Tag: genetics

Times of London Shines Light on HCM

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Just in time for today’s HCM Awareness Day, on Sunday the Times of London ran a feature story about the work that U.K. professor Hugh Watkins and his team are doing to find a cure for HCM using gene therapy.

The story begins with an interview with Massachusetts resident Wendy Borsari, who shared the tale of her family’s extensive and tragic history with HCM.  Over the past several generations, 27 members of Wendy’s family have suffered from HCM, and family members have endured 7 heart transplants and 18 deaths.

On a personal note, Wendy has worked tirelessly for many years to improve things for other HCM patients, and she was integral to the creation of HCMBeat. You can read her guest blog about her daughter Ashlan’s cardiac arrest right here.

Going back to the Times feature, the focus of the story is on the work that a team led by Dr. Hugh Watkins is doing under the name the Cure Heart Project.  The project was funded by a £30 million grant ($36 million) from the British Heart Foundation which the team won last year.   Over the 5 years of the grant, Dr. Watkins and his team are testing multiple gene therapies intended to treat genetic cardiomyopathies. The team plans to have their technology ready for human trials by the end of the study. The hope is that these treatments will stop progression of disease, possibly reverse some of the damage, and if given early enough, the scientists hope that the treatments can prevent the disease from developing at all.

Clinical trials would start on the sickest patients, such as those who are waiting for a heart transplant. Once they demonstrate that the treatments work, they hope to administer the treatment to gene positive patients who have not yet developed the disease with the hope that in these patients, it would be a cure.

With so much work being done around gene therapy for HCM, sooner or later, someone is going to be successful.  We just hope it is sooner rather than later!

HCMBeat has written several previous blog entries describing the work being in hopes of finding a a genetic cure for HCM.  They are linked below.

Gene Therapy – Is a Cure for HCM Around the Corner?

Tenaya Therapeutics Gets Go-Ahead for HCM Gene Therapy Trial

Gene Therapy – Is HCM Cure Possible?

Gene Therapy for HCM

Targeted Gene Therapy for HCM

The Future of HCM Treatment

HCM Genetics Discovery by British Researchers

The Future of HCM Care

CRISPR Eliminates HCM Gene !

Gene Therapy – Is a Cure for HCM Around the Corner?

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Two different papers published in the newest issue of Nature focus on experimental gene therapies to potentially repair the genes that cause hypertrophic cardiomyopathy.  This research even caught the eye of Dr. Eric Topol, a prominent cardiologist at the Scripps Institute whose focus on genetics and digital technologies aims to change the future of medicine.

Researchers in the first study were able to correct pathogenic HCM mutations in an MYH7 gene. This was done both in cardiomyocytes (the cardiac cells which cause the heart to contract) derived from human pluripotent stem cells, as well as in mice with human-like HCM mutations.

The second study used two different genetic therapies to prevent HCM caused by the R403Q mutation in more than 70% of cardiomyocytes carrying the mutation.

The researchers hope that these findings will soon allow scientists to treat patients who carry an HCM gene BEFORE the disease actually develops, thereby interrupting the cycle and preventing the disease

It would be very exciting to see a clinical trial testing this technology. These therapies show great promise for our children and grandchildren.

HCM Genes Common in General Population

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A recent study sought to find how common genetic cardiomyopathies are in the general population. 

By studying United Kingdom Biobank samples from 200,643 people who had undergone complete genetic sequencing, researchers established that genes linked to HCM are found in one out of every 149 people! 

More than half of those identified as having a HCM gene had a mutation in the MYBPC3 gene, making it the most common HCM gene in this sampling.

Gene Therapy – Is HCM Cure Possible?

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A team of international genetic researchers has just won “The Big Beat Challenge” – a grant from the British Heart Foundation of £30 million ($36 million) payable over a 5 years period to study potentially curative gene therapies to treat genetic cardiomyopathies.

Continue reading “Gene Therapy – Is HCM Cure Possible?” →

Scientists Seeking Patient Input: Gene Therapy to Treat Inherited Cardiomyopathies

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A group of scientists working on gene therapy for inherited cardiomyopathies are seeking input from patients about their interest and willingness to participate in gene therapy trials. These researchers hope that treatment with gene therapy will ultimately prove to be a cure for hypertrophic cardiomyopathy as well as other genetic cardiomyopathies.

If you are interested in learning more about gene therapy and are willing to answer a few questions about your willingness to participate in this type of research, watch this video.  Then, fill out this short questionnaire.  It just takes a few minutes and you may help to find a cure for HCM.

Targeted Gene Therapy for HCM

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The expanding field of personalized medicine has not left hypertrophic cardiomyopathy behind. In fact, two companies are currently developing targeted gene therapies for HCM patients. Each therapy targets a separate and distinct HCM gene mutation.

