Intervista a Ferdiando Squitieri sullo studio Novartis con la molecola "Branaplam", prossimo a partire

Huntington disease: Ferdinando Squitieri's interview on the Novartis's trial with "Branaplam"


We enthusiastically welcome Novartis' interest in Huntington's disease. Evidence shows that the molecule Branaplam may have a potential effect on the huntingtin protein, while its efficacy is being evaluated in Spinal Muscular Atrophy (SMA).

Novartis currently provides very partial information in its press releases, so it is not yet possible to have details on the biological mechanisms of the drug and the clinical strategies.

We asked Ferdinando Squitieri to help us understand something more about it. 


"Branaplam" reduces the messenger RNA that favors the formation of the huntingtin protein from the HTT gene: What does it mean

Branaplam acts on a biological process called splicing, which is the way in which the starting DNA is cleaned of its less useful parts (introns) in order to allow the translation of the genetic language of the useful parts of DNA (exons) into proteins with functional effects.

this drug reduces only the mutated protein or even the healthy one?

Branaplam reduces the levels of messenger RNA that generate the huntingtin protein by interfering with this biological mechanism of splicing in an apparently non-selective way (both the levels of the normal and the mutated protein are reduced) and in a percentage not yet disclosed by the Company.

why do other trials use "invasive" techniques instead of a capsule taken orally?

Because the strategy of huntingtin protein's reduction is not identical for all molecules, neither is the bioavailability of the drug which, in this case, appears to be able to cross the blood-brain barrier to reach the nervous system. The lumbar puncture may not be necessary in this case except to monitor the protein levels in the nervous system, if the Company will find it necessary.

Why will the study start directly from phase 2 / b?

Because the Company is confident that the data already collected for Spinal Muscular Atrophy (SMA) makes unnecessary to start from preliminary study phases (phase 1, phase 2).

Which patients can take part to the study? 

The early manifest ones, as it is for all the trails that aim to act on the course of the disease.

Do we already know the sites involved in the trial and its duration?

We currently do not have these information.

What is your opinion about the study?

There are too few elements to give an opinion, but I consider this approach extremely encouraging. It surely represents one of the most anticipated experimental innovations in the near future.