The purpose of this project is to study DNA and its connection to your health. DNA is in your blood, your saliva, and other tissues in your body. DNA is the unique instructions you are born with that tells your body how to work. By looking at DNA, you can learn information about your health, certain traits, and even your ancestral roots. DNA is also called your genetic information. DNA is mostly the same from person to person. But everyone's DNA is slightly different. We are still learning how DNA impacts health. This study will look at the DNA of many different people from many different backgrounds and compare it to information in their health records. The goal is to understand how learning about DNA can help improve health care for individuals, families, and the community.

Participants will provide a sample for DNA sequencing. Sequencing is the process of reading the letters of your DNA. This study may sequence your whole genome. Over time, you may be asked to provide additional samples for research purposes. The research team will collect health information about you from your medical record and may ask you questions about your health using surveys or other data collection method.

The purpose of this project is to study DNA and its connection to your health. DNA is in your blood, your saliva, and other tissues in your body. DNA is the unique instructions you are born with that tells your body how to work. By looking at DNA, you can learn information about your health, certain traits, and even your ancestral roots. DNA is also called your genetic information. DNA is mostly the same from person to person. But everyone's DNA is slightly different. We are still learning how DNA impacts health. This study will look at the DNA of many different people from many different backgrounds and compare it to information in their health records. The goal is to understand how learning about DNA can help improve health care for individuals, families, and the community.

Participants will provide a sample for DNA sequencing. Sequencing is the process of reading the letters of your DNA. This study may sequence your whole genome. Over time, you may be asked to provide additional samples for research purposes. The research team will collect health information about you from your medical record and may ask you questions about your health using surveys or other data collection method.

The purpose of this project is to study DNA and its connection to your health. DNA is in your blood, your saliva, and other tissues in your body. DNA is the unique instructions you are born with that tells your body how to work. By looking at DNA, you can learn information about your health, certain traits, and even your ancestral roots. DNA is also called your genetic information. DNA is mostly the same from person to person. But everyone's DNA is slightly different. We are still learning how DNA impacts health. This study will look at the DNA of many different people from many different backgrounds and compare it to information in their health records. The goal is to understand how learning about DNA can help improve health care for individuals, families, and the community.

Participants will provide a sample for DNA sequencing. Sequencing is the process of reading the letters of your DNA. This study may sequence your whole genome. Over time, you may be asked to provide additional samples for research purposes. The research team will collect health information about you from your medical record and may ask you questions about your health using surveys or other data collection method.

The purpose of this project is to study DNA and its connection to your health. DNA is in your blood, your saliva, and other tissues in your body. DNA is the unique instructions you are born with that tells your body how to work. By looking at DNA, you can learn information about your health, certain traits, and even your ancestral roots. DNA is also called your genetic information. DNA is mostly the same from person to person. But everyone's DNA is slightly different. We are still learning how DNA impacts health. This study will look at the DNA of many different people from many different backgrounds and compare it to information in their health records. The goal is to understand how learning about DNA can help improve health care for individuals, families, and the community.

Participants will provide a sample for DNA sequencing. Sequencing is the process of reading the letters of your DNA. This study may sequence your whole genome. Over time, you may be asked to provide additional samples for research purposes. The research team will collect health information about you from your medical record and may ask you questions about your health using surveys or other data collection method.

This study is seeking participants with arrhythmogenic cardiomyopathy (ACM), also known as arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), due to a genetic abnormality known as a PKP2 variant. ARVD/C is an inherited disease where the muscle tissue in the right ventricle, one of the lower pumping chambers of the heart, dies and is replaced with scar tissue. This causes a weakened heart muscle and disrupts the heart's electrical system which can lead to heart failure and/or fatal heart rhythms. This study is looking at the safety and effectiveness of an investigational medication, meaning it is not yet approved for use by the Food and Drug Administration (FDA). The study medication is a gene therapy called LX-2020, and is designed to add new PKP2 genes to replace the faulty ones so your cells can make the correct PKP2 genes. The study medication is given via an intravenous (IV) line meaning in a vein. Participation in this study involve up to 25 visits including a hospitalization over the course of 1 year with an additional 4 years of follow up afterwards. Study related procedures include a variety of heart testing like electrocardiogram (ECG), echocardiogram, a test that records a tracing of the heart's electrical activity, Echocardiogram, (echo) a test that uses ultrasound to capture moving images of the heart, magnetic resonance imaging (MRI), a test that shows an image of the heart and surrounding structures, sample collection including blood, urine, tissue, nasal mucus, saliva and stool, liver ultrasound, questionnaires, physical exams, and at least a two night stay in the hospital. Medications to suppress (meaning weaken) the immune system, before receiving the LX2020 are also required. Risks associated with gene therapy include an immune response that may cause inflammation in the liver, heart or other organs. It may damage red blood cells, cause a low platelet count or cause the formation of small blood clots. There are also risk related to the study procedures including bleeding associated with the heart biopsy, risks related to drawing blood, risks of radiation, and loss of confidentiality. There is potential benefit and in the future, others with ACM may benefit from the knowledge gained from this study.

This study is for those with Transthyretin (TTR) Amyloidosis with Cardiomyopathy or ATTR-CM. ATTR-CM is a condition where the heart muscle does not pump your blood through your body as it should because of build up of abnormal protein between the muscle fibers in your heart. The specific protein is called transthyretin amyloid (TTR). The study involves an investigational drug called NTLA-2001. Investigational means it is not approved for commercial sale or use by the Food and Drug Administration. This study is a randomized study meaning participants will be assigned by chance to receive NTLA-2001 or placebo. A placebo looks like the investigational drug but contains no active ingredient. In this study, two out of three participants are assigned to receive NTLA-2001 and one out of three will receive placebo. NTLA-2001 or placebo are given by intravenous (IV) infusion meaning in your vein.

