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 SOD1-associated Amyotrophic Lateral Sclerosis (SOD1-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 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 Disease


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.

Protein Aggregation Disorders


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).

Protein aggregation 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).


Our Collaborations

Orphazyme brings together the latest research excellence, and we are proud to have strong ties with some of the world’s leading academic and clinical partners. Together we are uncovering new knowledge and driving towards understanding protein misfolding diseases and lysosomal instability.

We are proud members of the BatCure consortium for Batten Disease research.


Arimoclomol Programme

    Lysosomal Storage Disease

  • Niemann-Pick Type C

    • Niemann-Pick type C (NPC) is a lysosomal storage disease affecting around 1 in 150,000 newborns and is caused by mutations in the NPC1 or NPC2 genes which are inherited from both parents
    • It is marked by an accumulation of lipid molecules in structures called lysosomes in the cells of internal organs and the central nervous system
    • NPC results in a range of motor and cerebral impairments including progressive loss of muscle control and intellectual capacity
    • NPC diagnosis is usually in childhood, and the prognosis is generally poor: the majority of NPC patients die before the age of 20 and very few live into middle age
    • Currently there is only one approved therapy for NPC, and that has only been approved for use in the EU. It is called miglustat, and it extends life by a few months in a sub-group of patients
    • Based on preclinical experiments indicating that arimoclomol may correct the underlying pathology of NPC we are currently conducting a phase II/III study in children and adolescents suffering with NPC to investigate the effects of arimoclomol on disease progression

    Click here for more information about the trial

  • Gaucher's Disease

    • Gaucher’s disease is a lysosomal storage disease which affects around 1 in 100,00 newborns
    • It is a recessive, autosomal genetic disorder, meaning both parents must be carriers of the mutation to pass on the condition, and is caused by mutations in the GBA gene
    • There are three subtypes, but all are marked by an accumulation of lipid molecules in lysosomes of the cells in a number of different organs around the body, including the spleen, liver and central nervous system (types 2 & 3 only). White blood cells called macrophages are particularly vulnerable to lipid accumulation in Gaucher’s disease
    • There are approved treatments for Gaucher’s disease, including enzyme replacement therapy and substrate reduction therapy, along with symptom management, however these therapies do not address the central nervous system manifestations of the disease
    • Based on encouraging preclinical experiments with arimoclomol we are advancing our pre-clinical Gaucher’s disease programme and aim to advance our clinical programme in the near future

  • Protein Aggregation Disorders

  • SOD1-ALS

    • Amyotrophic lateral sclerosis (sometimes called motor neurone disease or Lou Gehrig’s disease) is a rapidly progressing neurodegenerative disorder
    • Although rare, ALS is the most common neuromuscular disease, affecting around 3-4 in 100,000 individuals from all backgrounds
    • The cause of ALS is not clearly understood, with genetic errors in at least 13 genes implicated in some (but not all) ALS cases – mutations in the SOD1 gene were the first discovered genetic link to ALS, but SOD1 mutations are only found in 1-2% of ALS patients. In fact, up to over 90% of ALS cases are sporadic, meaning there is no family connection to the disease
    • People with ALS are usually diagnosed at age 40-60 and the prognosis is poor, with most patients dying within 3 years of diagnosis. Only ~20% of patients survive for 5 years after diagnosis
    • There is no cure for ALS, and no new treatments have been approved in the EU/US since Riluzole that has a moderate effect on survival was approved in 1995
    • Encouraging results have come from preclinical experiments and in particular from an investigator-led phase II trial into the effects of arimoclomol in SOD1-associated ALS. We are now meeting with regulatory authorities to agree on the next steps for the development of arimoclomol for SOD1-ALS

  • sIBM

    • Sporadic inclusion body myositis is marked by a progressive atrophy of the muscles, particularly in the legs, arms and neck
    • Approximately 40 in 100,000 people are diagnosed with sIBM, but it is slightly more common in men than women
    • sIBM generally presents in adulthood. Increasing muscle weakness leads to progressive disability and in the more severe cases to death is caused by respiratory or the inability to swallow
    • The pathology involves inclusion bodies inside cells, which are caused by aggregations of a range of different proteins which clump together and cause the cells stress and toxicity
    • Preclinical experiments and a phase II study into the effects of arimoclomol in sIBM has produced encouraging results and we are moving forward with clinical research in this disease

New Molecular Entities