Platform technology for direct targeting of therapeutics to neurons


Fusion with a humanized tetanus-toxin C fragment (TTC) targets proteins to neurons


Market Need


Neurological diseases including Alzheimer’s, Parkinson’s and epilepsy, are one of the largest and fastest growing markets with a projected worth of over 1.5 billion dollars in 2012 and large projected growth coinciding with an aging population.  On average, CNS drug development takes at least twice as long as drugs in areas such as cardiovascular in part because of the difficulty that injectable or oral drugs have in penetrating the blood-brain barrier. Thus, there is a need for a technology that can deliver a therapeutics across the blood-brain barrier in order to be effective for these diseases.


Technology Overview


The Wolfe lab has developed a technology by which therapeutic proteins can bypass the blood brain barrier and be delivered to the brain and CNS. The technique involves linking a therapeutic protein of interest to a humanized form of bacterial tetanus-toxin C (TTC) fragment, a protein that enters the central nervous system from the circulation more efficiently than any other known protein. The humanized TTC fragment is transported by neurons via axonal transport without causing clinical symptoms. The Wolfe lab verified this technology by creating an adenovirus encoding beta-glucuronidase (GUSB) fused to the humanized TTC and injecting it directly into the hippocampus of mice, showing that the delivered enzyme was still enzymatically active and had a wider distribution after one month compared to wild-type GUSB. Injections of the vector intramuscularly provided evidence that, through axonal transport, the protein was able to bypass the blood brain barrier to be expressed in the brain. The Wolfe lab also believes that this approach could be useful in treating lysosomal storage diseases, such as Tay-Sachs and Mucopolysaccharidosis, where delivery of a missing enzyme could mitigate disease symptoms. 



•       Targeted delivery of therapeutic protein to neurons

•       Delivery site can be intramuscular as blood brain barrier is bypassed to get to brain and CNS

•       Therapeutic chimera protein delivery is increased in quantity and persists longer compared to wildtype protein delivered via adenovirus


•       Platform technology for delivery of proteins to neurons

•       Delivery of therapeutic proteins to neurons for treatment of neurological disease

•       Treatment of lysosomal storage diseases such as Tay-Sachs and Mucopolysaccharidosis


Stage of Development: In vivo proof of concept



Case ID:
Web Published:
Patent Information:
Title Country Serial No. Patent No. File Date Issued Date
HUMANIZED TTC AND METHODS OF USE THEREOF Canada 2,799,470   5/13/2011  
Humanized TTC and Methods of Use Thereof United States 13/697,885 8,703,733 11/14/2012 4/22/2014
For Information, Contact:
Cassie Tran
Licensing Associate
The Children's Hospital of Philadelphia
John Wolfe
Carlos Gay-Antaki