Advances in the Treatment of METABOLIC DISORDERS

The foods we eat every day are filled with the building blocks of life: carbohydrates, amino acids, and fats. But to use these materials, the body must break down complex foods into these simpler, usable forms. Any problems in this process, which is called metabolism, can cause a metabolic disorder, many of which are rare and difficult to treat.

Fabry Disease
Gaucher Disease
Mucopolysaccharidosis VI

Fabry Disease

Patients with Fabry disease are deficient in a particular enzyme involved in the breakdown of fats, which causes a buildup of fat in their blood vessels and organs. The symptoms of this potentially fatal genetic disorder are diverse and can make diagnosis difficult.⁶ They include burning sensations in the hands and feet, skin rash, excessive sweating, fever, severe gastrointestinal problems after eating, and cloudiness of the eye. Fabry disease patients often survive into adulthood but are at increased risk of strokes, heart attack and heart disease, digestive problems, and kidney failure. Fabry disease affects an estimated 1 in 117,000 people, most of whom are male.^7,8

Patient Perspective: Fabry Disease - Many Symptoms, One Disease

PHARMACEUTICAL ADVANCES
The First to Attack Fabry Disease at Its Root
Agalsidase beta, approved in 2003, is the first drug that treats the cause of Fabry disease rather than lessening its symptoms. This enzyme replacement reduces the accumulated fat within the blood vessels and organs and decreases the symptoms of the disease.⁹

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Gaucher Disease

Gaucher disease, another rare metabolic disorder, is a deficiency of the enzyme glucocerebrosidase, which breaks down and recycles glucosylceramide. The deficiency causes quantities of this fatty substance to accumulate in the spleen, liver, lungs, bone marrow, and, in rare cases, the brain.¹⁰ This buildup results in bruising, clotting difficulties, fatigue, enlargement of the liver and spleen, weakening of the skeleton, and in some instances, lung and kidney impairment.

This rare genetic disorder is classified into three different types based on clinical severity and course, and by the presence or absence of neurological complications. An estimated 6,000 individuals in the United States have Gaucher disease.^11,12

PHARMACEUTICAL ADVANCES
Oral Treatment for Patients who Need Another Option
For patients who cannot receive the standard enzyme treatment due to allergies, hypersensitivity, or poor venous access, miglustat, an oral treatment, was approved in 2003 for treatment of mild to moderate disease.¹³ Miglustat works by reducing the production of glucosylceramide so that the available glucocerebrosidase enzymes are not overwhelmed and are able to properly break down the substance and clear it from the body.¹⁴ Miglustat is proven to decrease the size of the liver and spleen and increase platelet and hemoglobin levels, which decreases bruising and fatigue.¹⁵

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Mucopolysaccharidosis VI

Patients with mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, face many health problems, which can be devastating depending on the severity of the disease.

In MPS VI, patients lack a particular enzyme called arylsulfatase B, which breaks down and recycles glycosaminoglycan (GAG), a complex sugar. GAGs are used to provide structure for various tissues including bones, cartilage, skin, and airways. When GAGs accumulate, however, they can cause a variety of symptoms including thickening of the nose, lips, and tongue; breathing problems due to narrowed airways; short stature; frequent ear infections leading to hearing loss; heart disease as a result of malfunctioning heart valves, thickening of the heart muscle, and narrowed blood vessels; and stiff joints.¹⁶ Because the signs and symptoms are so varied, diagnosis is often difficult and delayed. The disease is also quite rare; approximately 1,100 people worldwide have MPS VI.¹⁷

PHARMACEUTICAL ADVANCES
First Therapy Targeted Toward Cause of Devastating Genetic Disorder
Approved in 2005, galsulfase is the first enzyme replacement therapy for MPS VI to treat the cause of the disorder by breaking down the built-up stores of GAGs instead of improving symptoms related to the disease.^18,19 Because of the problems associated with the disease, patients with MPS VI often become tired easily and cannot withstand long periods of physical activity. In clinical trials, galsulfase was shown to improve the walking and stair-climbing capacity of patients.²⁰

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Endnotes:

6 Fabry Community, Health Care Professionals, http://www.fabrycommunity.com/healthcare/fc_p_hc_overview.asp (accessed 13 September 2005).
7 National Institute of Neurological Disorders and Stroke, "NINDS Fabry's Disease Information Page," National Institute of Neurological Disorders and Stroke, http://www.ninds.nih.gov/disorders/fabrys/fabrys.htm (accessed 12 May 2005).
8 Fabry Community, Fabry Disease Overview, http://www.fabrycommunity.com/patient/about/fc_p_pt_fabry-disease.asp (accessed 12 May 2005).
9 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-media, Inc., Fabrazyme®, http://cp.gsm.com (accessed 10 May 2005).
10 National Institute of Neurological Disorders and Stroke, "NINDS Gaucher's Disease Information Page," National Institute of Neurological Disorders and Stroke, http://www.ninds.nih.gov/disorders/gauchers/gauchers.htm (accessed 12 May 2005).
11 National Tay-Sachs and Allied Diseases Association, Inc., Gaucher Disease, http://www.ntsad.org/pages/gaucher.htm (accessed 12 May 2005).
12 National Organization for Rare Disorders, Gaucher Disease, http://www.rarediseases.org/search/rdbdetail_fullreport_pf (accessed 30 August 2005).
13 National Gaucher Foundation, Prevention and Treatment of Gaucher Disease, http://www.gaucherdisease.org (accessed 12 May 2005).
14 S. Reents et al., Clinical Pharmacology, Gold Standard Multi-media., Inc., Zavesca®, http://cp.gsm.com (accessed 10 May 2005).
15 Actelion Pharmaceuticals US Inc., "Balance at Work in Patients Naive to ERT," Zavesca®, http://www.zavesca.com/HP_PNE.html (accessed 12 May 2005).
16 The National MPS Society, A Guide to Understanding Maroteaux-Lamy Syndrome, http://www.mpssociety.org/images/pdfs/booklets/MPS%20VI%20final.pdf
(accessed 29 September 2005).
17 MPSVI.COM, http://www.maroteauxlamy.com/pc/faq/faqs.asp (accessed 29 September 2005).
18 CenterWatch, Naglazyme, http://www.centerwatch.com/cgi-bin/cl.pl?p=patient/drugs/dru885.html (accessed 29 September 2005).
19 BioMarin Pharmaceutical Inc., Naglazyme Dosing and Administration Guide, http://www.naglazyme.com/includes/DoseAdminBroch.pdf (accessed 29 September 2005).
20 BioMarin Pharmaceutical Inc., "Clinical Support Materials," Naglazyme, http://www.naglazyme.com/csm.asp (accessed 29 September 2005).
21 Food and Drug Administration, "Office of Orphan Products Development," Budget 2006, http://www.fda.gov/oc/oms/ofm/budget/2006/PDFs/Summary/Pages194thru199.pdf (accessed 7 September 2005).