Pipeline

GM1 Gangliosidosis is a hereditary, progressive disease mostly impacting neurons in the brain and spinal cord, caused by mutations in GLB1, the gene that encodes the beta-galactosidase (GLB) enzyme. These mutations result in the misfolding and subsequent dysfunction of GLB, which leads to the toxic substrate accumulation of GM1 ganglioside in organs and tissues. Very limited and investigational symptomatic treatment options include substrate reduction therapy, enzyme replacement therapy, bone marrow transplantation, stem cell transplantation and gene therapy to address non-CNS symptoms. Gain is developing allosteric regulators that are designed to decrease toxic substrate accumulation in organs and tissues of patients with GM1 Gangliosidosis in order to potentially provide the first treatment approach for the disease’s neurological symptoms.

Gaucher disease is the most common lysosomal storage disease and is caused by mutations in GBA, the gene that encodes the beta-glucocerebrosidase (GCase) enzyme. These mutations result in the misfolding and subsequent dysfunction of GCase, which leads to the toxic buildup of fat in a variety of organs and tissues such as the liver, spleen, bones and central nervous system (CNS). While there is currently no cure for these patients, enzyme replacement therapy can be used to address non-CNS symptoms. Gain is developing allosteric regulators that are designed to increase GCase activity and decrease toxic fat accumulation in the CNS of patients with Gaucher disease in order to potentially provide the first treatment approach for the disease’s neuronopathic symptoms. 

Parkinson’s disease is a neurodegenerative disorder that affects more than 6 million people worldwide. In most cases, the exact cause of Parkinson’s disease is unknown; however, mutations in GBA1, the gene that encodes the beta-glucocerebrosidase (GCase) enzyme, have been tied to the disease. These mutations result in the misfolding and subsequent dysfunction of GCase, which leads to the toxic accumulation of synuclein and neuronal cell death. There is no cure for Parkinson’s disease and available treatments can only manage individual symptoms. Gain is developing allosteric regulators that are designed to increase GCase activity and decrease neuronal cell death to potentially become the first to develop a treatment for this devastating disease.

Mucopolysaccharidosis type 1 (MPS 1) is a rare lysosomal storage disease that is caused by mutations in IDUA, the gene that encodes the alpha-L-iduronidase (IDUA) enzyme. These mutations cause the misfolding and dysfunction of IDUA, which leads to the toxic buildup of large sugars in the bone, cartilage, cornea, heart and central nervous system (CNS). There is currently no cure for these patients; however, enzyme replacement therapy and hematopoietic stem cell transplant are used to manage the non-CNS symptoms. Gain is developing allosteric regulators to increase IDUA activity and decrease toxic sugar accumulation in the CNS of patients with MPS 1 to potentially become the first treatment for the disease’s neuronopathic symptoms.

Krabbe disease is a severe neurodegenerative disorder caused by mutations in GALC, the gene that encodes the galactosylceramidase (GALC) enzyme. These mutations cause GALC misfolding and dysfunction, which leads to the toxic buildup up fats in the central nervous system (CNS) and ultimately leads to the demyelination and death of neurons. There is no cure for this disease and most patients will die before the age of two. Gain is developing allosteric regulators to restore GALC function and potentially limit neuronal cell death, potentially providing the first treatment option to patients who are in desperate need.