Scientists at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have received $21.8 million in grants from the California Institute for Regenerative Medicine, the state’s stem cell agency, to develop and advance new stem cell-based treatments for neuropsychiatric disorders, a blood disorder and a neurodevelopmental condition.
Uncovering therapeutic targets for neuropsychiatric disorders
Dr. Aparna Bhaduri, assistant professor of biological chemistry
Bhaduri’s $10.3 million foundational research award will support her work to uncover metabolic drivers of neuropsychiatric disorders. One in five people in the U.S. experience a neuropsychiatric disorder, with many cases starting in adolescence. Current treatments focus on managing symptoms, but there’s an urgent need to develop more effective therapies to address the root biological causes of these disorders. This project aims to fill this gap by investigating the role of metabolism in human brain development and neuropsychiatric disorders at key developmental stages.
Bhaduri and collaborators will use stem cell-derived 3D brain organoid models grown from samples from patients with schizophrenia and autism spectrum disorder to compare how metabolism drives development in a healthy versus disrupted environment. The team, comprised of UCLA, UCSF and UCSC experts in metabolism, computational biology and neurodevelopmental disorders, has also created an innovative technological framework that models neurovascular interactions and has the flexibility to mix and match neural and vascular cells from control or affected individuals — a system that will help pinpoint which cell types are affected by these conditions and how. This work immediately paves the way for innovative, targeted therapies that include dietary interventions and new drugs to transform care.
Gene therapy for alpha thalassemia major
Dr. Donald Kohn, distinguished professor of microbiology, immunology and molecular genetics
Kohn’s $5.6 million translational research award will help advance a stem cell gene therapy for alpha thalassemia, an inherited blood disorder that reduces the body’s production of hemoglobin. Without enough hemoglobin to carry oxygen in the blood, patients with this condition are prone to health issues such as anemia and bone deformities. Those with the most severe type, alpha thalassemia major, face serious challenges, including a dependence on lifelong blood transfusions, severe organ damage and early death due to iron overload. While a bone marrow transplant from a matched donor could be curative, the procedure carries the risk of graft versus host disease, a condition in which transplanted cells attack their recipient’s body.
The therapy Kohn and his team are developing involves collecting a patient’s own blood stem cells, adding the missing alpha-globin gene, then transplanting the modified cells back into the patient. This one-time treatment eliminates the risk of rejection of donor cells and offers a safer, potentially curative option for patients with alpha thalassemia major.
Gene therapy for Angelman syndrome
Dr. Roger Hollis, project scientist in the laboratory of Dr. Donald Kohn
Hollis has been awarded a $5.8 million translational research award to support his development of a gene therapy to treat Angelman syndrome, a rare genetic disorder that affects the nervous system. Individuals with the syndrome require lifelong care as the disease causes a universal lack of speech, impaired motor function and balance, and profound difficulties with sleep. There’s no cure or effective therapeutic options for the disorder.
Hollis is developing a gene therapy approach in which scientists modify a patient’s own blood stem cells using a viral vector to add a healthy copy of the mutated gene that causes Angelman syndrome and then return them back into the patient. Since the disease is caused by a mutation in a single gene, UBE3A, the treatment is intended to be curative or to greatly diminish the debilitating symptoms. The data to date, funded by TransformaTx Biotherapeutics, a biotechnology company founded by the Foundation for Angelman Syndrome Therapeutics (FAST), has demonstrated complete symptomatic correction in the commonly used adult mouse model of the disease. The team will be using the new CIRM grant to prepare a pre-IND package submission to the U.S. Food and Drug Administration, which is the first step toward launching a phase 1 clinical trial to evaluate the therapy in humans.