Tenaya Therapeutics, located in the San Francisco area, is developing a therapy called TN-201 which is directed at mutations in the Myosin Binding Protein C3 (MYBPC3) gene. The therapy has shown favorable results in mice.  In May of this year, Tenaya received Orphan Drug Designation from the U.S Food and Drug Administration. An Orphan Drug Designation confers certain tax and economic incentives on companies developing a treatment for rare conditions.

Meanwhile, this week, Lexeo Therapeutics acquired Stelios Therapeutics, a San Diego based company developing a therapy for HCM patients with a mutation in the TNNI3 gene. These TNNI3 patients comprise somewhere between 5% and 7% of all patients with HCM, or approximately 30,000 people.  The underpinnings of this research come from the University of California, San Diego.

HCMBeat will continue following these developments. It is a busy and exciting time in the treatment of HCM!

Identical Twins Show Impact of Behavior and Environment on HCM

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A recent study of identical twins with HCM found significant variation in the expression of hypertrophic cardiomyopathy, even between twins carrying the same HCM-causing genetic mutation. 

This paper concludes that epigenetics (things which influence expression of DNA like behavioral and environmental factors) greatly influence the expression of HCM genetic mutations. 

The researchers studied 11 pairs of twins with HCM. 9 of the twin pairs had known HCM sarcomere mutations while 2 of the pairs had HCM of unknown cause. The siblings were followed for a time frame of between 5 to 14 years.

Researchers compared left ventricular wall thickness, left atrial size and left ventricular ejection fraction. Differences were found in the left ventricular wall thickness of all 11 pairs of twins, while left atrial size was similar in 3 of the 9 twin pairs who carried HCM mutations. Left ventricular ejection fraction was different in 4 of 7 twin pairs. 

The researchers theorize that similarities in left atrial size may be due to impaired ventricular relaxation directly tied to sarcomere dysfunction. In contrast, environmental factors yield more influence over ventricular function.

HCM epigenetics is a field ripe for research. As HCM patients, we hope that it will yield actionable data in the near future.

HCM Genetics Discovery by British Researchers

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A recent discovery by British researchers sheds light on how a type of common genetic mutation – a so called “common variant” – influences the expression of hypertrophic cardiomyopathy caused by mutation(s) in the cardiac sarcomere. 

How do Common Variants Impact Sarcomere Mutations?

This research, funded by the British Heart Foundation and spearheaded by Dr. Hugh Watkins of the University of Oxford, explains why some individuals with a particular sarcomere mutation develop a severe case of HCM, while their family members with the same mutation may develop only mild HCM symptoms or show no signs of the disease at all.  It also may explain why people who lack sarcomere mutations develop the disease.

The researchers compared the DNA of 2,780 people with HCM and 47,486 people without HCM and found that common variants acting in concert with rare sarcomere mutations determine whether a person will develop HCM. 

Common Variant HCM Not Hereditable

In addition, the researchers found that HCM attributable to common variants alone is unlikely to be passed on to future generations. This is good news for the children of HCM patients caused by common variants.

Watch your Blood Pressure

Lastly, this paper found that high diastolic blood pressure was associated with the development of  HCM caused by common variants. Hence, keeping blood pressure under control is something that patients can do to minimize their risk of developing HCM in the future.

A link to the study in Nature Genetics can be found here;
You can access a thorough summary by the British Heart Foundation here;
and you can find a short summary at Medical Xpress here.

2020 AHA/ACC HCM Diagnosis & Treatment Guidelines Released – Updated With New Links

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The highly anticipated 2020 American Heart Association/American College of Cardiology Guidelines for the Diagnosis and Treatment of Patients with Hypertrophic Cardiomyopathy have been released.

This document, drafted with reference to published HCM literature, and with input from a committee of HCM experts with broad expertise, updates the prior version published in 2011.  It contains clinical practice guidelines for the broad spectrum of issues which may confront medical professionals as they approach the diagnosis and treatment of patients and families affected by hypertrophic cardiomyopathy.

Continue reading “2020 AHA/ACC HCM Diagnosis & Treatment Guidelines Released – Updated With New Links” →

Wall Street Journal Highlights Risks in Genetic Testing

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This story in the Wall Street Journal about genetic testing shows the speed of changes in the medical community’s understanding of how and whether certain genes cause hereditary disease.

The article quoted Dr. Jodie Ingles, a geneticist from the University of Sydney in Australia who specializes in HCM and has published a recent article on the subject.  Dr. Ingles said that 22 out of 33 genes comprising a genetic testing panel commonly used to test for HCM had either limited or no evidence of being disease causative.

Continue reading “Wall Street Journal Highlights Risks in Genetic Testing” →