Fabry disease

Migalastat or Galafold® is a chaperone therapy pill taken every other day to treat Fabry disease. Migalastat is designed to work on the body's natural alpha-galactosidase A enzyme by helping make the misfolded enzyme more stable and chaperoning it to the lysosome to do its job. The enzyme should then be able to break down stored glycolipids and prevent them from being stored in cells within the body. Based on studies that look at the gene changes or disease-causing mutations in people with Fabry disease, about 60% of individuals with Fabry disease have amenable mutations, which means they are responsive to treatment with migalastat and the drug may be an option for them to treat Fabry disease. Individuals with Fabry disease can talk to their doctors to learn if they may be able to take migalastat and check to see if their GLA change is considered amenable at the GLA mutation search website.

A cure for Fabry disease would be a one-time treatment that would prevent all medical issues related to Fabry disease. Currently, we have life-long treatments for Fabry disease, but not a cure.

Treatments are being studied to address the underlying causes of Fabry disease that may someday lead to a cure or at least put the disease "into remission". These treatments include gene therapy, which could add or replace the non-working GLA gene in Fabry patients and help the body make its own alpha-galactosidase A enzyme. Other research includes a gene editing technology called CRISPR that would act as a "spellcheck" and correct the changes or mutation in the non-working GLA gene to a working one. To find additional information about current Fabry disease research or clinical trials, please refer to the Clinical Trials website, talk to the national Fabry support groups, or reach out to your local Fabry treatment center.

The GI symptoms in Fabry are thought to be caused by the storage of globotriaosylceramidee (GL-3) in the body that interferes with nerve and cell function in the GI system. This disrupts how fast the stomach empties, how quickly food moves through the intestine, and other functions of digestion including absorbing nutrients. Treatment with enzyme replacement therapy [Fabrazyme (agalsidase beta) or Replagal (agalsidase alfa)] or chaperone therapy [Galafold (migalastat)] has been shown to help decrease the severity and frequency of GI symptoms.

After an evaluation by a gastroenterologist and the ruling out other non-Fabry related causes of GI issues, doctors may also try symptom-specific medications such as: Reglan (metoclopramide) to help the stomach empty, Zofran (Ondansetron) to reduce nausea and vomiting, pancreatic enzymes to aid digestion, Loperamide (Imodium) to decrease hyperactive contractions in patients with diarrhea, or Amitriptyline to decrease nerve pain and other issues in the GI system. Some individuals with Fabry also find that eating small meals, taking probiotics, and avoiding spicy, lactose-containing, or greasy foods also help decrease GI issues.

Dr. Claire Zar-Kessler at Massachusetts General Hospital is also enrolling in a study to learn more about gastrointestinal issues in Fabry disease.

Doctors who focus on gastrointestinal (GI) issues are called gastroenterologists or GI doctors. Fabry focused healthcare providers and GI doctors work together to learn more about a specific person's GI issues and come up with the best treatment plan. Important things to know when putting together a treatment plan include:

• specific GI symptoms (diarrhea, nausea, vomiting, constipation, pain)
• timing (time of day and how close to times of eating food or drinking)
• frequency (how often they occur)
• severity (how mild or severe they are over time)

Some doctors use charts or questionnaires to record this information, others ask for the information during discussions in person. It is important to note that other common health problems like ulcers, gastroesophageal reflux, poor nutrition, celiac disease, malabsorption, pancreatitis, and vitamin deficiencies can also cause GI symptoms and should be tested for to rule out these disorders which would be unrelated to Fabry disease. These conditions would all be treated differently from Fabry disease.

