Adeno-associated virus Glut1 gene therapy for rescuing glucose transport in Glut1 deficiency syndrome

This technology is a therapeutic for glucose transporter type 1 (Glut1) deficiency syndrome that rescues glucose transport to the brain by delivering and integrating functional copies of the Glut1 gene into the genome.

Unmet Need: Treatment to reestablish brain glucose transport in Glut1 deficiency syndrome patients

Glut1 deficiency syndrome is a severe neurological disorder caused by mutations in the glucose transporter type 1 (Glut1) gene, which impair the expression of functional Glut1 protein in the brain and lead to reduced glucose transport across the blood-brain barrier. The lack of sufficient glucose to support the energetic demand of the brain is known to cause seizures, cognitive impairment, and other neurological symptoms. The current treatment for this disease is a ketogenic diet that allows for increased ketone metabolism to supplement the lack of glucose; however, the diet can be difficult to maintain for a lifetime, is not guaranteed to be effective, and can lead to other side effects from nutritional deficiencies. Additional therapies that directly rescue Glut1 function and the transport of glucose to the brain are needed to treat the disease.

The Technology: Gene therapy to rescue Glut1 expression for Glut1 deficiency syndrome treatment

This technology is a therapeutic for Glut1 deficiency syndrome that rescues Glut1 expression in the brain through the transport of functional copies of the Glut1 gene via adeno-associated virus (AAV), which can cross the blood-brain barrier. The functional gene gets inserted into the genome of brain cells, which allows for permanent reestablishment of Glut1 expression. Expression of functional Glut1 in the brain rescues glucose transport into the brain to support energy demands.

This technology has been validated with mouse models.

Applications:

• Gene therapy for Glut1 deficiency syndrome
• Gene therapy for other neurological diseases caused by genetic mutations
• Delivery of gene therapies across the blood-brain barrier

Advantages:

• Single dose of therapy sufficient for a lifetime of treatment
• Rescues physiological glucose transport
• Does not rely on patient compliance with a strict dietary treatment regimen
• Maintains access to all dietary nutrients

Lead Inventor:

Darryl De Vivo, M.D.

Patent Information:

Patent Pending (US20210069292)

Related Publications:

• Tang M, Gao G, Rueda CB, Yu H, Thibodeaux DN, Awano T, Engelstad KM, Sanchez-Quintero MJ, Yang H, Li F, Li H, Su Q, Shetler KE, Jones L, Seo R, McConathy J, Hillman EM, Noebels JL, De Vivo DC, Monani UR. “Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein.” Nat Commun. 2017 Jan; 8: 14152.

Tech Ventures Reference:

• IR CU15054

• Licensing Contact: Kristin Neuman