Adrenomyeloneuropathy (AMN)

Adrenomyeloneuropathy (AMN)

Adrenomyeloneuropathy (AMN) is a genetic neuro-degenerative disease. It is the adult onset of adrenoleukodystrophy (ALD). In about half of the boys who inherit the mutated ALD gene, symptoms of the disease do not develop until young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap.

In approximately one third of AMN patients, the central nervous system can also become involved. These AMN patients undergo the same mental and physical deterioration as boys with the childhood form of the disease, adrenoleukodystrophy (ALD). The progression of the disease is slower, usually declining to a vegetative state and/or death.

There is no effective treatment for the adult onset of ALD, which is commonly referred to as adrenomyeloneuropathy (AMN); rather, medication and therapies are employed in a palliative manner.

Diagnosis

AMN can be diagnosed by a simple blood test that analyzes the amount of very long chain fatty acids; the levels of these molecules are elevated in X-ALD (see our general fact sheet on X-ALD). A DNA-based blood test is also available.

If the blood test suggests X-ALD, then generally an MRI will be performed in order to assess cerebral involvement. Additionally, the patient will be evaluated for adrenal insufficiency (by another blood test), as this is a common symptom of the disease that can be corrected.

Symptoms

Like all of the categories of X-ALD, the symptoms of AMN can be quite variable. Below we have listed some of the symptoms that could be present, along with definitions as necessary.

  • Difficulty in walking/change in walking pattern: this is the most common initial symptom of patients with AMN
  • Spastic paraparesis: gradual, progressive weakness and stiffness of the legs; in AMN this is often specific to the lower limbs
  • Ataxia: loss of the ability to coordinate muscle movement
  • Hypertonia: excessive muscle tone
  • Visual defects
  • Dysarthria: Difficulty in articulating words, caused by impairment of the muscles used in speech
  • Seizures: sudden convulsions/attacks/spasms
  • Adrenal insufficiency: The adrenal glands are located above the kidneys, and are responsible for releasing certain hormones such as adrenaline and cortisol. These hormones are important in the control of blood pressure, heart rate, and sexual development and reproduction. In adrenal insufficiency, these hormones are not produced at the appropriate levels and so these processes are not properly controlled. Adrenal insufficiency occurs in approximately 70% of men with AMN.
  • Sexual dysfunction/impotence – This may be related either to involvement of the spinal cord or the testes themselves. The latter is relatively uncommon. It can be diagnosed by measuring testosterone levels in plasma.
  • Behavioral changes
  • Bladder dysfunction
  • Mild peripheral neuropathy
  • Weight loss
  • Nausea
Treatment

Currently there is no cure for AMN; however, there are some clinical and dietary treatments that patients are using to help alleviate some of the symptoms of the disease.

One of the possible symptoms of patients with AMN is adrenal insufficiency. The adrenal glands are located above the kidneys, and are responsible for releasing certain hormones such as adrenaline and cortisol. These hormones are important in the control of blood pressure, heart rate, and sexual development and reproduction. In adrenal insufficiency, these hormones are not produced at the appropriate levels and so these processes are not properly controlled. Adrenal insufficiency can be corrected by steroid replacement therapy, which generally will improve the quality of life of the patient. Failure to test for and treat adrenal insufficiency can lead to a fatal outcome. Only replacement dosage of steroids, which do not cause the side effects of “pharmacologic” doses, are required.

One biotechnology company working to develop a treatment for AMN is ReceptoPharm, Inc., a subsidiary of Nutra Pharma Corporation. This treatment just completed its Phase IIb/IIIa clinical trial in London, England. To learn more about ReceptoPharm, please click here.

New Therapies
  • Ampyra: a K+ blocker, is said to improve nerve conduction, no published data exists for ALD or AMN.  Approved for Multiple Sclerosis.
  • MD 1003: an anti-oxidant, is energy producing in neurons and may repair myelin.
  • EPI-743: an anti-oxidant, shown to reduce oxidative stress in vitro. An AMN trial is close to being initiated in Italy. Contact Dr. Keith Van Haren kpv@stanford.edu
  • Natalizumub: an anti-integrin, known to block lymphocyte infiltration in central nervous system. Approved for Multiple Sclerosis.
  • AAV: an in vivo gene therapy treatment shown to lower VLCFAs.
  • Sobiterome: a thyroid agonist that up regulates ABCD2. Clinical study under design.
Women Carriers

For many years X-ALD has been regarded as a disease that only affects boys and men. However, over the last 15 years it has become clear that at least 20 to 50% of all female carriers develop neurological symptoms as well. Only very rarely female carriers develop deficient function of the adrenal glands.

Resources:


ALD Connect

Their mission is to improve health outcomes for patients with ALD and AMN by empowering patients, raising awareness, and accelerating the translation of scientific advances into better clinical care.

AMN Easier

AMN EASIER provides information and support to men and women with adrenomyeloneuropathy (AMN)

  • Answers to health questions from AMN patient experts
  • Lets you see what other AMN patients are doing and thinking
  • Opens up ideas and possibilities for therapies that could help


AMN Help

We invite you to review this site to learn more about AMN, how it is diagnosed, and what treatments options are currently available.
On this site, you will have the opportunity to:

  • Learn about Adrenomyeloneuropathy (AMN)
  • Explore current diagnosis procedures
  • Discover treatment options