Patients with Fabry disease may experience psychological symptoms common to other chronic illnesses, including depression and anxiety. Appropriate treatment can help most people who suffer from depression. Current treatments include medications and talk therapies with therapists that ease the impact of depression. The first step in determining a treatment path is a psychological evaluation by a psychiatrist and/or a psychologist. A diagnostic evaluation will include a complete history of symptoms such as: when they started, how long they have lasted, how severe they are, whether the patient had them before and, if so, whether the symptoms were treated and what treatment was given. In individuals affected by Fabry disease, studies have shown that treatment with enzyme replacement therapy (ERT) does improve quality of life, as well as physical health which may help with overall life outlook. Some Fabry centers have psychologists skilled in evaluating or treating Fabry-related depression, anxiety, and panic attacks. Additional information about support groups and strategies for coping with the day-to-day challenges of living with Fabry disease can be found on the Discover Fabry Support online resource.

Patients with Fabry disease may experience psychological symptoms common to other chronic illnesses, including anxiety, panic attacks, and depression. Appropriate treatment can help most people who suffer from anxiety. Current treatments include medications and talk therapies with a psychologist. A number of medications that were initially approved for treating depression have been found to be effective for anxiety disorders as well. If one medication is not effective, others can be tried. In individuals affected by Fabry disease, studies have shown that treatment with enzyme replacement therapy (ERT) does improve emotional as well as physical health. Some Fabry centers have psychologists skilled in treating Fabry related depression, anxiety, and panic attacks. Additional information about support groups and strategies for coping with the day-to-day challenges of living with Fabry disease can be found on the Discover Fabry Support online resource.

Patients with Fabry disease may experience psychological symptoms common to other chronic illnesses, including panic attacks. Effective treatments for panic disorders are available in the form of medications and psychotherapy. These treatments are similar to those used to treat depression and anxiety. In individuals affected by Fabry disease, studies have shown that treatment with ERT does improve emotional as well as physical health. Some Fabry centers have psychologists skilled in evaluating or treating Fabry related depression, anxiety, and panic attacks. Additional information about support groups and strategies for coping with the day-to-day challenges of living with Fabry disease can be found on the Discover Fabry Support online resource.

Please seek help if you think you are depressed, anxious or having panic attacks. Help can be found from your physicians and your family. Remember that depression and anxiety can make some people feel like giving up. It is important to realize that these negative views are part of the disease and may not accurately reflect the actual circumstances. Studies have shown that treatment for Fabry disease does improve quality of life as well as physical health and combining Fabry specific therapy with psychology care can help improve aspects of life. Some Fabry centers have psychologists skilled in evaluating or treating Fabry related depression, anxiety, and panic attacks. Additional information about support groups and strategies for coping with the day-to-day challenges of living with Fabry disease can be found on the Discover Fabry Support online resource.

The timing of initiation for enzyme replacement therapy (ERT) can vary depending on the wishes of the family, the child's symptoms, and the opinions of the doctor. Often, the treating physician will closely monitor gastrointestinal, kidney, and heart functions while also asking questions about the child's energy and pain. They often recommend beginning ERT when symptoms of the disease emerge and begin to affect daily life and when symptoms begin to progress. The parents' wishes are always taken into account when determining the time to begin therapy. At this time, therapy rarely is started before three years of age. Please talk to your Fabry doctor or genetic counselor to come up with the best treatment and monitoring plan.

Enzyme Replacement Therapy (ERT) is a specific medication made to replace the normal enzyme that is missing in a person with genetic conditions. Fabry disease is caused by a deficiency or misfolding of the enzyme alpha-Galactosidase A, or alpha-Gal. Alpha-Gal is one of several enzymes in the body's lysosomes or "recycling centers" responsible for breaking down large substances called glycolipids such as globotriaosylceramide, also called GL-3 or Gb3. Most importantly when alpha-Gal is low, missing, or misfolded, GL-3 builds up in lysosomes throughout the body interfering with normal functioning, causing pain, causing inflammation, and narrowing blood vessels.

In Fabry disease, the replacement enzyme is injected intravenously (IV) every other week and taken up by the cells. Once the medication enters the cells, the enzyme can help breakdown the stored GL-3 and help the cells work better. ERT should stop GL-3 from building up and hopefully slow or stabilize Fabry disease symptoms and health-related problems from getting worse. ERT is not a cure for Fabry disease and needs to be given at least every two weeks as the body metabolizes the replacement enzyme quickly.

