Gene Therapy for Inherited Metabolic Disorders Program
The Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program at Children’s Hospital of Philadelphia was created by a trailblazing group of researchers and clinicians dedicated to treating inborn errors of metabolism. Inborn errors of metabolism, or “IEMs” refer to a group of disorders (or diseases) that affect metabolic pathways in the body.
Metabolic pathways are like intricate roadmaps guiding the flow of energy and raw materials through your body, ensuring that you have the energy to move, think, grow and repair. They're the behind-the-scenes processes that keep the machinery of your body running smoothly. There are more than 1,000 IEMs and each affects the body differently.
There are currently no cures for IEMs – only therapies to help manage them.
How we serve you
Our program was created to find new ways to treat – and potentially cure IEMs. Our passionate group of researchers have been investigating gene therapies to treat IEMs for more than a decade.
We know that an IEM diagnosis can be stressful – for both you and your child. Our team is uniquely positioned to help you through it all. We can evaluate your child, provide a second opinion, and lay out a course of action. We can walk you through the different gene therapy options that are available today, including clinical trials.
Conditions we treat
Inborn errors of metabolism (IEMs) are devastating, rare genetic disorders that affect organs – and how they work together – within a child’s body. There are more than 1,000 unique IEMs, each affecting children with these disorders differently.
Typically, IEMs affect multiple organs and can be life-limiting or life-threatening. There are no known cures for IEMs, but supportive therapies can lessen symptoms in some cases. Scientists are researching additional molecular therapies that could offer more support for many children with IEMs – and potentially offer cures.
At CHOP, we offer evaluation for children with:
- Inborn errors of metabolism
- Phenylketonuria (PKU)
- Medium chain acyl-CoA dehydrogenase deficiency (MCAD)
- Multiple sulfatase deficiency (MSD)
We also evaluate children with less common conditions that fall into five general categories:
- Amino acid disorders that affect the body’s ability to use proteins from food for growth, energy and repair including: tyrosinemia, MSUD (maple syrup urine disease), cystinosis CBS deficiency (homocystinuria).
- Organic acidemia class of IEMs, characterized by accumulation of abnormal – and usually toxic – organic acid metabolites and increased waste of organic acids in urine: MMA (methylmalonic acidemia) and PA (propionic acidemia)
- Fatty acid oxidation defects, IEMs caused by disruption of mitochondrial β-oxidation or the fatty acid transport: AACD deficiency (aromatic L-amino acid decarboxylase deficiency), and GSD 1 (glycogen storage disease type 1).
- Urea cycle disorder, an IEM that causes ammonia to build up in the blood, which is toxic to the body and can affect the brain and organ function: OTC deficiency.
- Lysosomal storage disorders, which are characterized by the accumulation of extra layers in the cells of various organs due to defective lysosome function, and include:
- Pompe disease
- Danon disease
- Sandhoff disease
- Tay-Sachs disease
- GM1 gangliosidosis
- Fabry disease
- Gaucher disease
- CLN2 (neuronal ceroid lipofuscinosis type 2)
- CLN3 (neuronal ceroid lipofuscinosis type 3)
- CLN5 (neuronal ceroid lipofuscinosis type 5)
- CLN6 (neuronal ceroid lipofuscinosis type 6)
- CLN7 (neuronal ceroid lipofuscinosis type 7)
- MPSI (mucopolysaccharidosis type I)
- MPSII (mucopolysaccharidosis type II), also known as Hunter syndrome
- Sanfilippo syndrome (also known as MPSIIIA)
- MPSIIIB (mucopolysaccharidosis type IIIB)
- Krabbe disease
- MLD (metachromatic leukodystrophy)
- Morquio syndrome (mucopolysaccharidosis type IV)
- Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI)
- Lysosomal acid lipase deficiency
- Niemann-Pick disease
At CHOP, our Gene Therapy for Inherited Metabolic Disorders Program is studying how we can better treat – or even cure – diseases by targeting specific genes. There are two main types of gene therapy: ex vivo and in vivo. Ex vivo gene therapy means that cells are removed from the body, modified in our lab, and then put back into the body. In vivo gene therapy means something is delivered directly to the cells, telling the genes to do something differently. CHOP is a leader in developing and administering both types of gene therapy.
Three current research projects include:
- A natural history study of MSD (multiple sulfatase deficiency) in the hopes of developing an ex vivo gene therapy
- Developing liver-direct genome base editing therapy for PKU (phenylketonuria)
- Developing liver-direct prime editing therapy for MCAD (medium chain acyl-COA dehydrogenase deficiency)
To view active gene therapy clinical research trials at CHOP, visit Study Finder.
Why choose us for IEMs
Metabolic physicians and subspecialists at CHOP are among the world’s most well-respected leaders on inborn errors of metabolism (IEMs). Two of our physicians are leading more than 10 observational and interventional trials on IEMs, and a third leads one of the largest and most prestigious IEM training programs in the world.
We offer a robust translational gene editing program that is supported by funding from the U.S. National Institutes of Health. In addition, CHOP’s Gene Therapy for Inherited Metabolic Disorders Program leads both pre-clinical and clinical trial readiness studies for MSD (multiple sulfatase deficiency), one of the more common inborn errors of metabolism. Treatments for these conditions are extremely expensive and leaders from CHOP strive to advocate for patients to have access to these life-changing medications. Our nurse navigators guide families to access every available resource for treatment.
Referring a patient
For doctors seeking a second opinion or who want to refer a patient to the Gene Therapy for Inherited Metabolic Disorders (GTIMD) Program, we offer a dedicated clinical coordinator to help you – and your patients – connect with CHOP. Our GTIMD coordinator helps us collaborate with you, partner with local care teams, and supports patients with scheduling, visits and testing at CHOP. The coordinator provides referring physicians with a direct line of communication, ensuring a smooth transition of care.
For more information about scheduling an appointment for one of your patients, call 267-425-4363 or email GTIMD@chop.edu.
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Our Gene Therapy for Inherited Metabolic Disorders Program team is made up of world-renowned and widely respected experts in metabolic diseases. They are dedicated to finding treatments for every child with an inborn error or metabolism.