Novel Gene Therapy for Treating Cystathionine Beta-Synthase Enzyme Deficiency in Homocystinuria

FCCC Ref. 474-WK


Cystathionine beta-synthase (CBS), a central enzyme in the trans-sulfuration pathway, plays an essential role in homocysteine (Hcy) metabolism in eukaryotes. In healthy normal individuals, CBS-mediated conversion of Hcy to cystathionine is the rate-limiting intermediate step of the essential amino acid methionine (Met) metabolism to cystein. In patients with genetic mutations in the CBS enzyme, the conversion of Hcy to cystathionine is slowed or absent, resulting in elevated levels of the enzymatic substrate in the serum and urine of those individuals. This clinical condition is collectively known as homocystinuria. Clinical manifestations of CBS deficiency include cardiovascular disease with a predisposition to thrombosis, resulting in a high rate of mortality; tissue problems affecting the ocular system with progressive myopia and lens dislocation; tissue problems affecting the skeleton characterized by marfanoid habitus, osteoporosis, and scoliosis; and central nervous system problems, including mental retardation and seizures. The current treatment of CBS deficiency involves lowering patients' total Hcy levels by a combination of dietary Met restriction and vitamin supplementation, but has poor clinical outcomes. Thus, novel approaches are needed for treatment of homocystinuria and its life-threatening complications.

Summary of the Invention

Scientists at Fox Chase Cancer Center and Weill Cornell Medical College developed a gene therapy vector that successfully corrected the disease in a mouse model of CBS deficiency. The successful pre-clinical data justify human trials of gene therapy in CBS-deficient patients.


• Novel gene therapy vector for treating homocystinuria caused by CBS-deficiency.
• Efficient and safe in vivo delivery of wild-type human CBS gene.
• Pre-clinical data exist.

IP Status

Provisional patent application was filed.