Grant Awarded to Support Preclinical Studies of Next-Generation Therapy
CRANBURY, NJ, USA I June 25, 2013 I Amicus Therapeutics (FOLD) today disclosed a preclinical Chaperone-Advanced Replacement Therapy (CHART(TM)) program for Mucopolysaccharidosis Type I (MPS I), a lysosomal storage disease caused by missing or deficient alpha-L-iduronidase (IDUA) enzyme. Amicus is developing a proprietary human recombinant IDUA (rhIDUA) enzyme co-formulated with a novel pharmacological chaperone as a next-generation therapy for MPS I.
The pharmacological chaperone is designed to improve tissue uptake and reduce the immunogenicity of rhIDUA by stabilizing the enzyme in its properly folded and active form. In addition, in support of its development of a proprietary rhIDUA enzyme, Amicus has received a grant of up to approximately $250,000 from a private U.S.-based donor that provides medical research grants to find better treatments and cures for rare genetic disorders, including lysosomal storage diseases.
David J. Lockhart, Ph.D., Chief Scientific Officer of Amicus Therapeutics, said, “This grant expands our preclinical work and supports our development of a next-generation therapy for MPS I. Our goal is to engineer a proprietary, potentially bio-better rhIDUA enzyme that may be further improved by the addition of a pharmacological chaperone stabilizer. First-generation ERT for MPS I has helped to improve certain manifestations of the disease, however, rhIDUA is highly immunogenic. Directly co-formulating rhIDUA with a chaperone has the potential to increase enzyme stability in the infusion bag and in circulation, enhance uptake of active enzyme in disease-relevant tissues, and potentially reduce immunogenicity.”
In people with MPS I, missing or deficient IDUA leads to the accumulation of complex carbohydrates that can affect physical abilities, organ and system functioning, as well as mental and skeletal development. First-generation ERT (laronidase) with rhIDUA has been shown to improve walking capacity and pulmonary function in people with MPS I. However, most patients who receive laronidase develop anti-rhIDUA antibodies, and the laronidase label carries a black-box warning that cites life-threatening anaphylactic reactions in some patients during infusion.1 Amicus believes it may be able to improve upon the properties of the rhIDUA enzyme itself, while also incorporating a pharmacological chaperone stabilizer.
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, stated, “Our MPS I program is an additional step forward for our CHART platform technology to combine proprietary enzymes with novel pharmacological chaperones across the lysosomal storage diseases. Importantly, the grant funding supports our internal biologics capabilities at Amicus, which we are leveraging alongside our expertise with chaperones to develop next-generation therapies for people living with lysosomal storage diseases.”
About Amicus Therapeutics
Amicus Therapeutics (FOLD) is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing novel, first-in-class treatments for a broad range of human genetic diseases, with a focus on delivering new benefits to individuals with lysosomal storage diseases. Amicus’ lead programs include the small molecule pharmacological chaperones migalastat HCl as a monotherapy and in combination with enzyme replacement therapy (ERT) for Fabry disease; and AT2220 (duvoglustat HCl) in combination with ERT for Pompe disease.
About Chaperone-Advanced Replacement Therapy (CHART(TM))
The Chaperone-Advanced Replacement Therapy (CHART(TM)) platform combines unique pharmacological chaperones with enzyme replacement therapies (ERTs) for lysosomal storage diseases (LSDs). In a chaperone-advanced replacement therapy, a unique pharmacological chaperone is designed to bind to and stabilize a specific therapeutic enzyme in its properly folded and active form. This proposed CHART mechanism may allow for enhanced tissue uptake of active enzyme, greater lysosomal activity, more reduction of substrate, and lower immunogenicity compared to ERT alone. Improvements in enzyme stability may also enable more convenient delivery of next-generation therapies. Amicus is leveraging the CHART platform to develop pharmacological chaperones co-administered with currently marketed ERTs as well as proprietary next-generation therapies that consist of lysosomal enzymes co-formulated with pharmacological chaperones.
About Mucopolysaccharidosis Type I (MPS I)
Mucopolysaccharidosis Type I (MPS I) is a severe, fatal, multi-system lysosomal storage disease which can affect physical abilities, organ and system functioning, as well as mental and skeletal development. It is caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase, which leads to the accumulation of complex carbohydrates known as glycosaminoglycans (GAGs).
The incidence of MPS I is estimated to be at about 1 in 100,000 births. MPS I is typically classified into three categories: 1) Hurler Syndrome, the most severe form involving progressive developmental delay, physical problems, and death within the first decade of life, 2) Hurler-Scheie Syndrome, an intermediate form characterized by physical symptoms and normal or near-normal cognitive ability, and 3) Scheie Syndrome, an attenuated form in which individuals may have normal cognitive ability, average height, skeletal deformities and an average life span.
