Programs of Excellence

The Programs of Excellence (PoE) at the Orphan Disease Center seek to fill critical gaps in translational research.

Each PoE focuses on a disease or cluster of related diseases with significant unmet need, and in which common therapeutic platforms (i.e., therapeutic antibodies, stem cells, gene therapy, RNAi, genome editing, etc.) can be applied. The goal of each PoE is to achieve substantial treatment effects through the identification and targeting of tractable molecular targets. We prioritize research into restoration of function and/or stabilization of a degenerative process. Each of our PoEs has viable strategies for securing sustainable funding.

The ODC Programs of Excellence support new therapeutic development for a disease while also building a more integrated ecosystem to support drug development while meeting the unique needs of the patient community. Each of our POEs has a committed Director that oversees the progress of the program and highlights needs for the field. Through the POEs we assess the need for research tools (antibodies, cell lines, animal models, etc), translational capabilities, clinical development (i.e.patient registries and natural history, biomarkers, clinical endpoints, etc), and we work closely with patients and patient groups in each of these areas to ensure there is a thorough understanding of the disease and community needs.

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease characterized by progressive muscle weakness and wasting, with eventual paralysis. Patients with ALS lose the ability to walk, speak, swallow, and breathe, which leads to respiratory failure and death.

Read more about our work with Amyotrophic Lateral Sclerosis

CDKL5 Deficiency

CDKL5 deficiency is characterized by epileptic seizures which begin within days or months of birth, and by severe developmental delay affecting neurological functions such as motor control, speech, and cognitive ability. This disorder is caused by mutations in the CDKL5 gene which reduce or eliminate expression or function of the CDKL5 protein, an enzyme that is important for normal brain function.

Read more about our work with CDKL5 Deficiency

Crigler-Najjar Syndrome

Crigler-Najjar syndrome type 1 is an ultra-rare recessive genetic disorder characterized by hyperbilirubinemia and jaundice. Deficiency of the liver enzyme UGT1A1, which is responsible for bilirubin metabolism and excretion, can result in toxic accumulation of bilirubin and the risk of irreversible neurological damage.

Read more about our work with Crigler-Najjar Syndrome


Mucopolysaccharidoses (MPSs) are a family of lysosomal storage diseases, each of which is caused by the absence of a critical enzyme needed for normal lysosomal function. These lysosomal enzymes are needed to degrade mucopolysaccharides, now called glycosaminoglycans (GAGs), as well as other cellular debris.

Read more about our work with Mucopolysaccharidoses

Pilot POE Awardees

The ODC Pilot Programs of Excellence Grant helps Penn and CHOP investigators to engage rare disease communities (patients, clinicians, industry) and build appropriate resources across these communities to improve standards of care or therapeutic development.

Read more about our work with Pilot POE Awardees
Rare Disorders of Immune Dysregulation

Rare Disorders of Immune Dysregulation

The immune system is a multifaceted set of organs, cells, and proteins that work to prevent infection. Abnormalities in the immune system can result in dysregulation, which results in the immune system attacking the body.

Castleman Disease

Castleman Disease

Castleman disease is a rare disease of lymph nodes and related tissue. It is characterized by an abnormal overgrowth of cells of the lymph system that is similar to lymphomas (cancers of lymph nodes). While Castleman disease is not a cancer, in one form of this disease (multicentric Castleman disease) patients eventually develop lymphoma

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann Syndrome

Beckwith-Wiedemann syndrome is a genetic and epigenetic disorder commonly characterized by overgrowth and increased risk for cancer. Aspects include large birth weight and length; enlarged kidneys, liver, pancreas, and/or tongue; one side of the body growing more than the other side; and an increased risk of developing certain cancers during childhood.