A Novel Gene Medicine Approach for the Treatment of Rare Early Onset Diseases

LogicBio Therapeutics, Cambridge, MA


The field of gene therapy has experienced a renaissance in recent years, having rebounded from the clinical setbacks of decades past.  The field now sits on the cusp of the first approval of a gene therapy product in the US with Spark Therapeutic’s Luxturna for inherited retinal disease. This, coming on the heels of the approval of Glybera in Europe, is likely to pave the way for more good news with products in development for hemophilia A and B, spinal muscular atrophy, lysosomal storage diseases (including Hurler, Hunter, and Sanfilippo syndrome) and countless other monogenic rare diseases. While these new therapies bring much needed hope to patients with grave diseases there are many that will continue to suffer, their diseases unaddressable by the current state of the art technologies. These patients include children with liver related genetic diseases. Unlike neurons and retinal cells, the hepatocytes in the liver multiply extensively during childhood development and regenerate often in adulthood. This makes it difficult to provide young patients with a durable gene therapy. Companies like LogicBio Therapeutics is working on novel gene medicine approach for rare childhood diseases. 

LogicBio Therapeutics, Inc. (LogicBio) is a gene therapy company, based in Cambridge, MA, with a mission to develop lifelong cures for serious, early-onset rare diseases with great unmet medical need. The company is differentiated from other gene therapy approaches by a platform technology (GeneRideTM) developed in the laboratory of Professor Mark A. Kay at Stanford University. This technology, first published in 2015 (Barzel et al. Nature 2015), expands on the classical gene therapy approach by leveraging a natural cellular process to stabily deliver the critical missing gene without external promoters or nucleases. This process, called homologous recombination, enables specific incorporation of therapeutic genetic material using the body’s natural process.    The result is a unique platform that may have the potential to cure pediatric metabolic diseases including organic acidemias. In many rare genetic diseases, such as inborn errors of metabolism, symptoms arise in the first year of life and progress rapidly so early intervention is critical.. By hitching its therapeutic transgene to a natural promoter and using its GeneRide technology early on in a child’s life, it should enable permanent expression of a functional version of the missing or faulty gene.

​GeneRide based treatments have demonstrated efficacy in several animal disease models, including methylmalonic acidemia (Chandler et al. Mol Ther 2017), hemophilia B (Barzel et al. Nature 2015), Crigler-Najjar syndrome (Porro et al. EMBO Mol Med 2017), alpha‑1‑antitrypsin deficiency (Borel et al. Mol Ther 2017), and an infectious disease (unpublished). In even the most severe disease models, GeneRide improved survival and clinically relevant symptoms when given to neonatal mice. Based on these promising animal results, LogicBio intends to conduct additional animal research to ensure the safety of the therapy and to identify the appropriate dose for patients. When these studies are complete, LogicBio will submit the data to regulators in support of clinical trials in patients.

Kelly Blackburn


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