Inherited metabolic disorders

Metachromatic leukodystrophy (MLD)

Overview

Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the body’s metabolic system (the metabolism are the chemical processes that occur within a living organism to maintain life). It occurs in approximately one in every 100,000 babies (sources: Bonkowski 2010; Poupetova 2010; Lugowska 2011; Kehrer 2011; AL-Jasmi 2012; Stellitano 2016). MLD is caused by a mutation in the ARSA gene or arylsulfatase-A gene. As a result, the body accumulates fatty substances called sulfatides in the brain and other areas of the body, including the liver, the gall bladder, kidneys, and/or spleen. Over time, the nervous system is damaged and patients with MLD will experience neurological problems (such as convulsions, seizures and progressive dementia) and find it more and more difficult to move, talk, swallow, eat and see. There are several forms of MLD which differ by the age at which the symptoms of the disease manifest: late infantile (symptoms before the age of 3 years); juvenile (3 to 16 years) and adult (16 years and above). In the most common and most severe form of MLD (infantile MLD), many children die before their fifth anniversary.

Treating MLD

Currently, there are no effective treatments for MLD. Bone marrow transplantation has not been shown to effectively prevent the progression of the symptoms of MLD to date. It is therefore not considered as a standard of care in this disease. To manage the symptoms of MLD, patients are given medications for seizures and pain, antibiotics and sedatives, on a case-by-case basis. The care of patients may also include physiotherapy and hydrotherapy as well as tube feeding or gastrostomy in the later stages of the disease. The impact of MLD on caregivers and families is considerable.

Our approach

Doctors and scientists have invented a potential new way of treating MLD called “autologous ex vivo gene therapy”. This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own stem cells from the bone marrow or the peripheral blood, using a modified virus that carries the normal gene. This means that the stem cells now have a working copy of the missing gene (that is, the ARSA gene). These genetically modified stem cells are then given back to the patient via an intravenous infusion in a procedure referred to as “hematopoietic stem cell transplant”. After the stem cells are given back to the patient, they can grow and divide into new cells that produce the missing ARSA protein in the brain and in other body tissues.

OTL-200: autologous ex vivo lentiviral gene therapy in clinical development for MLD

Orchard is developing OTL-200, autologous ex vivo lentiviral gene therapy for MLD. For more information, please contact a healthcare professional.

 

Mucopolysaccharidosis type IIIA (MPS-IIIA)

Overview

Mucopolysaccharidosis type IIIA (MPS-IIIA) is a rare and life-threatening inherited disease of the body’s metabolic system (the metabolism are the chemical processes that occur within a living organism to maintain life). It occurs in approximately one in every 100,000 babies. MPS-IIIA is caused by a mutation in the SGSH (or sulfoglycosamine-sulfohydrolase) gene. As a result, the body is unable to breakdown sugar molecules called “mucopolysaccharides”. Over time, these molecules build up in the brain and in other body tissues. Most patients with MPS-III gradually lose their intellectual ability and their ability to walk. Life expectancy is 10-25 years (source: Lavery, Hendriksz, Jones, Orphanet Journal of Rare Diseases 2017).

Treating MPS-IIIA

Currently, there are no effective treatments for MPS-IIIA. Bone marrow transplantation has not been shown to prevent the progression of symptoms of MPS-IIIA and therefore is not considered as a standard of care in this disease.

Our approach

Doctors and scientists have invented a potential new way of treating MPS-IIIA called “autologous ex vivo gene therapy”. This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own blood or bone marrow stem cells, using a modified virus that carries the normal gene. This means that the stem cells now have a working copy of the missing SGSH gene. These genetically modified stem cells are then given back to the patient via an intravenous infusion in a procedure referred to as “hematopoietic stem cell transplant”. After the stem cells are given back to the patient, they can grow and divide into new cells that produce the missing SGSH protein in the brain and in other body tissues.

OTL-201: autologous ex vivo lentiviral gene therapy in preclinical development for MPS-IIIA

Orchard is developing OTL-201, autologous ex vivo lentiviral gene therapy for MPS-IIIA. For more information, please contact a healthcare professional.

 

Mucopolysaccharidosis type IIIB (MPS-IIIB)

Overview

Mucopolysaccharidosis type IIIB (MPS-IIIB) is a rare and life-threatening inherited disease of the body’s metabolic system (the metabolism are the chemical processes that occur within a living organism to maintain life). It occurs in approximately one in every 200,000 babies. MPS-IIIB is caused by a mutation in the NAGLU (N-alpha-acetylglucosaminidase) gene. As a result, the body is unable to breakdown sugar molecules called “mucopolysaccharides”. Over time, these molecules build up in the brain and in other body tissues. MPS-IIIB is very similar to MPS-IIIA.  Most patients with MPS-IIIB gradually lose their intellectual ability and their ability to walk. Life expectancy is 15-30 years (source: Team Sanfilippo Foundation).

Treating MPS-IIIB

Currently, there are no effective treatments for MPS-IIIB. Bone marrow transplantation has not been shown to prevent the progression of symptoms of MPS-IIIB and therefore is not considered as a standard of care in this disease.

Our approach

Doctors and scientists have invented a potential new way of treating MPS-IIIB called "autologous ex vivo gene therapy". This involves making a copy of the normal gene in the laboratory and inserting it into a sample of the patient’s own blood or bone marrow stem cells, using a modified virus that carries the normal gene. This means that the stem cells now have a working copy of the missing NAGLU gene. These genetically modified stem cells are then given back to the patient via an intravenous infusion in a procedure referred to as "hematopoietic stem cell transplant". After the stem cells are given back to the patient, they can grow and divide into new cells that produce the missing NAGLU protein in the brain and in other body tissues.

OTL-202: autologous ex vivo lentiviral gene therapy in preclinical development for MPS-IIIB

Orchard is developing OTL-202, autologous ex vivo lentiviral gene therapy for MPS-IIIB. For more information, please contact a healthcare professional.