In the United States, the only available FDA approved ERT is Fabrazyme (also called agalsidase beta). Outside of the United States, many countries have approved the use of Fabrazyme® and Replagal (agalsidase alfa) for treated Fabry disease.

Chaperone therapy, an oral medication that addresses the lack of Alpha-gal seen in Fabry disease through a different mechanism is also approved for the treatment of Fabry disease inside the United States.

Multiple research studies have looked at the safety and side effects of enzyme replacement therapy and found it to be safe for use in humans. In the studies, the people with Fabry disease given ERT had fewer serious Fabry-related health problems than people with Fabry disease that were not on ERT. While ERT is generally safe and well tolerated, individuals treated with ERT can have infusion-related side effects or reactions. These infusion reactions are usually not life threatening and are most often fixed by slowing the speed of the infusion and giving medications before the infusion starts. The most commonly occurring side effects were fever and shaking (rigors) during the infusions.

Rarely, severe reactions can occur in patients during ERT infusions. Approximately 1% of patients developed anaphylactic or severe allergic reactions. If severe reactions occur, the doctor or nurse will immediately stop the administration of ERT and provide emergency treatment.

For more information about Fabry disease treatment and ERT, please talk to your Fabry doctor or refer to the National Fabry Disease online resource.

Enzyme replacement therapy (ERT) can help stabilize, delay, or prevent the progression of serious health problems if started early in the disease's course. The research studies have shown that ERT reduces the amount of stored glycolipids, specifically globotriaosylceramide or GL-3 in urine, blood, kidney cells, skin cells, and heart cells.

One study with Fabrazyme showed that at 11 months of treatment every other week, 94-96% of patients had no GL-3 in kidney cells on kidney biopsy, 85% of patients' heart cells (myocytes) were clear of GL-3, and all of the patients' skin cells from skin biopsy were clear of GL-3. Over the course of 35 months, patients on ERT were 61% less likely to have a serious Fabry disease event (kidney failure, heart attack, stroke, or death) than untreated patients. Treatment works best in patients treated early in their disease as children or teenagers. Similar data is available for ERT for Agalsidase alfa (Replagal™), another Fabry ERT medication that is not approved for use in the United States by the FDA.

When the amount of GL-3 is reduced in the body, the disease progression should slow. However, depending on the stage of Fabry disease, irreversible damage or scarring may have already been done to some organs. For example, if an individual already has serious kidney disease, ERT cannot stop the kidney failure, but can hopefully increase the time until dialysis/transplant is needed, and reduce the chance of heart disease and strokes. In addition, for an individual who had strokes, the hope is that the ERT will help prevent future strokes, heart attacks, and kidney disease. More research into the effectiveness of ERT and damaged organs is still needed.

It is important that a diagnosis is made before irreversible damage has occurred, as the treatment works best in patients treated early in their disease course.

For more information about Fabry disease treatment and ERT, please talk to a Fabry focused doctor who can be found on the National Fabry Disease online resource.

Enzyme replacement therapy is only part of the treatment for Fabry disease. Patients on ERT will still need yearly monitoring tests to watch for any health problems and will also need to see specialist doctors to treat any problems that arise. Patients will need to continue taking any medications prescribed by their physicians.

For more information about Fabry disease treatment, please talk to a Fabry focused healthcare provider who can be found on the National Fabry Disease online resource.

Experts agree ERT should be started as early as possible. Early intervention with enzyme replacement therapy (ERT) offers the best protection against the complications and health problems related to Fabry disease. In adults, this means beginning ERT as soon as Fabry disease is diagnosed. In children with Fabry disease, the decision to begin therapy is based on the symptoms that they have and discussions of the risks and benefits of ERT with their Fabry disease specialist.

In the United States, many experts recommend treating males and females with classic and non-classic Fabry disease as soon as they have symptoms, such as tingling or pain in their hand or feet or issues with diarrhea and constipation. In people without symptoms, the doctor will look at the family history of Fabry symptoms and the gene change causing Fabry disease and work with them to make a good plan for watching for Fabry disease symptoms and starting treatment. For more information about Fabry disease treatment and ERT, please talk to your Fabry doctor or refer to the National Fabry Disease online resource.

