Alpha-1 antitrypsin (AAT) deficiency is a condition in which the body does not make enough of AAT, a protein that protects the lungs and liver from damage. This condition is inherited, meaning you get the faulty gene from one or both of your parents.

The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of oral administration of BMN 349 in adult participants with the PiZZ genotype (also defined as having a severe deficiency or AAT ≤ 60mg/dL) or PiMZ genotype with metabolic dysfunction-associated steatohepatitis (MASH). Participants will receive an oral single dose of BMN 349 (250 mg), a medication designed to assist Z-alpha-1 antitrypsin to get out of the liver cell. The study drug BMN 349 has not been approved by the Federal Drug Administration (FDA).

This is a phase 1 study in which participants will get a single pill dose of drug or placebo to measure the amount of alpha-1 that gets out of the liver cells and into the bloodstream. Study details include:
• Study duration: up to 78 days
• Treatment duration: 1 day (single dose).
• Observations: The study will collect data on medical history, physical examination, vital signs, electrocardiogram readings, clinical laboratory parameters, pulmonary function tests, and drug distribution.
• Visit frequency: The Screening Visit, dosing, and post dosing evaluations will be conducted at MUSC on 3 consecutive days. Visits at days 8 and 36 days will occur at study site. Other procedures/assessments may be performed at the study site or at home by a healthcare professional and/or by telemedicine.

We are interested in seeing which biomarkers are involved in the pathophysiological pathways of vestibular migraine and Meniere's disease. To this end, we will have eligible patients undergo peripheral blood draws to establish a biobank. The blood samples collected will undergo in vitro testing to determine the cytokine profiles of the immune cells and will also undergo genetic testing. Data and samples collected will be used for future studies as well.

The purpose of this research is to assess the emotional impact on mothers of children with mitochondrial disease (MD). This study plans to compare survey responses between mothers of children with MD caused by mitochondrial DNA (mtDNA) variants, which are exclusively maternally inherited, and nuclear DNA variants (nDNA), which can be inherited from either parent or new in the individual (de novo). This survey also plans to assess the impact on future reproductive decisions due to the fact that reliable preimplantation genetic testing (PGT) for mtDNA variants is lacking and the transmission of mtDNA variants from mother to child is hard to predict.

This study is evaluating the safety and effectiveness of the experimental treatment named AB-1002. The purpose of this study is to look at the safety and feasibility of delivery of adeno-associated virus (AAV) through the coronary arteries into the heart in participants with heart failure and non-ischemic cardiomyopathy. An experimental treatment is another option for care for your disease that is still being tested and is not yet approved by the Food and Drug Administration (FDA).

Participation in this study is expected to last one year and include up to 18 visits. Study related procedures include the following heart related testing: study drug infusion, electrocardiograms (ECG), a test to show the heart's electrical activity, echocardiogram (Echo), a test that uses ultrasound to capture moving images of the heart, cardiopulmonary stress test, sample collection including blood, urine, tissue, nasal mucus, saliva, semen, and stool, questionnaires, physical exams, and at least an overnight stay in the hospital. You will also need to take medications to suppress your immune system.

There are risks associated with this study. Risks associated with gene therapy include an immune response that may cause inflammation in the liver, heart or other organs. It may damage your red blood cells, cause a low platelet count or cause the formation of small blood clots. There are also risks 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 may be no benefit to you but knowledge gained from this study may benefit others with heart failure and non-ischemic cardiomyopathy in the future.

Phenylketonuria (PKU) is an autosomal recessive inborn error of L-phenylalanine (L-Phe) metabolism which is caused by deleterious variants in the gene coding for the phenylalanine hydroxylase (PAH) enzyme. The PAH enzyme catalyses the conversion of phenylalanine (Phe) to tyrosine (Tyr), a precursor of several neurotransmitters, hormones, skin, hair, and eye pigments. Elevated concentration of Phe and secondary metabolites and lower Tyr concentration in blood and in brain cause degenerative neuropathology, neurological symptoms, and intellectual deficits, together with poorly or non-pigmented skin and hair, and musty odor which are characteristic in untreated patients with PKU (1, 2).
This Phase 1/Phase 2 study is designed to assess the safety and efficacy of escalating doses of SAR444836 treatment in participants with PKU. The data collected will help to evaluate whether this adeno-associated virus (AAV) vector which delivers the functional human PAH gene into hepatocytes is effective in the treatment of PKU disease. The expression of PAH gene in hepatocytes is expected to provide steady low plasma levels of Phe similar to those observed in healthy individuals, preventing marked fluctuations caused by normal dietary protein intake.
The study is divided into 2 parts including a dose escalation phase (Stage 1A) and a dose expansion phase (Stage 1B).

Tetra Discovery Partners, Inc. has two studies that are recruiting males aged 9 to 45 to participate in a treatment clinical trial for Fragile X Syndrome. The treatment, called BPN14770, is a phosphodiesterase inhibitor that has the potential to address cognitive and neurological impairment in those with Fragile X Syndrome.

BPN14770-CNS-301 is a clinical trial for males aged 18 to 45 with Fragile X Syndrome. It is double-blind, meaning that neither the study doctor nor the enrolled participants know whether or not they are receiving study drug or placebo. A placebo is an inactive material that looks like the study drug, but does not contain any active study drug.

The main goals of this study are to learn how well the study drug works and how safe the study drug is compared with placebo.

After completing the double-blind study, participants have the opportunity to enroll in the open-label extension of this clinical trial, called BPN14770-CNS-302; "open-label" means that the study doctor and participants are all aware that participants are definitely getting the study medication.

