In Review: Rare and Neglected Diseases Symposium 2022

Author: Ryan McArdle

April 25th, 2022: Intellectual Disability

On April 25th, the 2022 Notre Dame Rare and Neglected Diseases Symposium hosted its third session, focusing on Intellectual Disability, with focus Kabuki Syndrome, a rare monogenetic disorder affecting DNA chromosomal structure. The session, moderated by Dr. Jacqueline Harris, featured several presentations by researchers, clinicians, and a panel composed of parents of children with Kabuki Syndrome.


The event began with a presentation by Dr. Harris, who spoke about clinical trials in Kabuki Syndrome. After beginning with a brief summary of the promising prior research on the treatment of Kabuki Syndrome, Dr. Harris went on to speak about an ongoing clinical trial and explained the difficulties in pushing therapeutics for Kabuki Syndrome and for rare diseases more broadly through the clinical trial phases. One of the main focuses of Dr. Harris’s talk was the need for strong biomarkers -- easily accessible metrics which can be used to reliably track the progression of disease and treatment in patients -- and outcome measures -- metrics which can be used to gauge treatment success. Dr. Harris finished her session with an appeal for responsible science and a greater bilateral coordination between researchers in the lab and clinicians working with patients.


Next, Dr. Elizabeth Berry-Kravis gave a presentation on Angelman’s Syndrome, a separate rare monogenetic disorder which causes severe intellectual disability and loss of motor function. Dr. Berry-Kravis began with a summary of the mechanisms of the disease before explaining a promising genetic therapy which can turn on a healthy copy of the gene in patients with Angelman’s Syndrome. Dr. Berry-Kravis then presented several ongoing clinical trials which are using this treatment, with early data on a small number of patients from one of these trials showing substantially improved outcomes for patients on a variety of metrics. Some of the larger themes in Dr. Berry-Kravis’s presentation included the difficulty of creating proper outcome measures for rare diseases, which she argued could be mitigated through stronger communication between families and policymakers, and the brighter future that partnerships with biopharmaceutical companies is providing for patients with rare diseases.


The session then turned to a panel composed of parents of children with Kabuki Syndrome including members of the Kabuki Syndrome Foundation ( who collectively advocated for greater research and funding for the disorder. In addition to sharing several heartwarming anecdotes about their children, the members of the panel gave insights into the collective efforts being made to advocate for Kabuki Syndrome before answering questions about a wide range of topics from the audience. Key insights included the benefits of having the support of a strong network to support their children with Kabuki Syndrome in aspects of educational and social interactions.


Next, Ryan McArdle and Dr. Prasad Padmanabhan, two members of Dr. Kasturi Haldar’s lab at Notre Dame, presented on preclinical laboratory research on neurogenesis in a mouse model of Kabuki Syndrome. After reviewing previous research showing a neurogenesis defect in Kabuki Syndrome mice, Mr. McArdle outlined a promising potential treatment which restored neurogenesis in the Kabuki mouse model. Dr. Padmanabhan then explained the current work being done to try to understand the molecular mechanism of the treatment in the brains of Kabuki Syndrome mice.


Finally, Dr. Christopher Patzke shared a presentation on his work using neurons cultured in the lab as a mechanism for understanding and treating disease. Dr. Patzke began with an overview of neuronal culturing from stem cells before explaining how Cre/Lox, a gene editing technology, could be used to induce disease in otherwise healthy neurons and vice-versa. Dr. Patzke then continued to share how patient blood samples could be used to create more accurate neuronal laboratory models. Dr. Patzke ended by sharing his work studying brain organoids as another promising mechanism for understanding neurologic disorders.


Thanks to all of the presenters, panelists, and audience members for helping to make the Intellectual Disability session at the 2022 Notre Dame Rare and Neglected Diseases Symposium a success!