What We’re Working On

May 2017

Antisense approach:

·ASOs mediated degradation of targeted mRNA by RNaseH.

· ASO mediated correction of mRNA splicing

· Decreases glycogen synthase -by targeting GS and PTG.

· Corrects intronic mutation in compound heterozygote patients, Same mechanism as FDA approved -Spinraza for SMA 4/2017-

Animal model proof of concept research completed for   APBD and Lafora -Ionis building

Humanized GS mouse model Dr Akman building mouse model and proof of concept research

Be prepared with patient population should Ionis decide to move forward

Received Penn Med grant

Ionis Pharma/
Dr. Minassian is preparing manuscript


Ionis Pharma

Dr. Akman

TGM5 Stabilize existing p.Y329S GBE protein Will be included in clinical trials in Hadassah. Paper submitted to J Lipid Res is being revised for resubmission Seeking regulatory guidance for US trial Drs. Escriba, Kakhlon, Caraco, Lossos

Lipopharma BEGA

Guaiacol Decrease glycogen synthase activity publication expected in a few months/

Will be included in clinical trials in Hadassah

Seeking regulatory guidance Drs. AkmanYue,
Lossos, Caraco/


On cures within reach platform

Ibudilast/ Guaifenesin Decreases glycogen or glycogen synthase activity Dr. Akman proof of concept animal model research Seeking regulatory guidance Dr. Akman/ Received Penn Med grant
Triheptanoin Alternative energy source or stabilizer of GBE with p.Y329S.




Clinical trial ended 12/15

Safety confirmed

Study unblinded 2016, efficacy is inconclusive Dr. Schiffman



PMI Small Molecule Screening Project


High content Screening multi-parametric analysis of skin fibroblasts from APBD and Lafora patients- This work is part of the generation of the APBD biobank – we believe that this inclusive biobank is crucial for personalizing APBD       therapy


Mouse studies in progress. Paper is submitted to Biochem J is being revised for resubmission


Received Israel Ministry of Science grant


Prof Weil, / Dr. Kakhlon


Peptide (LTKE)-Pharmacophore project Stabilizes existing GBE with p.Y329S by FDA approved molecular mimics of the LTKE peptide in patient derived PBMC cells. Looking for significant improvement of GBE activity. There are 22 more molecules to test Pharmacophore candidates being tested IsrAPBDf and the APBDRF supporting Dr. Kakhlon’s salary Dr. Kakhlon

Dr. Yue


Prof. Goldblum

LTKE Peptide project Stabilization of GBE p.Y329S Effect in cells published in 2015. Awaiting funding for tests in mice Looking for funding to test in mice. Proof of concept in cells already published in 2015 Dr Kakhlon

Dr Yue


Prof. Goldblum

Other research assets Columbia APBD Registry CAP, NORD/APBDRF Natural History Study Registry (FAN), APBD Biobank skin fibroblasts Columbia University PI Dr. DiMauro/ NORD/ Dr. Kakhlon

February 2016

Potential DRUG


Anti-Sense approach: ASOs and RNase-H Decrease glycogen synthase -by targeting GS, PTG, and glycogenin  Effect is on p.Y329S exonic mutation. Animal model POC (Lafora/APBD) in progress. Expect results mid 2016. If successful, Ionis   needs to build

humanized GS mouse model

Ionis Pharma. Dr. Minassian
Anti-sense approach: Alternative splicing Reverse the intronic mutation responsible for compound heterozygote patients. Development of mouse model and POC proposed, reviewed by SAB, & recommended on (12/2015). Ionis, Dr. Akman
TGMO (2) Stabilize existing GBE 2nd Proposal received 12/2015-Waiting for manuscript Drs. Escriba, Kakhlon, Akman
Guaiacol Decrease glycogen synthase activity POST POC Proposal with SAB and grants being submitted Dr Akman, Dr Kakhlon
Terpin Decrease glycogen synthase activity Awaiting proposal. Dr Akman
Triheptanoin Alternative energy source Clinical trial ended 12/2015 – to be unblinded soon Dr Schiffmann/ Ultragenx -not funded by APBDRF
Peptide Stabilize existing GBE SAB review underway. Partners being sought Dr Kakhlon

Dr Yue


TFOs Decrease glycogen synthase activity Awaiting proposal Dr Kakhlon
PMI Project High Content Screening (HCS) A 3 year proposal received. SAB review underway. Partners being sought. Tel Aviv University, Dr Kakhlon
POC = Proof of Concept