to allow 23andMe customers access to the latest information about HCM, as well as the opportunity to participate in research.
The companies will use a custom designed survey to collect baseline and follow-up data from HCM patients. They are hopeful that this collaboration will yield unique insights into HCM.
Research findings gained through the collaboration will be shared with HCM patients through the 23andMe platform. Currently more than 6,000 HCM patients are customers of 23andMe
More details of the collaboration can be found:
Press release from MyoKardia and 23andMe
DISCLOSURES: HCMBeat has received unrestricted educational grants from MyoKardia. Additionally, Cynthia Burstein Waldman of HCMBeat serves as a Patient Advisor on the Steering Committee for MyoKardia’s Explorer trial.