This study is designed to learn about the safety and effectiveness of a new gene therapy called KB408 for Alpha-1 Antitrypsin Deficiency (AATD). AATD is an inherited condition in which a person has low blood levels of a protein known as alpha-1 protease inhibitor (called Alpha1-PI). AATD causes an increased risk of chronic obstructive pulmonary disease (COPD) in the form of emphysema (long term lung disease) and, less frequently, other diseases.
KB408 delivers copies of the genes that produce AAT to the lungs and is given by inhaling a mist (called nebulization). The genes are carried and delivered by a modified herpes simplex virus type 1 (HSV-1). This virus is not harmful and simply acts as a vehicle to deliver the genes to the lungs. The genes that are delivered by KB408 do not change a person's own DNA. This is an open-label study, meaning that the participants, the study doctor, and the sponsor all know that the participants are receiving KB408. KB408 is an investigational product, meaning it is not approved for commercial use by the FDA.
Eligible participants will receive one of three doses of KB408. Participants will have a screening visit first to make sure that they are able to participate in the study. After the screening visit, participants will need to return to the study center 6 more times over 2 months. At the second visit, participants will receive the study drug. Each visit will take between 2 and 6 hours to complete. Study procedures include medical history collection, vitals, physical exam, ECG, spirometry and DLCO, urine cotinine test, blood work, cheek swab, sputum sample, and bronchoscopy (only for participants in cohorts 3a and 3b).
Possible side effects of KB408 include temporary increases in certain cell types in the lungs and temporary increases in the breathing rate after dosing. Since this is the first time that KB408 has been given to humans, it is possible that participants may have an immune reaction to the study drug. There is also a risk with genetic testing and a risk to confidentiality. Participants may not receive any personal benefit from being in this study. There is no guarantee that the Study Drug will help. The information that is collected from the study may help other people in the future.

This is an OLE study for subjects completing from one of two double-blind clinical
trials. Subjects must have completed the Week 13 visit from one of these two parent
clinical trials to be eligible for this OLE.

Over 2400 people who have sickle cell disease and are between the ages of 15 and 45 have been enrolled into the National Registry (SCDIC-I) of patients with Sickle Cell Disease (SCD). A rich resource of natural history data, the SCDIC-I Registry has longitudinal data collected yearly since 2016 from patient surveys (e.g. self reported pain incidences, sleep, barriers to care, experiences during and after pregnancy), medical record abstraction (e.g. medications, transfusion history, co-morbidities) and laboratory results. The 150 patients (or 1200 among the 8 sites) will be selected from both MUSC adult and pediatric SCD clinics starting at 12 years of age; those not previously enrolled in the SCDIC National Registry will be offered the possibility to enroll in SCDIC-II.
We will look at the following:
1- Compare the effect of new SCD medications – crizanlizumab, voxelotor, and L-glutamine – on clinical outcomes in individuals with SCD.
2 - Identify genetic and genomic predictors of response to crizanlizumab, voxelotor, and L-glutamine
3 - Integrate study data into the CureSCi metadata catalog (MDC) to enhance future cross-study analyses.

This project is an extension of the CDC-funded FORWARD (Fragile X Online Registry With Accessible Research Database) study. From its inception in 2010, the goal of the FORWARD study has been to characterize the natural history of fragile X syndrome (FXS). This current extension project is known as FORWARD-MARCH (Multiple Assessments for Research CHaracterization) because it will include multiple assessments to characterize behavioral, adaptive, and cognitive function in greater depth and thereby further improve understanding of the natural history of FXS. FORWARD-MARCH continues the mission of FORWARD to better understand the natural history of FXS in order to improve the lives of children and adolescents with FXS and the lives of their families. FORWARD-MARCH will also better define trajectories of development in FXS that will be useful in understanding the long-term effects of an intervention relative to the natural history of FXS.

FORWARD-MARCH builds upon the foundation of the FORWARD study. The FORWARD study included 24 participating FXS specialty clinics throughout the US that are members of the FXCRC (Fragile X Clinical & Research Consortium). The FORWARD study worked closely with the Centers for Disease Control and Prevention (CDC), the National Fragile X Foundation (NFXF), and other stakeholders in the FXS community. FORWARD-MARCH will also involve a contractor, Chickasaw Nation Industries (CNI), funded through a contract with the CDC. CNI will assist in data collection and management.

Between September 2022 and August 2026, FORWARD-MARCH expects to enroll at least 600 individuals with fragile X syndrome who were born between 2003-2017. The majority of these individuals will already be FORWARD study participants, enabling researchers to conduct longitudinal analyses incorporating previously collected data. Cognitive, behavioral, and adaptive function will be assessed using parent or caregiver-completed surveys and in-person clinical assessments. After completion of data collection, deidentified data will be securely maintained at CDC and will be an important long-term resource for analyses of the natural history of FXS.

Previous phases of the FORWARD study, conducted between 2012 and 2022, have received IRB review and approval by the institutions of each participating clinic. These previous phases of the study did not require review by a CDC IRB, as CDC had no participant contact and did not have access to personal identifying information (PII). The extension of the FORWARD study covered in this protocol (FORWARD-MARCH, 2022-2026) will continue to be reviewed and approved by the institutions of each participating clinic conducting data collection. However, review and approval are also being sought from the CDC IRB because PII will be maintained on CDC servers and because CDC's contractor, CNI, will regularly have access to PII and interact directly with study participants. A reliance agreement allowing CNI to rely on CDC's IRB is being developed and will be executed before data collection is begun. To clarify which aspects of the protocol involve CDC and CNI staff (rather than just clinic staff), sections 3,4 and 5 of this protocol document each end with a subsection that specifically focuses on the role of CDC and CNI staff.