LILA Holding AG is a Swiss rare disease company developing ambroxol hydrochloride as a pharmacological chaperone therapy for the neurological manifestations of Gaucher disease types 2 and 3.
Neuronopathic Gaucher disease (types 2 and 3) is caused by mutations in the GBA1 gene, leading to deficient glucocerebrosidase (GCase) enzyme activity. This causes toxic accumulation of glucosylceramide in the brain, resulting in progressive neurodegeneration.
Type 2 (acute neuronopathic) is the most severe form, with onset in infancy and a median survival of just 14 months. Type 3 (chronic neuronopathic) causes progressive cognitive decline, seizures, ataxia, and loss of motor function throughout childhood and adulthood.
Current enzyme replacement therapies and substrate reduction therapies effectively manage systemic disease but do not cross the blood-brain barrier, leaving the neurological component entirely untreated.
Ambroxol rescues misfolded GCase enzyme function through a well-characterized molecular mechanism, and is one of very few compounds proven to reach the brain in therapeutic concentrations.
Ambroxol binds mutant GCase at neutral pH in the endoplasmic reticulum, stabilizing the misfolded protein and enabling correct folding and trafficking to the lysosome.
At the acidic pH of the lysosome, ambroxol dissociates from GCase, leaving the enzyme catalytically active. The net result is increased functional GCase where it is needed.
Ambroxol is detected in CSF of all treated patients. In non-human primates, oral ambroxol increased brain GCase activity by 16–24% across brain regions.
Approved as an OTC mucolytic in 50+ countries since 1978. Over 50 million patient-years of post-marketing safety data with no serious adverse events at high doses in published studies.
Off-patent and manufactured worldwide. Affordable even at high therapeutic doses, enabling access in low- and middle-income countries where the majority of nGD patients live.
Migalastat (Galafold), approved by FDA in 2018 for Fabry disease, validates the pharmacological chaperone mechanism for lysosomal storage diseases.
Ambroxol has been studied in neuronopathic Gaucher disease across multiple independent clinical centers worldwide, with over 180 patients treated in published literature.
5 patients (4 GD3, 1 GD2 post-BMT) treated with high-dose ambroxol. Ambroxol was detected in cerebrospinal fluid of all patients, confirming blood-brain barrier penetration. Increased lymphocyte GCase activity was observed in all subjects. Neurological improvements were documented across the cohort.
All patients were L444P/L444P homozygous, on stable ERT background. Ambroxol was administered at 10 mg/kg/day. Neurological improvement or resolution of selected symptoms was observed across treated patients, representing the largest nGD-specific clinical study to date.
One patient treated from 4 months of age showed nearly age-appropriate neurocognitive development in a disease form with a median survival of just 14 months.
The longest published follow-up of high-dose ambroxol combined with ERT. Sustained neurological stability was observed over a full decade of continuous treatment.
Amsterdam UMC-led study confirming ambroxol's tolerability and biomarker effects. CSF penetration and GCase enhancement confirmed across patient cohort.
Compassionate use of high-dose ambroxol in Korean nGD patients, with documented neurological stabilization and favorable safety profile at sustained high doses.
We welcome inquiries from researchers, clinicians, patient advocacy organizations, and regulatory professionals working in the field of Gaucher disease and lysosomal storage disorders.
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Zurich, Switzerland
LILA Holding AG is a Swiss corporation registered in the Canton of Zurich.
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