ERT is a life-long treatment. As soon as ERT is stopped, the GL-3 begins storing up again. When this happens, the Fabry symptoms and damage will progress again. ERT is an effective treatment, however it constantly requires infusions every two weeks. Research is currently being conducted to find a longer-lasting treatment. For more information about Fabry disease treatment and the importance of staying consistent with ERT, please talk to your Fabry doctor or refer to the National Fabry Disease online resource.

There are not any detailed studies available that can tell us exactly what happens when you stop enzyme replacement therapy (ERT). We do know that as soon as ERT is stopped, the GL-3 levels begin accumulating again. As per patient reports during a period of ERT medication shortage, we know that patients with Fabry disease often start having Fabry problems, such as diarrhea and extreme tiredness, within a month without ERT. Specific information on how long it takes GL-3 to build up again to previous levels is not available in Fabry disease patients. Studies looking at another lysosomal storage disease, Gaucher disease, found that when ERT is stopped, the storage products built up again quickly in most individuals. Those individuals had a quick regression to the same symptoms they had before beginning ERT. When restarting ERT, it took time to return back to the healthy levels they reached on ERT before stopping. For more information about Fabry disease treatment and the importance of staying consistent with ERT, please talk to your Fabry doctor or genetic counselor.

Small studies of people with Fabry disease after a kidney transplant indicate that enzyme replacement therapy (ERT) is safe and works against the other non-kidney related problems of Fabry disease. In one small study of three kidney transplant patients treated with ERT at a dose of 1 mg/kg every 2 weeks for 13-18 months, the blood plasma GL-3 levels decreased (in all 3 patients), hand/foot/arm/leg pain went away in the one patient experiencing pain, and heart problems were stabilized or improved in 2 out of 3 transplant patients studied. It's important to remember that while the transplanted kidney will have high levels of alpha-galactosidase A to keep the transplanted kidney free of Fabry disease, it typically is not enough enzyme to prevent further Fabry symptoms all over the body. Based on this information, many doctors will recommend staying on ERT to help prevent other Fabry related health problems and events from occurring after kidney transplant. For more information about Fabry disease treatment and ERT after kidney transplant, please talk to your Fabry doctor or genetic counselor.

A Port-A-Cath is a combination of a port and an intravascular device used to get intravenous or IV access in the same spot every time for infusions like enzyme replacement therapy (ERT). The device is located under the skin in the upper part of the chest or other spot connected into a large vein. Surgery, under general anesthesia, is usually needed to place the Port-A-Cath. The Port-A-Cath is not required for infusions, but the benefit of the Port-A-Cath is that it allows for an easy access to a vein for infusions. The downsides include: Port-A-Caths are placed through surgery, which requires general anesthesia, there is a risk of infection with the Port-A-Cath, and although Port-A-Cath can last for years, they may need to be replaced or taken out. Usually Port-a-Caths are put in by general surgeons or interventional radiologists. The decision to get a Port-A-Cath is a personal choice that should be discussed with your physician. If you have questions or would like to learn more about Port-A-Caths, please talk to your Fabry doctor or genetic counselor.

It is important to drink plenty of water the night before and the morning of your infusion. Being well hydrated makes starting the IV for the infusion line much easier, so it's important to be hydrated before all infusions. Note: if you are on dialysis or have another reason for careful fluid intake monitoring, continue to follow your doctor's instructions. On the morning of the infusion, eat breakfast as normal and prepare for a long day. Please talk to your Fabry doctor or genetic counselor for more information about what to expect with ERT treatment and how to prepare for your first infusion.

