The three decades of success of enzyme replacement therapy (ERT) for patients with type 1
Gaucher disease (GD1) have been just a partial success to those patients with the more severe
neuronopathic forms, particularly the children with myoclonic epilepsy or the infants with
type 2 GD.
Ambroxol hydrochloride is an oral mucolytic drug, available over-the-counter (OTC) for many
years as cough medicine. In 2009 it was found (in-vitro) to also act as a pharmacological
chaperone (PC) for mutant glucocerebrosidase (GCase), albeit in a several-fold higher dose .
Unfortunately, due to its low cost, there have been no pharma-driven clinical trials to
establish the use of ambroxol.
In an attempt to provide the proof of concept to the potential use of Ambroxol as PC for
patients with GD, the Gaucher Clinic at Shaare Zedek Medical Center in Jerusalem, Israel, has
treated 12 adult patients with GD1, all untreated with any specific treatment for GD [whether
ERT or substrate reduction therapy (SRT),] with Ambroxol at the OTC dose of 150mg/day for a
period of 6 months; this was not a formal clinical trial, but rather an audit of a series of
patients receiving this drug via the employment of the Israeli Ministry of Health Form 29c to
prescribe it for an off-label indication. A single patient, the thinnest of the group with a
BMI of 17.1, achieved a robust response relative to baseline similar to ERT.
In 2016, a group from Japan has demonstrated impressive neurological response using high-dose
Ambroxol (a marked decrease in seizure frequency, improvement of myoclonus, ability to walk
for a bedridden patient, improvement in the latency of I-V waves and threshold of ABR) with
dramatic change in daily activities and quality of life (QOL). These encouraging results,
that were confirmed in a larger series, yet unpublished, have further led to the conduction
of an investigator-initiated-research (IIR) clinical trial in London by Prof A Schapira,
which has recently been published (January 13, 2020 JAMA Neurology), wherein newly diagnosed
Parkinson patients received high dose Ambroxol, with good safety results