NTLA-2001 consists of a gene editing system which can "knockout" the TTR gene and permanently change the DNA (deoxyribonucleic acid, which contains information that determines parts in traits such as eye color or height, that are passed on from parent to child) so the gene stops making the TTR protein.

This study will last at least 18 months and include up to 17 visits. Study related procedures include physical exams, blood work including genetic testing, eye exam, hall walk test, electrocardiograms (ECGs), echocardiogram (echo) and vitamin A supplement. Study risks include infusion related risks like headache, fever, chills, or increased liver enzymes. Other study related risks include genetic risks, loss of confidentiality and unknown risks.

This study is an open label extension study for those who participated in the ION 682884-CS2 clinical trial for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). ATTR-CM is a disease caused by change in a protein called transthyretin (TTR) which can result in a build up of this protein in parts of the body including the heart. This build up is called an amyloid deposit, and when this occurs in the heart it can lead to a condition called cardiomyopathy. This study involves the medication eplontersen, which is considered investigational meaning it is not approved for commercial use by the Food and Drug Administration (FDA). Eplontersen is aimed at preventing production of the TTR protein to slow or reverse disease progression. Eplontersen is given as an injection under the skin in the upper arm, stomach or thigh. This study will last about 3 1/2 years and include 16 clinic visits. Study procedures include physical exams, blood work, questionnaires, hall walk tests, electrocardiograms (tracing of the heart's electrical activity), echocardiogram (ultrasound test of the heart) and taking a Vitamin A supplement.

The purpose of this study is to evaluate the safety and effectiveness of acoramidis (AG-10) and determine if it can help people with the genetic TTR variant that can cause ATTR-CM. The sponsor (Eidos) is conducting a research study to see if the study medicine will help in slowing the development and/or progression of a rare disease called Symptomatic Transthyretin Amyloid Cardiomyopathy (ATTR-CM). AG-10 is an investigational drug. "Investigational" means that AG-10 is not yet approved for use in any settings outside of clinical research studies like this one and is considered experimental. Cardiomyopathy is a disease of the heart muscle that makes it harder for the heart to pump blood to the rest of the body. AG-10 has been shown to reduce the level of TTR in the blood of animals and healthy volunteers tested to date. Reducing the amount of TTR in your blood may reduce the amount of amyloid deposits in your body and may keep your cardiomyopathy from getting worse over time.

If you meet the requirements and agree to participate in this study, you will go through a 2 part screening period and if approved you will begin treatment. You will be randomized, like flipping a coin, to drug or placebo and take two pills once every day for 60 months.
Your participation in this study will last up to 60 month and will consist of clinic visits and follow up visits at home via the telephone. Some tests requires of you will include an echo, ECG, cardioradionuclide scans (scans that use radioactive agents to look at images of the heart like a PET scan), MRIs, blood tests, nerve conduction test, urine samples, and skin biopsies.

This study is enrolling participants with symptomatic ATTR-CM (transthyretin amyloidosis cardiomyopathy). ATTR-CM is a rare and serious disease that occurs when a protein in the blood called transthyretin (TTR) builds up throughout the body, including in the heart and nerves. When the abnormal protein, known as amyloid, deposits in the heart, the heart muscle thickens and stiffens, causing the heart to fail. This research study is designed to test whether the medication nucresiran is safe and helps people with ATTR-CM, in comparison to the effects of placebo.

Nucresiran is considered investigational, meaning it is not currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of ATTR-CM. Nucresiran is a TTR silencer. It is like a "quiet button" that turns down the amount of the disease-causing protein that is made. Because there is less TTR, there may be less buildup in the heart and other organs over time.

This is a randomized study meaning once eligibility is confirmed, participants will be assigned by chance, like drawing straws, to either receive nucresiran or placebo. You will have a 2 out of 3 chance of being assigned to nucresiran and a 1 out of 3 chance of being assigned placebo. Placebo is a substance that looks like the actual medication and is given the same way but contains no active substance. The study drug, which can be either nucresiran or placebo, will be given as an injection under the skin in the abdomen (avoiding the area around the navel), thigh, or the side or back of the upper arms. Neither the participants nor the study doctor will know who is assigned to nucresiran or placebo but this information can be made available if need be.

Participation in this study is expected to last for 5-8 years, Study related procedures include physical exams, vital signs, echocardiograms (ultrasound test of the heart), electrocardiograms, (ECG, a tracing of the heart's electrical activity), blood work, urine samples and questionnaires. Participants will also take Vitamin A daily. Study related risks include risks related to the study drug including injection site reactions, abnormal liver function or an allergic reaction. There may be risks related to study procedures including loss of confidentiality. There may not be any direct benefit, but the information learned may benefit others with ATTR-CM in the future.

The GRIT-PKP2 study will evaluate the long-term safety and tolerability of LX2020 gene therapy for subjects with PKP2-ACM who have previously received an investigational study medication called LX2020. PKP2-ACM is an inherited heart condition which can cause heart muscle and electrical damage. Investigational means it is not approved for use by the Food and Drug Administration (FDA). There is no investigational treatment being administered in this study. The overall study duration is 4 years. The study consists of 7 visits: a rollover visit, an outpatient monitoring period, (5 visits, 18 months to 48 months after LX2020 administration in Study LX2020-01), and an end-of-study visit. Procedures and activities that subjects will undergo are: quality of life questionnaires, ECG, MRI, ultrasound, ECHO, collection of samples, remote cardiac monitoring, and collection of vital signs.