Depending on the ERT product selected, the first infusion takes approximately 4 hours of actual infusion time and 1 hour after the infusion has ended for monitoring. After several months, the time of infusion can typically be reduced down to 2 hours. You may wish to bring books, a laptop computer, cell phones, etc. A guest/family member/friend may accompany you for your infusion. Depending on where you are having the infusion, you may bring your own lunch, or have a guest pick up lunch for you during the infusion. Please note that if you are infused within a cancer infusion center, they may have restrictions on hot or strong smelling foods. If you receive your infusions at an alternative site, please check with them regarding their food/drink policy.

Before leaving your infusions, make sure to schedule your next infusion. Your infusions should be scheduled every other week.

Please talk to your Fabry doctor or genetic counselor for more information about what to expect with ERT treatment and how to prepare for your first infusion.

If you are receiving enzyme replacement therapy, you may experience infusion-related reactions. If you are feeling sick during an infusion, please let your infusion nurse know right away. They will most likely slow or stop your infusion while the doctor learns more about the symptoms you are experiencing. It may be that simply stopping the infusion briefly and restarting will be enough to stop your symptoms. It may be that taking a medication like Benadryl or a steroid may be needed during this infusion and before the next infusion. Although it is rare, if you are having a more serious immune reaction, they may inject you with an Epi-pen or give you epinephrine. Your healthcare team will let you know if you will be taking new medications before your next infusion, have blood collected for antibody testing, and if the infusion will be slowed down next time.

If you feel any symptoms such as increased leg pain, headache, increased tiredness, chest pain, racing heart, chills, nausea, fever, or itching in the days following your infusion, please notify your physician and/or treatment coordinator immediately.

• Sometimes during an infusion, people can have the following health issues:
• Feeling Cold
• Headache
• Fever
• Breathlessness
• Chest Pain
• Chills
• Nausea
• Itching
• Racing Heart
• Hives or bumps

Some people with Fabry disease feel bloated, tired, have increased leg pain, headache, increased tiredness, chest pain, racing heart, chills, nausea, fever, or itching after their infusion. If you are having these or other health issues after your infusion, please let your health care team and infusion nurse know right away. It may be that taking a medication like Benadryl or a steroid may be needed before the next infusion. Your healthcare team will let you know if you will be taking new medications before your next infusion, have blood collected for antibody testing, and if the infusion will be slowed down next time.

If you reach the 7th infusion with Fabrazyme and haven't had any problems, your doctor and infusion nurse may be able to begin slowly increasing the infusion rate. If you have an infusion related reaction, the time of infusion will be decreased and the speed of the infusion decreased again. After many months of therapy and a gradual increase in the infusion rate, many individuals with Fabry disease can have their infusion over 2 hours.

The manufacturer for Replagal (Shire) does not recommend infusing this product any quicker than 40 minutes.

Please discuss any questions about ERT treatment with your Fabry doctor.

The best source of information on enzyme replacement therapy (ERT) is a doctor specializing in Fabry disease. The National Fabry Disease Foundation has a Fabry specialist finder on their website. Additional information can be obtained from either a Fabry support group or informational websites sponsored by the companies that make ERT. The international organization FIN may also be great resource for those living outside the United States.

It's important to understand that once kidney damage is done to the podocyte (filtering cells of the kidney) and other kidney cell types, it's often difficult, if not impossible to reverse the damage. This is why it's particularly important to work with your Fabry specialist and if they recommend it, visit a kidney doctor (nephrologist) at least once a year. They are the experts most qualified to discuss medications, kidney function, and treatment options with you.

Enzyme replacement therapy (ERT) and chaperone therapy are the only therapies for Fabry disease that address the underlying problem of glycolipid accumulation in the kidney. Many people with Fabry disease will need to combine ERT with another medications, called an angiotensin converting enzyme inhibitors (ACE inhibitor) and angiotensin receptor blockers (ARBs), to reduce the amount of protein in the urine due to kidney filtering problems and to best keep the kidneys working. A nephrologist experienced with Fabry disease can help manage these medications. The National Fabry Disease Foundation has a Fabry specialist finder on their website that can help you find a kidney doctor specializing in Fabry disease and the kidneys.

