Our Approach

At Orphazyme our work is focused on the cell-protective properties of the heat shock response, a natural defence mechanism in all our cells. The heat shock response protects cells from an accumulation of misfolded proteins or other waste products, which would otherwise lead to toxicity and disease. The heat shock response is generated through the production of heat shock proteins, which act as the cells’ lifeguards.

Today, Orphazyme’s technology is based around a drug called arimoclomol, which stimulates an increased production of heat shock proteins in cells experiencing stress or toxicity.

When we began our company, our focus was on making a positive difference for patients with rare diseases with a high unmet need. In line with this, today we are working to create new therapeutic approaches for a number of different rare diseases, including Niemann-Pick type C, Gaucher’s disease, sporadic Inclusion Body Myositis (sIBM) and  Amyotrophic Lateral Sclerosis (ALS). Our aim is to slow or even prevent disease progression and we believe our approach has the potential to dramatically improve the lives of those suffering from a range of degenerative diseases which currently don’t have satisfactory treatments.

About heat shock proteins

The HSPs constitute a natural system that makes other proteins work correctly and guard against the toxicity arising from misfolded proteins and dysfunctional cellular recycling systems.

In particular, HSPs are molecular chaperones that promote the survival of stressed cells by re-folding misfolded proteins into their correct conformation, or by directing ‘terminally’ misfolded protein to be broken down. They also protect cells by inhibiting lysosomal membrane permeabilisation; stabilising lysosomes (cellular structures where waste products are broken down), allowing cells to clear away waste and return to their normal status.

There are several different types of HSPs which work in conjunction – a cardinal member is HSP70, which Orphazyme uses as the key parameter to measure activity of its drug candidates (“HSP70”). HSP70 has been shown to protect against the formation of protein aggregates which are the defining characteristic of a number of neurodegenerative diseases including ALS and sIBM.
In addition, HSP70 has been identified as a co-factor for lysosomal sphingolipid breakdown, a necessary step in the metabolism of stored lipids which cause toxicity if accumulated in the lysosome.

In both NPC and Gaucher disease, as well as other LSDs, mutations lead to misfolding and loss of enzyme functions involved in the breakdown and recycling of critical cellular components within the cells recycling centres, the lysosomes. By amplifying the production of HSPs, this pathological cascade can be addressed by rescuing the function of the recycling enzymes and helping them perform better in the lysosomes.