How Do Heat Shock Protein Stimulators Work?

Heat shock protein stimulators are a novel class of medications used in the treatment of Niemann-Pick disease type C (NPD-C/NPC) in adult and children 2 years and older. Heat shock protein stimulators reduce the neurological symptoms associated with NPC, and slow down the progression of disease.

Niemann-Pick disease is a rare progressive genetic disorder that affects fat metabolism inside cells. NPD is a lipid storage disorder, caused by the body’s inability to break down lipids inside cells. This leads to accumulation of lipids in various tissues including the liver, spleen, lungs and brain, and damage to these organs.

NPD had been earlier classified into subtypes A, B, and C. Presently, researchers have discovered that NPD-C is a distinct disorder caused by mutations in NPC1 (type C1) or NPC2 (type C2) gene. Types A and B are caused by changes in SMPD1 gene, which cause a deficiency in an enzyme required for fat breakdown, and are now known by the name acid sphingomyelinase deficiency.

All cells have membrane-bound organelles known as lysosomes that break down proteins, carbohydrates and fats. The NPC1 and NPC2 genes encode for proteins that transport lipids from the lysosomes. The mutated NPC genes do not produce sufficient functional proteins, which hampers the movement of lipids, allows them to accumulate in the lysosomes, and cause cellular and organ damage.

Niemann-Pick disease C causes enlargement of liver and spleen, lung disease, and neuromuscular and psychiatric disorders. NPC causes progressive loss of tissue in the brain, and reduced production of myelin. Myelin is a protective layer made of fats and protein that forms a sheath around nerve cells and helps transmission of nerve signals.

Heat shock proteins (HSPs) are a family of proteins that the body produces naturally in response to stressful conditions, such as heat, cold, injury or disease. HSPs play an important role in repairing damaged cells by enabling proper folding of proteins and degradation of misfolded proteins.

Heat shock protein stimulators work by activating heat shock proteins in the cells affected by disease. This helps normal folding of proteins, and processing of accumulated lipid in lysosomes. It improves myelination and protects brain cells from further damage. Arimoclomol, (Miplyffa) is the first drug in this class of drugs to be approved by the FDA recently, to be used in combination with miglustat.

Heat shock protein stimulators are administered as oral capsules. On September 20, 2024, the FDA approved arimoclomol, the first heat shock protein stimulator, to be used in combination with another drug, miglustat, for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and children 2 years and older.

Side effects of heat shock protein stimulators include the following:

• Upper respiratory infection
• Diarrhea
• Decrease in weight
• Decreased appetite
• Lower respiratory tract infection
• Tremor
• Seizures
• Headache
• Hypersensitivity reactions including:
• Hives (urticaria)
• Swelling of tissue under the skin and mucus membranes (angioedema)
• Increase in creatinine
• Low platelet level in blood (thrombocytopenia)
• Embryofetal toxicity

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of heat shock protein stimulators include:

• arimoclomol
• Miplyffa