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Liver transplantation has proven to be effective for ATTR familial amyloidosis due to Val30Met mutation.
Alternatively, a European Medicines Agency approved drug Tafamidis or Vyndaqel now exists which stabilizes transthyretin tetramers comprising wild type and different mutant subunits against amyloidogenesis halting the progression of peripheral neuropathy and autonomic nervous system dysfunction.
Currently there are two ongoing clinical trials undergoing recruitment in the United States and worldwide to evaluate investigational medicines that could possibly treat TTR.
The drug tafamidis has completed a phase II/III 18-month-long placebo controlled clinical trial
and these results in combination with an 18-month follow-on study demonstrated that Tafamidis or Vyndaqel slowed progression of FAP, particularly when administered to patients early in the course of FAP. This drug is now approved by the European Medicines Agency.
The US Food and Drug Administration's Peripheral and Central Nervous System Drugs Advisory Committee rejected the drug in June 2012, in a 13-4 vote. The committee stated that there was not enough evidence supporting efficacy of the drug, and requested additional clinical trials.
In the absence of a liver transplant, FAP is invariably fatal, usually within a decade. The disadvantage of liver transplantation is that approximately 10% of the subjects die from the procedure or complications resulting from the procedure, which is a form of gene therapy wherein the liver expressing wild type and mutant TTR is replaced by a liver only expressing wild type TTR. Moreover, transplanted patients must take immune suppressants (drugs) for the remainder of their life, which can lead to additional complications. In late 2011, the European Medicines Agency approved the transthyretin kinetic stabilizer Tafamidis or Vyndaqel discovered by Jeffery W. Kelly and developed by FoldRx pharmaceuticals (acquired by Pfizer in 2010) for the treatment of FAP based on clinical trial data. Tafamidis (20 mg once daily) slowed the progression of FAP over a 36-month period and importantly reversed the weight loss and muscle wasting associated with disease progression.
TCAs include imipramine, amitriptyline, desipramine, and nortriptyline. They are generally regarded as first or second-line treatment for DPN. Of the TCAs, imipramine has been the best studied. These medications are effective at decreasing painful symptoms but suffer from multiple side effects that are dose-dependent. One notable side effect is cardiac toxicity, which can lead to fatal abnormal heart rhythms. Additional common side effects include dry mouth, difficulty sleeping, and sedation. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.
Typical opioid medications, such as oxycodone, appear to be no more effective than placebo. In contrast, low-quality evidence supports a moderate benefit from the use of atypical opioids (e.g., tramadol and tapentadol), which also have SNRI properties. Opioid medications are recommended as second or third-line treatment for DPN.
A range of medications that act on the central nervous system has been found to be useful in managing neuropathic pain. Commonly used treatments include tricyclic antidepressants (such as nortriptyline or amitriptyline), the serotonin-norepinephrine reuptake inhibitor (SNRI) medication duloxetine, and antiepileptic therapies such as gabapentin, pregabalin, or sodium valproate. Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.
Symptomatic relief for the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. The evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option. Local anesthesia often is used to counteract the initial discomfort of the capsaicin. Some current research in animal models has shown that depleting neurotrophin-3 may oppose the demyelination present in some peripheral neuropathies by increasing myelin formation.
High-quality evidence supports the use of cannabis for neuropathic pain.
The treatment of peripheral neuropathy varies based on the cause of the condition, and treating the underlying condition can aid in the management of neuropathy. When peripheral neuropathy results from diabetes mellitus or prediabetes, blood sugar management is key to treatment. In prediabetes in particular, strict blood sugar control can significantly alter the course of neuropathy. In peripheral neuropathy that stems from immune-mediated diseases, the underlying condition is treated with intravenous immunoglobulin or steroids. When peripheral neuropathy results from vitamin deficiencies or other disorders, those are treated as well.
The most effective treatment is autologous bone marrow transplants with stem cell rescues. However many patients are too weak to tolerate this approach.
Other treatments can involve application of chemotherapy similar to that used in multiple myeloma. A combination of melphalan and dexamethasone has been found effective in those who are ineligible for stem cell transplantation, and a combination of bortezomib and dexamethasone is now in widespread clinical use.
There is no standard course of treatment to slow or stop the progression of the disease. sIBM patients do not reliably respond to the anti-inflammatory, immunosuppressant, or immunomodulatory medications. Management is symptomatic. Prevention of falls is an important consideration. Specialized exercise therapy may supplement treatment to enhance quality of life. Physical therapy is recommended to teach the patient a home exercise program, to teach how to compensate during mobility-gait training with an assistive device, transfers and bed mobility.
