A collaboration of researchers from Hadassah Medical Center and the Israeli company Pepticom has resulted in the design of a peptide (a very small molecule) that shows promise for APBD patients. The peptide they designed is identified by its components and has the name “LaTKE." Hadassah researchers have already determined that LaTKE works on cells in a laboratory setting. The next step is to extend testing to an APBD mouse model.
A picture is worth a thousand words
- APBDRF winter 2015 newsletter http://bit.ly/LTKE-N
- Letter from the APBDRF to stakeholders bit.ly/helpLaTKE
Hadassah Medical center
Dr Amit Michaeli answers APBD community questions 12/2O15 See also Dr Kakhlon's comments
1) It looks like the peptide activates the GBE not completely but partially. If so, will that be enough to help reverse the physical and neurological effects of APBD?
It is difficult to say at the moment and we will have a better idea after animal testing. Since APBD is a recessive disease, one copy of the functional enzyme is sufficient to prevent the onset of APBD in heterozygous people. We are hence optimistic about the prospects of partial enzyme recovery.
From Dr. Or Kakhlon
As all researchers reiterate, we are aiming at a cocktail type of therapy for APBD. Except perhaps for amylase introduction into the brain (Drs. Minassian and Melnyk work), no single therapeutic direction is expected to completely cure APBD. If the peptide increases GBE activity from 10% to 30% of healthy control (approximately), this should definitely ameliorate patients condition, as 50% GBE activity is non-symptomatic.
(2) Will activation of the GBE overcome the polyglucosan bodies already accumulated in the neurons? Or do we still need a separate drug to take care of these pre-existing polyglucosan bodies?
This is a critical point indeed. I am a chemist, not a neurologist, so I would direct that question at Prof' Lossos and Dr. Kakhlon. I assume we will have a better idea after animal trials. At any rate, since the disease is normally slow in progression, a drug halting it along with early diagnosis will be significant as well.
From Dr. Or Kakhlon:
We need a separate drug. Correction of GBE activity will only slow down the formation of new polyglucosans. However, if applied early enough, before a critical mass of polyglucosans is formed (for instance before the onset of the disease), enhancing GBE activity could slow down or even prevent disease progression.
(3) How long will it take to test the peptide for FDA approval?
It is too early to estimate. We are currently working on generating a wider pipeline (more derivatives/molecules), this will increase our chances of a successful, timely outcome.
(4) If the peptide has some success, will that obviate the need for taking triheptanoin?
It is far too early to speculate about this. Hopefully, yes, but even a combination of medicines that stop disease progression will be great.
From Dr. Kakhlon:
Please see my reply to question 1. We predict that only an exhaustive therapeutic approach, involving different therapeutics which address different disease mechanisms, will eventually be efficient.
5) Is there a preliminary indication of the peptide's side effects/safety in activating the GBE to more normal levels?
No, there is not. The chances of a natural, 4 amino acid peptide to be toxic are slim. However, the peptide may be metabolized quickly, requiring significant formulation efforts.
LaTKE explanation of acronym
The peptide tested is not CALLED LaTKE. It's amino acid sequence is Leucine-Threonine-Lysine-Glutamate, or in a single letter code, LTKE. It so happens that its pronounciation sounds like the famous Hanukah dish