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.

About Arimoclomol

Arimoclomol is an investigative medicinal product, meaning it is not an approved medicine. We are conducting clinical studies to investigate how effective arimoclomol is as a treatment for a number of diseases. To be approved, all new therapies must be effective and must not cause undue harm. We have studied arimoclomol’s effects thoroughly in the laboratory as well as in clinical trials in healthy human volunteers and are now investigating its effects and safety in patients.


Lysosomal Storage Diseases


Many lysosomal storage diseases are caused by mutations in a protein involved in lipid digestion and transportation. This causes an accumulation of lipid in compartments of the cell called lysosomes, which in turn leads to cell stress and toxicity. When stressed cells are treated with arimoclomol, they are stimulated to produce a natural chaperone called Heat Shock Protein 70 (HSP70), which helps to fold the digestive enzyme into a functional conformation, allowing the cell to process the accumulated lipid.

Neuromuscular Diseases


In rare circumstances, some proteins are vulnerable to aggregation, meaning they clump together and don’t get recycled properly. Aggregations of misfolded proteins cause cell stress, and eventually cell death. When stressed cells are treated with arimoclomol, they are stimulated to produce a natural chaperone called Heat Shock Protein 70 (HSP70), which helps to guide aggregated proteins into the recycling pathway and prevents newly-built proteins from aggregating.

Our Research

The focus of our research is to understand more about the cell-protective properties of heat shock proteins and to create new therapies for degenerative diseases of the central nervous system and muscles.

Heat shock proteins are known as molecular chaperones because they play a role in helping proteins to function properly when cells are under stress. They also help to transport non-functional proteins to the right place inside cells; either to be recovered or broken down.

Lysosomal Storage Disease

Lysosomes are essential compartments of cells, where waste products are sent to be broken down and recycled. They contain enzymes which act like molecular scissors to digest these waste products. If, as a result of a genetic mutation, one of these digestive enzymes doesn’t function properly, then the waste product will accumulate inside the lysosome and eventually become toxic to cells. Digestive enzymes are proteins, and their dysfunction can be the result of a failure to fold into the correct shape or because they are incomplete. In some cases, cells don’t produce a specific digestive enzyme at all. The extent of the digestive enzyme dysfunction depends on the genetic mutations. These mutations are inherited from both parents who are carriers of the mutation.

Broadly, our research in lysosomal storage diseases focuses on the natural cellular machinery that helps proteins to remain folded in their active state. In particular, we conduct research on heat shock protein family members called HSP70, which we have shown to be effective in correcting conditions of lysosomal deficiency by helping to refold non-functional digestive enzymes and guiding them to the lysosome, where they’re needed. Our pre-clinical research focuses on the beneficial effects of increasing the production of HSP70 in Niemann-Pick type C and Gaucher’s disease, as well as several other lysosomal storage diseases. For a more detailed scientific explanation, you can read about the research which underpins our work (Kirkegaard et al. Nature 2010; Kirkegaard et al. Science Translational Medicine 2016).

Neuromuscular Disorders

If a protein doesn’t fold properly or if it is produced in the wrong part of the cell, it can clump together with other proteins, creating accumulations or aggregates. These aggregates can cause the cells stress and toxicity, and are a major component of the pathology in many neurodegenerative and other progressive diseases.

HSP70 has been shown to resolve aggregates and to help chaperone misfolded proteins to be degraded by the cells’ recycling systems. It can also protect newly-built proteins from misfolding and aggregating. Through collaborations with world-leading academic researchers, arimoclomol has been tested in pre-clinical studies to assess the impact of amplifying the production of heat shock proteins in a number of protein aggregation disorders, including sporadic inclusion body myositis (sIBM) and SOD1-associated amyloid lateral sclerosis (SOD1-ALS).



Orphazyme strives to develop its expertise within its therapeutic areas of interest through close collaborations with academic experts and patient organisations. Through these partnerships, Orphazyme supports the advancement of molecular and clinical understandings and performs pre-clinical evaluations in biological models of relevant diseases. 

Orphazyme’s academic partners include academic professors and clinicians from institutions such as the University of Oxford, University Hospital of Udine, University College London, University of Miami, University of Cambridge and University of Kansas.

As an example of such partnership structures, Orphazyme collaborates with Professor Frances Platt at the University of Oxford, a partnership which has lasted almost from the inception of the Company. Professor Platt is an expert in LSD research and pioneered the first pharmacological approach to treat these disorders. Through this collaboration, Orphazyme has conducted a number of pre-clinical studies that have provided insights into the potential of HSP amplifying therapeutic strategies for the LSDs. 

Further, partnerships with the patient community has ensured that patient-relevant outcomes have been assessed in scientific models and subsequently published in peer-reviewed scientific journals.