Physical therapy is the predominant treatment of symptoms. Orthopedic shoes and foot surgery can be used to manage foot problems.
Treatment depends on the type of amyloidosis that is present. Treatment with high dose melphalan, a chemotherapy agent, followed by stem cell transplantation has showed promise in early studies and is recommended for stage I and II AL amyloidosis. However, only 20–25% of people are eligible for stem cell transplant. Chemotherapy and steroids, with melphalan plus dexamethasone, is mainstay treatment in AL people not eligible for transplant.
In AA, symptoms may improve if the underlying condition is treated; eprodisate has been shown to slow renal impairment by inhibiting polymerization of amyloid fibrils.
In ATTR, liver transplant is a curative therapy because mutated transthyretin which forms amyloids is produced in the liver.
People affected by amyloidosis are supported by multiple organizations, including the Amyloidosis Foundation, Amyloidosis Support Groups Inc., and Amyloidosis Australia, Inc.
No drug has been shown to be able to arrest or slow down the process of this condition. There is promise that two drugs, tafamidis and diflunisal, may improve the outlook, since they were demonstrated in randomized clinical trials to benefit patient affected by the related condition FAP-1 otherwise known as transthyretin-related hereditary amyloidosis. Permanent pacing can be employed in cases of symptomatic slow heart rate (bradycardia). Heart failure medications can be used to treat symptoms of difficulty breathing and congestion.
Gene-based therapies for patients with HSAN I are not available to date, hence supportive care is the only treatment available for the patients. Ulcero-mutilating complications are the most serious, prominent, and leading diagnostic features in HSAN I. Since the complications mimic foot ulcers caused by diabetic neuropathy, the treatment for foot ulcers and infections can follow the guidelines given for diabetic foot care which starts with early and accurate counseling of patients about risk factors for developing foot ulcerations. Orthopedic care and the use of well fitting shoes without pressure points should also be included. Recently, the treatment of the foot complications has reached an efficient level allowing treatment on an outpatient basis. Early treatment of the foot complications often avoids hospitalization and, in particular, amputations. In sum, the principles of the treatment are removal of pressure to the ulcers, eradication of infection, and specific protective footwear afterwards.
Often the most important goal for patients with CMT is to maintain movement, muscle strength, and flexibility. Therefore, an interprofessional team approach with occupational therapy, physical therapy, orthotist, podiatrist and or orthopedic surgeon is recommended. PT typically focuses on muscle strength training, muscle, and ligament stretching while OT can provide education on energy conservation strategies and moderate aerobic exercise in activities of daily living. Physical therapy should be involved in designing an exercise program that fits a person's personal strengths and flexibility. Bracing can also be used to correct problems caused by CMT. An orthotist may address gait abnormalities by prescribing the use of ankle-foot orthoses (AFOs). These orthoses help control foot drop and ankle instability and often provide a better sense of balance for patients. Appropriate footwear is also very important for people with CMT, but they often have difficulty finding well-fitting shoes because of their high arched feet and hammer toes. Due to the lack of good sensory reception in the feet, CMT patients may also need to see a podiatrist for help in trimming nails or removing calluses that develop on the pads of the feet. A final decision a patient can make is to have surgery. Using a podiatrist or an orthopedic surgeon, patients can choose to stabilize their feet or correct progressive problems. These procedures include straightening and pinning the toes, lowering the arch, and sometimes, fusing the ankle joint to provide stability. CMT patients must take extra care to avoid falling because fractures take longer to heal in someone with an underlying disease process. Additionally, the resulting inactivity may cause the CMT to worsen.
The Charcot-Marie-Tooth Association classifies the chemotherapy drug vincristine as a "definite high risk" and states that "vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms."
There are also several corrective surgical procedures that can be done to improve physical condition.
Treatment is dependent upon diagnosis and the stage at which the diagnosis is secured. For toxic and nutritional optic neuropathies, the most important course is to remove the offending agent if possible and to replace the missing nutritional elements, orally, intramuscularly, or intravenously. If treatment is delayed, the injury may be irreversible. The course of treatment varies with the congenital forms of these neuropathies. There are some drug treatments that have shown modest success, such as Idebenone used to treat LOHN. Often treatment is relegated to lifestyle alterations and accommodations and supportive measures.
