Roberto Giugliani, MD, PhD, discusses the RAINBOW clinical trial testing the tolerability and safety of nizubaglustat for Niemann-Pick type C and GM2 gangliosidosis.
Niemann-Pick Type C
Niemann-Pick disease is a genetic metabolic disorder in which abnormal amounts of lipids build up in the brain, spleen, liver, lungs, and bone marrow. Defective or insufficient amounts of enzymes are unable to break down lipids into smaller components to provide energy for the body. Type C may appear early in life or develop in the teen or adult years. It is caused by a lack of the NPC1 or NPC2 proteins. Symptoms may include:
- Ataxia
- Loss of muscle tone
- Brain degeneration
- Increased sensitivity to touch
- Spasticity
- Slurred speech
- Swallowing and feeding difficulties
There is currently no curative therapy for Niemann-Pick disease, with treatment focusing on symptom management.
GM2 Gangliosidosis
Hexosaminidase A deficiency results in a group of neurodegenerative disorders caused by intralysosomal storage of the specific glycosphingolipid, GM2 ganglioside. The prototype hexosaminidase A deficiency is Tay-Sachs disease, also known as the acute infantile variant. Tay-Sachs disease is characterized by:
- Progressive weakness
- Loss of motor skills
- Decreased attentiveness
- Increased startle response beginning between ages three and six months with progressive evidence of neurodegeneration including: seizures, blindness, spasticity, eventual total incapacitation, and death, usually before age four years.
The juvenile (subacute), chronic, and adult-onset variants of hexosaminidase A deficiency have later onsets, slower progression, and more variable neurologic findings, including:
- Progressive dystonia
- Spinocerebellar degeneration
- Motor neuron disease
- A bipolar form of psychosis
RAINBOW Phase 2 Clinical Trial
The RAINBOW study is a randomized, double-blind, placebo-controlled, multicenter trial occurring over the course of 12 weeks. The goal is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of two doses of nizubaglustat in patients with GM2 gangliosidosis or Niemann-Pick type C. Nizubaglustat is a small molecule, oral treatment that is brain penetrant with a unique dual mode of action.
The trial is ongoing with results expected mid-2024.
For more information on Niemann-Pick disease, GM2 gangliosidosis, and other rare lysosomal storage disorders, visit https://checkrare.com/diseases/lysosomal-storage-disorders/