In addition to enzyme replacement therapy (ERT) or chaperone therapy, individuals with proteinuria and/or high blood pressure may be prescribed blood pressure lowering medicines called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). These medications have been found to protect the kidneys and decrease the amount of protein in the urine. The National Heart, Lung, and Blood Institute recommends that people with diabetes or reduced kidney function should keep their blood pressure below 130/80 mmHg. For more information about maintaining kidney health with Fabry disease, please talk to your Fabry doctor or genetic counselor.

If an individual has Fabry disease and begins enzyme replacement therapy (ERT) with an elevated creatinine level or is already in end-stage renal disease, permanent damage to kidney cells has already occurred. In these cases, ERT or chaperone therapy cannot stop or prevent kidney failure, but can hopefully prolong and/or stabilize kidney function and reduce the chance for complications related to cardiac problems and strokes. Just as in individuals without Fabry disease, if your kidneys stop working correctly, you will need to undergo dialysis or kidney transplantation. If you choose to pursue dialysis, in order to remove the wastes from your body, dialysis must be attended exactly as prescribed by your nephrologist. For more information about maintaining kidney health with Fabry disease, please talk to your Fabry doctor or genetic counselor.

Before becoming pregnant, any woman living with Fabry disease wishing to consider pregnancy should discuss their medications with their doctor and a genetic counselor. Although there are case reports of healthy babies born to mothers on enzyme replacement therapy (ERT), no formal human studies have been done to establish the safety and efficacy of ERT or chaperone therapy for Fabry disease during pregnancy. Accordingly, Fabry specialists and obstetrician/gynecologists (ob/gyn) will work closely together to determine when to stop and start Fabry specific medications during pregnancy.

Other drugs that a woman may be taking to manage symptoms of Fabry, such as Dilantin (Phenytoin) or Tegretol (carbamazepine) for hand and foot pain, may also increase the risk of certain birth defects and developmental delays in an unborn baby. If a woman with Fabry disease becomes pregnant unexpectedly, it is important to consult with a doctor as soon as possible to discuss medication use options.

For more information about Fabry disease and pregnancy, please talk to your Fabry doctor or genetic counselor. A Fabry focused healthcare provider can be found on the National Fabry Disease online resource. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

After an initial diagnosis of Fabry disease, doctors will take a comprehensive medical history to look for signs and symptoms of disease and will also run tests to check kidney function, heart health, and neurological function. Individuals may be referred to a dermatologist for skin examination, to an ophthalmologist for an eye exam, to a cardiologist for check on heart function, to a audiologist for hearing assessment, and to medical genetics and a genetic counselor for a genetics consultation.

The best way to obtain the most accurate, current, clear, and comprehensive information is to be seen at a Fabry focused center that specialize in the treatment of patients with Fabry disease. At most centers you will see a Fabry-focused doctor, genetic counselor, and nurse who work as a team to answer your questions, discuss testing, identify your at-risk family members, and develop a comprehensive evaluation and treatment plan for you. The team will work with your current doctors to organize the treatment, tests, and specialists you need.

In order to find a Fabry disease specialist who can provide more information on Fabry disease, please refer to the National Fabry Disease Foundation online resource. Please also feel free to call the Emory Fabry Center at 800-200-1524 to locate a center in your state.

In the United Kingdom, there are certain centers that specialize in genetic disorders, such as Fabry disease. Speak to your physician about finding a specialist. Other parts of the world also have great resources and centers of excellence for Fabry disease. Again, talking to your doctor can be an important first step in finding a specialist.

Currently there are two medications approved by the Federal Food and Drug Administration (FDA) for treatment of Fabry disease in the United States: an enzyme replacement therapy (ERT) and a chaperone therapy.

The FDA approved enzyme replacement therapy (ERT) treatment for Fabry disease in the United States is called Fabrazyme®, or agalsidase beta, and is made by a company called Sanofi Genzyme Corporation. The goal of ERT is to replace the enzyme missing in individuals with Fabry disease, with artificial or recombinant alpha-Galactosidase A or alpha-Gal, so that their body can breakdown stored glycolipids and prevent them from being stored in cells within the body. Patients getting ERT are infused every other week and receive the enzyme by an intravenous (IV) infusion. When began early in the course of the disease, replacing the enzyme helps slow the progression of the disease, reduces complications, and may even prevent long-term complications. Fabrazyme® is a treatment that can be given to individuals with any mutation or change in the GLA gene.

