Adrenomyeloneuropathy (AMN)

Adrenomyeloneuropathy (AMN) is a form of adrenoleukodystrophy. AMN patients generally have spinal cord dysfunction, which leads to the initial symptoms including difficulties in walking, muscle spasms, peripheral neuropathy (numbness or tingling in the feet and legs), and bladder or bowel symptoms. In the adult onset of the disease, symptoms typically are seen as early as 20 years old and then throughout adulthood. Some men also develop cerebral ALD.

ALD Connect held an FDA Listening Session for AMN in 2021. Click here to read the summary.

Diagnosis

Adrenomyeloneuropathy (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 men with AMN. A DNA-based blood test is also available.

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

Symptoms

The symptoms of AMN can be quite variable. Common symptoms of AMN include stiffness, weakness, and pain in the legs. This starts gradually and can progress over time. The nerves to the bladder, bowel, and sex organs can also be affected in AMN. Mobility can gradually deteriorate to the point where the sufferer eventually loses the ability to walk. Below are some of the symptoms that could be present.

Adrenal insufficiency: decreased levels of adrenaline and cortisol, the hormones important in the control of blood pressure, heart rate, and sexual development and reproduction, occurring in approximately 70% of men with AMN
Ataxia: loss of the ability to coordinate muscle movement
Dysarthria: difficulty in articulating words, caused by impairment of the muscles used in speech
Hypertonia: excessive muscle tone
Pain, numbness, or tingling in the legs
Peripheral neuropathy
Seizures: sudden convulsions/attacks/spasms
Sexual dysfunction, or the inability to obtain or maintain an erection
Spastic paraparesis: gradual, progressive weakness and stiffness of the legs; in AMN this is often specific to the lower limbs
Urinary disturbances or incontinence and bowel urgency or incontinence
Walking and balance problems: general leg weakness and stiffness as well as decreased balance that can progress to difficulty walking (mobility devices such as canes, walkers, and wheelchairs may be needed over time)

Standard of Care

Currently there is no cure for AMN. However, there are some clinical and dietary treatments that patients use 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.

Men with AMN should establish care with a neurologist who can order yearly MRIs to monitor for cerebral ALD.

Clinical Trials

ALD Connect receives many questions about clinical trials for men with AMN.

The National Institutes of Health (NIH) offers many helpful educational and informational resources about clinical trials.

Many of our industry partners have candidates in their pipeline for AMN. We have provided some basic information below. You can visit our Clinical Trials page or reach out directly to the companies to learn more. We also recommend reaching out to your treating physician.

This information is accurate as of June 19, 2023.

SwanBio’s initial drug development candidate, SBT101, aims to treat adrenomyeloneuropathy (AMN) by targeting the disease-causing mutation in the ABCD1 gene. SBT101 incorporates a novel approach using AAV9, a vector for delivery with demonstrated therapeutic value and a growing body of safety data.

Patients can contact SwanBio directly by emailing them at [email protected] or by phone at (267) 417-6356.

ACTIVE, NOT RECRUITING

ClinicalTrials.gov: NCT05008874 Study of Disease Progression in Adults With Inherited Forms of Spastic Paraplegia (CYGNET)

Click here to view the IRB-approved flyer for this study.

RECRUITING

ClinicalTrials.gov: NCT05394064 A Study to Evaluate Administration of SBT101 Gene Therapy in Adult Patients With Adrenomyeloneuropathy (AMN) (PROPEL)

Click here here to view the IRB-approved flyer for this study.

Leriglitazone (MIN-102) is a novel, orally bioavailable and selective PPAR gamma agonist with a potential best-in-class profile indicated for CNS diseases. It is one of the several metabolites of pioglitazone and has a demonstrated sufficient brain penetration and favorable safety profile in humans, allowing PPAR gamma engagement in the CNS above the level that can be safely achieved with pioglitazone and other glitazones. It showed robust preclinical proof-of-concept in animal models of multiple diseases by modulating pathways leading to mitochondrial dysfunction, oxidative stress, neuroinflammation, demyelination and axonal degeneration.

ACTIVE, RECRUITING

ClinicalTrials.gov: NCT05819866 A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adult Male Subjects With Cerebral Adrenoleukodystrophy (CALYX)

CLICK HERE TO APPLY.

ACTIVE, NOT RECRUITING

ClinicalTrials.gov: NCT03231878 A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients

PXL770 is a first-in-class direct AMPK activator. Clinical Phase 1 and 2a development to-date has demonstrated target engagement and translation of several metabolic efficacy parameters to humans which suggests the likelihood of broader translation for this mechanism. PXL770 was observed to ameliorate key features of ALD in preclinical models, including both patient-derived cells and a classical rodent disease model.

Preclinical and clinical results obtained with pioglitazone and a related molecule, leriglitazone (Minoryx), support the potential utility of PXL065 in ALD. PXL065 was observed to ameliorate key features of ALD in preclinical models, including both patient-derived cells and a classical rodent disease model. PXL065 has open IND for ALD in the U.S. PXL065 differentiates from pioglitazone and leriglitazone in several ways including its potential for greater efficacy and reduced side effects.

NOT YET RECRUITING

ClinicalTrials.gov: NCT05200104 Study to Assess PXL065 in Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)

NOT YET RECRUITING

ClinicalTrials.gov: NCT05146284 Study to Assess PXL770 in Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)

Resources

ALD Connect hosts a Community Call for Men with AMN each month. This call is usually on the fourth Tuesday of each month at 7 PM Eastern. Be sure to follow us on social media and subscribe to our newsletter to watch for the announcements. You can also bookmark our Community Calendar, which is where we post the links to register for the Community Calls.

On June 12, 2021, ALD Connect hosted a Bootcamp for Men with AMN. The recordings are below.