Advancing Genetic Therapy and Personalized Medicine

Considering 75% of rare disorders are genetic (caused by a mistake or change in the genes which can run in families), finding a center that specializes in genetic rare disease and the latest gene therapies is an important find.

Gene therapy is a new area of medicine that aims to treat or prevent diseases by changing or fixing genes in a person’s cells. It works by adding genetic material to cells to replace genes that are missing or not working properly, or to give the cells new abilities.

After decades of research, which included triumphs as well as setbacks, the first gene therapies were approved by the FDA for cancer in 2017 and for a rare disease, spinal muscular atrophy, in 2019.

The Department of Genetic Medicine has a history of accomplishments in the field of gene therapy. Over the last 25 years, the Belfer Gene Therapy Core Facility and the Department of Genetic Medicine at Weill Cornell have had over 200 research technicians contribute to the science in numerous ways. They authored peer-reviewed publications, presented at national meetings, and won awards for their work in gene therapy.

The department chair, Ronald G Crystal, is the first physician to administer a genetically modified treatment to a human patient in an approved clinical trial. Continuing to be pioneers in the field, the Genetic Medicine Program is developing new methods and translating research on complex diseases to bring to patients in the clinic. Doctors use information about a person’s genes to better understand diseases, choose the right medicine and dose, plan treatments, and help prevent future health problems. They may also use medical images, lab results, and other information about the patient and their disease to create the best treatment plan.

Areas of Research

• Friedreich’s ataxia
• Alzheimer’s disease
• Cocaine addiction
• Alpha-1 antitrypsin deficiency
• Eosinophilia/Eosinophilic esophagitis
• Angiogenesis for heart disease, fat transplant, and surgical wound healing

Weill Cornell’s gene therapy and stem cell researchers have carried out human trials for cystic fibrosis, cardiac ischemia, cancer and central nervous system disorders, and were one of earliest investigators of gene therapy in humans.

Current clinical trials at Weill Cornell:

Study focused on cardiac disease in FA

Friedreich’s Ataxia (FA) is a genetic disease that causes nervous system damage, which leads to impaired muscle coordination over time, and is also associated with cardiac disease, specifically cardiomyopathy (diseases that affect the heart muscle, myocardium). It causes the heart muscle to become enlarged, thick, or stiff, making it harder for the heart to pump blood effectively to the rest of the body.  While many symptoms of FA can impact patients’ lives, cardiac disease is the major cause of death, responsible for 60 to 65% of deaths in those with FA. 

Gene Therapy for the Cardiomyopathy of Friedreich’s Ataxia

FA is caused by a mutation in the gene that codes for the protein frataxin (FXN). Frataxin is critical for proper energy production within cells. Those with FA produce reduced levels of this protein, and wiithout enough FXN, there is not enough energy for the heart to function normally.

In this study, an investigational gene therapy is given as a single, intravenous administration of a dose that delivers the normal FXN gene to the heart. It is hoped the gene therapy will help cause the production of normal amounts of frataxin, restoring the function of the heart cells, and limiting the effects of cardiac disease. The goal of this phase I study is to assess the safety and initial estimates of efficacy of the gene therapy in treating FA-associated heart disease.

To participate you must have a definite diagnosis of FA -- detailed eligibility to be discussed with the study team.

Study duration: 5 years

Age: 12-50 years old

Compensation: You will receive reimbursement for travel expenses, accommodations, and meals associated with participating in the trial

Study focused on alpha 1-antitrypsin deficiency

Alpha 1-antitrypsin deficiency is a genetically inherited condition that affects the lungs and/or the liver. It is passed on from parents to their children through genes. It is a progressive condition, which means it may worsen over time. AAT normally protects the lung from damage. In this condition, the AAT protein is abnormal and cannot be released from the liver to protect the lungs. This can result in chronic obstructive pulmonary disease (COPD). It can lead to serious lung and/or liver disease.

For the current therapy, symptoms can be treated with standard medical therapy (such as bronchodilators), augmentation therapy (giving patients the AAT protein by intravenous infusion, usually every week or every month) and/or behavioral measures (such as smoking cessation).

 Gene Therapy for Alpha 1-Antitrypsin Deficiency

In this study, an investigational gene therapy is given as a single, intravenous administration of a dose that delivers the normal SERPINA1 gene. It is hoped the gene therapy will help cause the production of normal amounts of AAT protein, which if safe and efficacious, and will protect the lung on a persistent basis.. The goal of this phase I study is to assess the safety and initial estimates of efficacy of the gene therapy in treating alpha 1-antitrypsin deficiency.

To participate you must have a definite diagnosis of alpha 1-antitrypsin deficiency -- detailed eligibility to be discussed with the study team

Study duration: 5 years

Age: 18-70 years old

Compensation: you will receive the reimbursement of your travel expenses, accommodations and meals associated with participating in the trial.

Learn More About the Department of Genetic Medicine

• Website: geneticmedicine.weill.cornell.edu
• Instagram: @wcmgeneticmedicine
• LinkedIn: Weill Cornell Medicine Department of Genetic Medicine

Clinical Trial Listings

• Friedreich’s ataxia trial on ClinicalTrials.gov (NCT05302271)
• Alpha-1 antitrypsin deficiency trial on ClinicalTrials.gov (NCT06996756)