The FDA approved chaperone therapy for Fabry disease in the United States is called Galafold®, or migalastat, and it made by a company called Amicus Therapeutics. Galafold® is pill taken every other day that is designed to help an individual with Fabry disease's own enzyme work more effectively (chaperone therapy). Galafold® only works for specific mutations in the GLA gene that are considered "amenable". Individuals with Fabry disease can talk to their doctors to learn if they may be able to take Galafold and check to see if their GLA change is considered at the GLA mutation search website.

Along with ERT and chaperone therapy, there are also treatments available to help relieve some of the other symptoms associated with Fabry disease. Drugs such as diphenylhydantoin, carbamazepine and gabapentin have been helpful in reducing nerve pain and tingling in the extremities of individuals with Fabry disease. Individuals with proteinuria and/or high blood pressure may be prescribed blood pressure lowering medicines called angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). These medications have been found to protect the kidneys and decrease the amount of protein in the urine. Lastly, to help relieve some of the gastrointestinal discomfort, medications such as Reglan (metoclopramide) can be used to help the stomach empty, Zofran (ondansetron) to reduce nausea and vomiting, pancreatic enzymes to aid digestion, and Imodium (loperamide) to decrease hyperactive contractions in patients with diarrhea. Some people with Fabry also find that eating small meals, taking probiotics, and avoiding spicy, lactose-containing, or greasy foods also help decrease GI issues.

For more information about Fabry disease treatment please talk to your Fabry doctor or find a Fabry center at the National Fabry Disease online resource.

Fabry is believed to be a good condition to treat with gene therapy because it is caused by a single gene (GLA) and it doesn't take a large amount of working enzyme to make a difference in the medical issues. For gene therapy to work, scientists need to figure out the best way to get the working gene into the right place in the DNA in as many cells as possible WITHOUT causing side effects like an allergic reaction.

Although not yet available to everyone, gene therapy studies in Fabry disease are open to enrolling people with Fabry disease in the United States, Canada, Australia, and other countries. Most of the studies are focused on men with classic Fabry disease at this time, but in future studies women with classic Fabry disease and individuals living with non-classic Fabry disease will be included as well.

Currently, there are several companies (4DMT, Freeline, Sangamo) exploring different methods of doing gene therapy in Fabry disease. While the gene therapy is still in various clinical and preclinical phases of development, it is important to discuss the risk and benefits of participating in clinical trials with new biological agents with a physician familiar with the options.

The easiest way to learn if you are a candidate for a gene therapy trial in Fabry disease is to talk to a healthcare provider that specializes in Fabry disease. However, studies focusing on gene therapy are also posted at clinicaltrials.gov where you can search for "Gene Therapy Fabry disease." It may help to avoid limiting your search to your state or country, as many studies will pay for your travel if you are eligible to join.

Galafold works by helping to stabilize the faulty enzyme in Fabry disease and guiding it into the lysosomes to help break down accumulated lipid waste. Therefore, it is called a chaperone therapy. Once the enzyme has entered the lysosome, the chaperone will detach from the enzyme so it can break down the waste. The every-other-day dosing allows time for the protein to detach and let the enzyme complete its work. This is a case where more is not necessarily better.

The adult dosage of Galafold (migalastat) is 123 mg orally, every other day. The dose should be consumed at the same time of day on an empty stomach. Food should not be consumed 2 hours before and 2 hours after a meal. Capsules should be swallowed whole; do not chew, crush or cut capsules open.