Multifocal motor neuropathy is normally treated by receiving intravenous immunoglobulin (IVIG), which can in many cases be highly effective, or immunosuppressive therapy with cyclophosphamide or rituximab. Steroid treatment (prednisone) and plasmapheresis are no longer considered to be useful treatments; prednisone can exacerbate symptoms. IVIg is the primary treatment, with about 80% of patients responding, usually requiring regular infusions at intervals of 1 week to several months. Other treatments are considered in case of lack of response to IVIg, or sometimes because of the high cost of immunoglobulin. Subcutaneous immunoglobulin is under study as a less invasive, more-convenient alternative to IV delivery.
If patients with HSAN I receive appropriate treatment and counseling, the prognosis is good. Early treatment of foot infections may avoid serious complications. Nevertheless, the complications are manageable, thus allowing an acceptable quality of life. The disease progresses slowly and does not influence the life expectancy if signs and symptoms are properly treated.
There is currently no known pharmacological treatment to hereditary motor and sensory neuropathies. However, the majority of people with these diseases are able to walk and be self-sufficient. Some methods of relief for the disease include physical therapy, stretching, braces, and sometimes orthopedic surgery. Since foot disorders are common with neuropathy disorders precautions must be taken to strengthen these muscles and use preventative care and physical therapy to prevent injury and deformities.
Because different types of myopathies are caused by many different pathways, there is no single treatment for myopathy. Treatments range from treatment of the symptoms to very specific cause-targeting treatments. Drug therapy, physical therapy, bracing for support, surgery, and massage are all current treatments for a variety of myopathies.
There is no standard treatment for LCDD. High-dose melphalan in conjunction with autologous stem cell transplantation has been used in some patients. A regimen of bortezomib and dexamethasone has also been examined.
There are drugs that can increase serum HDL such as niacin or gemfibrozil. While these drugs are useful for patients with hyperlipidemia, Tangier's disease patients do not benefit from these pharmaceutical interventions.
Therefore, the only current treatment modality for Tangier's disease is diet modification. A low-fat diet can reduce some of the symptoms, especially those involving neuropathies.
There have been attempts to control the inflammation using drugs that work in other conditions where inflammation is a problem. The most successful of these are steroids, but they have side effects when used long term. Other medications, including methotrexate, colchicine and canakinumab, have been tried with some success. Otherwise, the treatment is supportive, or aimed solely at controlling symptoms and maximizing function.
Although the FD-causing gene has been identified and it seems to have tissue specific expression, there is no definitive treatment at present.
Treatment of FD remains preventative, symptomatic and supportive. FD does not express itself in a consistent manner. The type and severity of symptoms displayed vary among patients and even at different ages on the same patients. So patients should have specialized individual treatment plans. Medications are used to control vomiting, eye dryness, and blood pressure. There are some commonly needed treatments including:
1. Artificial tears: using eye drops containing artificial tear solutions (methylcellulose)
2. Feeding: Maintenance of adequate nutrition, avoidance of aspiration; thickened formula and different shaped nipples are used for baby.
3. Daily chest physiotherapy (nebulization, bronchodilators, and postural drainage): for Chronic lung disease from recurrent aspiration pneumonia
4. Special drug management of autonomic manifestations such as vomiting: intravenous or rectal diazepam (0.2 mg/kg q3h) and rectal chloral hydrate (30 mg/kg q6h)
5. Protecting the child from injury (coping with decreased taste, temperature and pain perception)
6. Combating orthostatic hypotension: hydration, leg exercise, frequent small meals, a high-salt diet, and drugs such as fludrocortisone.
7. Treatment of orthopedic problems (tibial torsion and spinal curvature)
8. Compensating for labile blood pressures
There is no cure for Familial Dysautonomia.
Currently there is no cure for myotubular or centronuclear myopathies. Treatment often focuses on trying to maximize functional abilities and minimize medical complications, and involvement by physicians specializing in Physical Medicine and Rehabilitation, and by physical therapists and occupational therapists.
Medical management generally involves efforts to prevent pulmonary complications, since lung infections can be fatal in patients lacking the muscle strength necessary to clear secretions via coughing. Medical devices to assist with coughing help patients maintain clear airways, avoiding mucous plugs and avoiding the need for tracheostomy tubes.
Monitoring for scoliosis is also important, since weakness of the trunk muscles can lead to deviations in spinal alignment, with resultant compromise of respiratory function. Many patients with congenital myopathies may eventually require surgical treatment of scoliosis.
Median survival for patients diagnosed with AL amyloidosis was 13 months in the early 1990s, but had improved to c. 40 months a decade later.