Anti-Sense - Recently Approved Gene Therapy

Research TeamUpdates

Using an FDA-approved method, the goal of this research is to reduce polyglucosan bodies in patients with APBD in order to safely slow down the progression of the disease. Polyglucosans are an abnormal form of glycogen that cannot be broken down and used for fuel in the body. Instead they build up to form clumps that can damage cells, especially nerve cells.

This project should result in decreased levels of polyglucosans, representing a new treatment approach for APBD and a possibly cure.

Two major avenues are being explored:

1. Antisense oligonucleotides (ASO).
ASOs are small sequences of DNA that block disease processes by interfering with the production of a particular protein that is their target. In APBD, ASOs would be injected directly into the central nervous system where they can knock down their specific target, glycogen synthase (an enzyme involved in converting glucose to glycogen).

The ASO sequences discovered by ISIS Pharmaceuticals will be injected into APBD mouse models generated by Dr. Akman and Lafora Disease mouse models generated by Dr. Minassian. The goal is to use ASOs in periodic injections for APBD patients to reduce the build up of polyglucosan bodies by glycogen synthase and thus slow down the disease.

2. Triple-helix-forming oligos (TFO).
These are very stable molecules that bind specifically to the DNA sequence they target. TFOs will be used in the same way as ASOs but will have highly specific targeted effects, giving them tremendous potential as gene therapy.

TFOs have already been tested and shown to be able to pass into the nuclei of nerve cells by Dr. Kakhlon. He is now working in collaboration with the Israeli company GeneArrest to use them in periodic injections for APBD patients to reduce polyglucosan bodies by targeting the enzyme glycogen synthase and thus slowing down the disease. APBDRF is also funding the testing of TFOs on glycogen branching enzyme (GBE) in collaboration with Dr. Tropak.

Goal: $300,000.00

$1,167.00 raised

What your donation will fund:

Recent donations have used to purchase glycogensynthase TFO as discussed.

Project donors:

APBDRF- $26,000

The Coddon Family Foundation-$10,000

French MDA Grant- 100,000 euro

Prusiner-Abramsky award for $50,000.

Anonymous Israeli donor $20,000

Anonymous US donor $10,000


We would like to thank Isis  Pharmaceuticals and GeneArrest for funding much of the ongoing research not included in our estimates.