Theoretically, combining chaperone therapy with enzyme replacement therapy (ERT) should stabilize the ERT enzyme and help it enter the lysosome to break down stored material. However, the timing, safety, and effectiveness of treating Fabry disease with both ERT and chaperone therapy has not been established. In addition, access to both could be difficult as insurance will probably not pay for both medications to be used in one individual as it would be considered experimental. Always speak with your Fabry disease specialist before starting or switching to a new treatment.

Individuals with Fabry disease who are 18 years of age or older and have Galafold (migalastat) "amenable mutations" can speak with their doctors to determine if switching from ERT to migalastat may be an option for them. If it is, the Fabry disease specialist will usually collect blood and urine to test biomarkers before therapy is changed and then monitor them again at specific time points after migalastat is begun. The plan for switching a specific patient from ERT to treatment with migalastat is something to ask a Fabry disease specialist. In order to find a Fabry disease specialist who can provide more information on Fabry disease, please refer to the National Fabry Disease Foundation online resource.

Individuals with Fabry disease can talk to their doctors to learn if they may be able to take migalastat (Galafold®) and check to see if their GLA change is considered amenable at the GLA mutation search website. Migalastat is a chaperone therapy pill taken every other day to treat Fabry disease. Migalastat is designed to work on the body's natural alpha-galactosidase A enzyme by helping make the misfolded enzyme more stable and chaperoning it to the lysosome to do its job. The enzyme should then be able to break down stored glycolipids and prevent them from being stored in cells within the body. Based on studies that look at the gene changes or disease-causing mutations in people with Fabry disease, about 60% of individuals with Fabry disease have "amenable mutations" and migalastat may be an option for them to treat their Fabry disease.

The following content is sponsored by Optum Specialty and Infusion Pharmacies.

Home infusions can be a convenient option for many patients living with Fabry disease and receiving enzyme replacement therapy (ERT). When starting ERT, most doctors prefer that patients begin infusions in a hospital or outpatient infusion center. After a period of time - determined by the ordering doctor (usually three to six months) - patients may have the option to transition to home infusions. Patients might be a candidate for home infusion if:

1. They are stable patients who are not having active infusion-associated reactions (often called IARs).
2. They have a safe home environment for the infusions.
3. They have coverage for home infusions and medications through insurance or a patient-assistance program.

If a doctor has decided that a patient is a candidate for home infusions, the next step is working with the drug manufacturer's patient-service programs and case managers or infusion pharmacies such as Optum Specialty and Infusion Pharmacies that provide case management. These specialized teams will investigate home-health nursing options to find one that accepts the patient's insurance, is experienced in ERT, and fits their schedule. Most insurance companies allow home infusion therapy as an alternative to a hospital outpatient infusion center, and these experts will make sure home infusion will work with your insurance plan.

The following content is sponsored by Optum Specialty and Infusion Pharmacies

Studies have shown that home infusion of enzyme replacement therapy (ERT) is a safe and effective alternative for many patients living with Fabry disease. Before beginning home infusions, patients should be stable - meaning they're not having active reactions to infusions. It's also important to make sure home infusion nurses are properly trained on mixing ERT medications, infusing ERT, and managing possible infusion-associated reactions.

The manufacturers of some ERT medications have developed home infusion guides to help with the infusion experience. In addition, some pharmacies experienced with home infusion of ERT, such as Optum specialty and infusion pharmacies, have worked with treatment centers and doctors to further develop training and infusion protocols to simplify the complex treatment of Fabry disease.

The following content is sponsored by Optum Specialty and Infusion Pharmacies.

Most doctors prefer that people who have Fabry disease begin enzyme replacement therapy (ERT) infusions in a hospital or outpatient infusion center. After a period of time - determined by the ordering doctor (usually three to six months or seven to 12 infusions) - many patients have the option to move to home infusions for their therapy.

The waiting period before moving to a home setting for infusions is to make sure the patients are comfortable with infusions and the doctors have time to manage any infusion-associated reactions (IARs) that may occur. Not all people receiving ERT will have IARS, but in clinical trials with Fabrazyme, 59% of patients reported IARs, some of which were severe. Doctors will be looking for signs of IARs so that they can manage them prior to referring patients to home infusions.