We are focused on treating rare, inherited disorders where the disease burden on children, families and caregivers is immense, and where current therapeutic options often do not exist, are suboptimal or are associated with severe complications. Read more about the diseases we’re working on with extraordinary effort and groundbreaking science, and learn why we share families’ sense of urgency to advance the development of investigational therapies.
Neurometabolic disorders are a group of conditions characterized by issues with brain function and metabolism, or the process by which the body converts food into energy.
Metachromatic leukodystrophy (MLD) is a rare and life-threatening inherited disease of the body’s metabolic system. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of fats called sulfatides in the brain and other areas of the body, including the liver, the gallbladder and kidneys. Over time, the nervous system is damaged and children with MLD experience neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures, finding it increasingly difficult to move, talk, swallow, eat and see. Currently, there are no effective treatments for MLD. An estimated 50 percent of children with the most aggressive form of MLD die within five years of disease onset. MLD is estimated to occur in approximately one in every 100,000 live births.
A genetic mutation that results in the build up of fats called sulfatides.
Loss of sensory, motor and cognitive function.
An estimated half of children with the most aggressive form of MLD die within five years of onset.
Sources: Mahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature. Journal of Child Neurology 2010; Kehrer et al. The natural course of gross motor deterioration in metachromatic leukodystrophy. Dev Med Child Neurol. 2011.
Mucopolysaccharidosis type I (MPS-I) is a rare, inherited neurometabolic disease caused by a deficiency of the alpha-L-iduronidase (IDUA) lysosomal enzyme, which is required to break down sugar molecules called glycosaminoglycans (also known as GAGs). The accumulation of GAGs across multiple organ systems results in symptoms including neurocognitive impairment, skeletal deformity, loss of vision and hearing, and cardiovascular and pulmonary complications. MPS-I occurs at an overall estimated frequency of one in every 100,000 live births. There are three subtypes of MPS-I; approximately 60 percent of children born with MPS-I have the most severe subtype, called Hurler syndrome, and rarely live past the age of 10 when untreated.
A genetic mutation that results in the accumulation of complex carbohydrates called glycosaminoglycans
Neurological, skeletal and cardiovascular problems
Children born with the most severe form of MPS-I typically die by the age of 10
Sources: Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759.; Beck et al. The Natural History of MPS I: Global Perspectives from the MPS I Registry. Genetics in Medicine 2014, 16(10), 759.
Mucopolysaccharidosis type IIIA (MPS-IIIA, also known as Sanfilippo syndrome type A) is a rare and life-threatening metabolic disease. People with MPS-IIIA are born with a mutation in the N-sulphoglucosamine sulphohydrolase (SGSH) gene, which, when healthy, helps the body break down sugar molecules called mucopolysaccharides. The buildup of mucopolysaccharides in the brain and other tissues leads to intellectual disability and loss of motor function. MPS-IIIA occurs in approximately one in every 100,000 live births. Life expectancy of children born with MPS-IIIA is estimated to be 10-25 years.
A genetic mutation that results in the buildup of sugar molecules called mucopolysaccharides
Progressive intellectual disability and loss of motor function
Children born with MPS-IIIA rarely live into late-adulthood
Source: Lavery, C., Hendriksz, C.J. & Jones, S.A. Mortality in patients with Sanfilippo syndrome. Orphanet J Rare Dis 12, 168 (2017) doi:10.1186/s13023-017-0717-y
Primary immune deficiencies are a group of rare, genetic disorders in which the immune system does not function properly, leading to frequent infections that can be life-threatening.
Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is a rare, life-threatening, inherited disease of the immune system caused by mutations in the adenosine deaminase (ADA) enzyme that result in a lack of, or minimal, immune system development. The first symptoms of ADA-SCID typically manifest during infancy with recurrent severe bacterial, viral and fungal infections and overall failure to thrive. Without treatment the condition can be fatal within the first two years of life. The incidence of ADA-SCID is currently estimated to be one in 500,000 live births in the U.S. and between one in 200,000 and one in 1 million in Europe.
A genetic mutation that affects white blood cell production
Frequent, severe infections, as well as non-immune symptoms including those affecting the gastrointestinal, skeletal and nervous systems
Children born with ADA-SCID typically die by the age of 2 without treatment
Sources: Orphanet. SCID due to ADA deficiency.; Whitmore KV, Gaspar HB. Front Immunol. 2016;7:314.; Kwan A et al. JAMA. 2014;312:729-738.; Sauer AV, et al. Front Immunol. 2012;3:265.
Wiskott Aldrich syndrome (WAS) is a life-threatening inherited immune disorder that primarily affects males and is characterized by recurrent and severe infections, autoimmunity, eczema and severe bleeding episodes. It is caused by a mutation in the gene that produces the WAS protein, which results in abnormal function of white blood cells and low platelets. Without treatment, the median survival for children born with WAS is 14 years of age. The global incidence of WAS is estimated to be about one in every 100,000 male births per year.
A genetic mutation that affects blood cells
Recurrent, severe infections and severe bleeding episodes
Without treatment, the median survival for children born with WAS is 14 years of age
Source: Malik MA, Masab M. Wiskott-Aldrich Syndrome. [Updated 2019 Jun 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2019 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539838/
IE-002-2200004, July 2022