SOURCE: Amicus Therapeutics
Post Views: 652
Grant Awarded to Support Preclinical Studies of Next-Generation Therapy
CRANBURY, NJ, USA I June 25, 2013 I Amicus Therapeutics (FOLD) today disclosed a preclinical Chaperone-Advanced Replacement Therapy (CHART(TM)) program for Mucopolysaccharidosis Type I (MPS I), a lysosomal storage disease caused by missing or deficient alpha-L-iduronidase (IDUA) enzyme. Amicus is developing a proprietary human recombinant IDUA (rhIDUA) enzyme co-formulated with a novel pharmacological chaperone as a next-generation therapy for MPS I.
The pharmacological chaperone is designed to improve tissue uptake and reduce the immunogenicity of rhIDUA by stabilizing the enzyme in its properly folded and active form. In addition, in support of its development of a proprietary rhIDUA enzyme, Amicus has received a grant of up to approximately $250,000 from a private U.S.-based donor that provides medical research grants to find better treatments and cures for rare genetic disorders, including lysosomal storage diseases.
David J. Lockhart, Ph.D., Chief Scientific Officer of Amicus Therapeutics, said, “This grant expands our preclinical work and supports our development of a next-generation therapy for MPS I. Our goal is to engineer a proprietary, potentially bio-better rhIDUA enzyme that may be further improved by the addition of a pharmacological chaperone stabilizer. First-generation ERT for MPS I has helped to improve certain manifestations of the disease, however, rhIDUA is highly immunogenic. Directly co-formulating rhIDUA with a chaperone has the potential to increase enzyme stability in the infusion bag and in circulation, enhance uptake of active enzyme in disease-relevant tissues, and potentially reduce immunogenicity.”
In people with MPS I, missing or deficient IDUA leads to the accumulation of complex carbohydrates that can affect physical abilities, organ and system functioning, as well as mental and skeletal development. First-generation ERT (laronidase) with rhIDUA has been shown to improve walking capacity and pulmonary function in people with MPS I. However, most patients who receive laronidase develop anti-rhIDUA antibodies, and the laronidase label carries a black-box warning that cites life-threatening anaphylactic reactions in some patients during infusion.1 Amicus believes it may be able to improve upon the properties of the rhIDUA enzyme itself, while also incorporating a pharmacological chaperone stabilizer.
John F. Crowley, Chairman and Chief Executive Officer of Amicus Therapeutics, stated, “Our MPS I program is an additional step forward for our CHART platform technology to combine proprietary enzymes with novel pharmacological chaperones across the lysosomal storage diseases. Importantly, the grant funding supports our internal biologics capabilities at Amicus, which we are leveraging alongside our expertise with chaperones to develop next-generation therapies for people living with lysosomal storage diseases.”
About Amicus Therapeutics
Amicus Therapeutics (FOLD) is a biopharmaceutical company at the forefront of therapies for rare and orphan diseases. The Company is developing novel, first-in-class treatments for a broad range of human genetic diseases, with a focus on delivering new benefits to individuals with lysosomal storage diseases. Amicus’ lead programs include the small molecule pharmacological chaperones migalastat HCl as a monotherapy and in combination with enzyme replacement therapy (ERT) for Fabry disease; and AT2220 (duvoglustat HCl) in combination with ERT for Pompe disease.
About Chaperone-Advanced Replacement Therapy (CHART(TM))
The Chaperone-Advanced Replacement Therapy (CHART(TM)) platform combines unique pharmacological chaperones with enzyme replacement therapies (ERTs) for lysosomal storage diseases (LSDs). In a chaperone-advanced replacement therapy, a unique pharmacological chaperone is designed to bind to and stabilize a specific therapeutic enzyme in its properly folded and active form. This proposed CHART mechanism may allow for enhanced tissue uptake of active enzyme, greater lysosomal activity, more reduction of substrate, and lower immunogenicity compared to ERT alone. Improvements in enzyme stability may also enable more convenient delivery of next-generation therapies. Amicus is leveraging the CHART platform to develop pharmacological chaperones co-administered with currently marketed ERTs as well as proprietary next-generation therapies that consist of lysosomal enzymes co-formulated with pharmacological chaperones.
About Mucopolysaccharidosis Type I (MPS I)
Mucopolysaccharidosis Type I (MPS I) is a severe, fatal, multi-system lysosomal storage disease which can affect physical abilities, organ and system functioning, as well as mental and skeletal development. It is caused by a deficiency of the lysosomal enzyme alpha-L-iduronidase, which leads to the accumulation of complex carbohydrates known as glycosaminoglycans (GAGs).
The incidence of MPS I is estimated to be at about 1 in 100,000 births. MPS I is typically classified into three categories: 1) Hurler Syndrome, the most severe form involving progressive developmental delay, physical problems, and death within the first decade of life, 2) Hurler-Scheie Syndrome, an intermediate form characterized by physical symptoms and normal or near-normal cognitive ability, and 3) Scheie Syndrome, an attenuated form in which individuals may have normal cognitive ability, average height, skeletal deformities and an average life span.
SOURCE: Amicus Therapeutics
Post Views: 652
