Rare Diseases Treated with Enzyme Replacement Therapy

Rebekah Harrison

Enzyme replacement therapy (ERT) is commonly used to treat patients with lysosomal diseases.
Here are 7 rare diseases that are treated with ERT:

Gaucher Disease

Gaucher disease is an inherited genetic disorder that affects many of the body's organs and tissues. There are a few forms of Gaucher. Type 1, also called non-neuronopathic Gaucher disease because the brain and spinal cord are usually not affected. Types 2 and 3 Gaucher disease are known as neuronopathic forms of the disorder because they are characterized by problems that affect the central nervous system. Type 2 Gaucher disease usually causes life-threatening medical problems beginning in infancy. Type 3 Gaucher disease also affects the nervous system but it tends to worsen more slowly than type 2.
Signs and symptoms include hepatomegaly and splenomegaly, joint pain, neurological issues and osteoporosis.
Three ERTs currently approved to treat Gaucher disease Type 1 are:
Cerezyme (imiglucerase for injection):  the gold standard for ERT and has been treating people with Gaucher disease since 1994. It is administered by intravenous infusion every 2 weeks.
Vprive (velaglucerase alfa for injection): Vpriv was approved in March 2010 of Vpriv and has also been shown to relieve or reverse many of the signs and symptoms of Type 1 Gaucher disease.  It is also an enzyme replacement therapy and administered by intravenous infusion every 2 weeks.

Elelyso (taliglucerase alfa): Elelyso was approved by the FDA in June 2012 for the treatment of Gaucher disease type 1.  It has not been given approval in Europe (based on the argument that Elelyso and Vpriv are too similar).  The key biochemical difference of Elelyso compared to the above enzyme replacement therapies is that it is derived from plant (carrot). It is administered by intravenous infusion every 2 weeks.

Hunter Syndrome

Hunter syndrome [mucopolysaccharidosis type II (MPS II)] almost exclusively affects young males. Boys with MPS II are deficient in the enzyme iduronate-2-sulfatase that helps breakdown glycosaminoglycans (GAG). The net result is that GAG builds up in cells and organs throughout the body. That build up can lead to a plethora of symptoms although in the more severe cases, the physical features of the condition (stunted growth, course facial features, stiff joints, intellectual disability) are fairly uniform and can begin around age 2-4 years of age. The severe form often includes progressive cognitive impairment and a life span of approximately 12-15 years old. In more mild forms, the condition may go undiagnosed for many years as it does not feature intellectual impairment or regression.
Signs and symptoms include stunted growth, coarse facial features, impaired intelligence, hearing loss, joint stiffness and thickening of heart valves.
Elaprase (idursulfase) is the only orphan treatment currently approved for Hunter syndrome in the United States. Another ERTcalled Hunterase (idursulfase-beta) is approved in South Korea. The current formulation for Elaprase does not cross the blood brain barrier so it cannot help children with intellectual impairments.

Fabry Disease

Fabry disease is an X-linked lysosomal storage disorder that leads to excessive deposition of globotriaosylceramide ( GL-3) throughout the body. Skin, eye, kidney, heart, brain, and peripheral nervous system are highly vulnerable.
The condition is caused by deficiency of the enzyme alpha-galactosidase A (alpha-Gal A) which degrades GL-3. The accumulation of GL-3 is believed to cause a variety of symptoms, including pain, kidney failure, and increased risk of heart attack and stroke.
Currently, the only treatment available is Fabrazyme (agalsidase alfa) which is infused over several hours every 2 weeks.

Pompe Disease

Pompe disease is a rare lysosomal disease that may present in childhood (early-onset) or in adulthood (late-onset). In both cases, the disease is due to a deficiency in the enzyme alpha-glucosidase (GAA).  
Symptoms include diminished muscle weakness, hypertrophic cardiomyopathy, liver enlargement, respiratory difficulties and hearing loss.
Genzyme’s Lumizyme (alglucosidase alfa) is for patients with infantile-onset Pompe disease, including patients less than 8 years of age as well as for patients with late-onset Pompe disease.

Maroteaux-Lamy Syndrome

Maroteaux-Lamy syndrome, also known as MPS VI is caused by a deficiency in arylsulfatase B (ARSB).
Signs and symptoms include neurological complications such as clouded corneas, deafness, pain from compressed nerves and thickening of dura matter.
Naglazyme (glasulfate) is approved for the treatment of Maroteaux-Lamy syndrome to improve growth and joint movement. The drug costs $365,000 a year which makes it one of the world’s most expensive drugs.

Morquio A syndrome

Morquio A syndrome (also called MPS IV) is a lysosomal disorder in which patients produce an insufficient amount of active N-acetylgalactosamine-6-sulfatase enzyme (GALNS) or have inactive GALNS. As a result, damaging levels of keratan sulfate and chondroitin-6-sulfate accumulate in the tissues and organs, causing pervasive skeletal and joint abnormalities, cardiopulmonary disease, and other clinical manifestations.
Sings and symptoms include abnormal heart development, large fingers, dwarfism, widely spaced teeth and compression of spinal cord.
BioMarin’s Vimizim (elosulfate alfa) is an ERT which replaces the missing GALNS.

LAL Deficiency

Lysosomal acid lipase (LAL) deficiency is a rare autosomal recessive lysosomal storage disease where the body does not produce enough active lysosomal acid lipase (LAL or LIPA) enzyme. The lack of the LAL enzyme can lead to a build-up of fatty material in a number of body organs including the liver, spleen, gut, in the wall of blood vessels and other organs. Symptoms include feeding difficulties, vomiting, diarrhea, weight loss and abdominal distension.
Alexion’s Kanuma (sebelipase alfa) is the most recent ERT to be approved by the FDA.
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