Adrenomyeloneuropathy (AMN) is a form of adrenoleukodystrophy that affects adult men. AMN patients generally have spinal cord dysfunction, also known as myelopathy, 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. AMN has an adult onset, and symptoms are typically seen as early as 20 years old and throughout adulthood. Current estimates suggest that around 20% of adult men also develop cerebral ALD.
Adrenomyeloneuropathy (AMN)
Diagnosis
See FAQs for the basics of an ALD diagnosis. Myelopathy related to AMN is typically suspected in an adult with ALD who exhibits symptoms of chronic spinal cord disease.
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 individual may eventually lose the ability to walk. Below are some of the symptoms that could be present. However, it is important to keep in mind that symptoms and rate or progression differ between any two individuals with AMN. One individual may begin using a wheelchair early on, while another will never progress to needing a wheelchair.
- Adrenal insufficiency: inadequate production of hormones by the adrenal glands, occurring in approximately 70% of men with AMN
- Ataxia: loss of the ability to coordinate muscle movement
- Falling or tripping
- Fatigue and sleep disturbances
- Hypertonia: excessive muscle tone
- Peripheral neuropathy: pain, numbness, or tingling in the legs or feet
- Sexual dysfunction, or the inability to obtain or maintain an erection
- Spastic paraparesis: gradual, progressive weakness and stiffness of the legs
- Thinning hair or balding
- 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 or an unusual gait (mobility devices such as canes, walkers, and wheelchairs may be needed over time)
Standard of Care
Currently there is no cure for AMN. Apart from the manifestation of adrenal insufficiency, current treatments aim to alleviate some of the symptoms of the disease. Symptom management can include medications to improve spasticity issues and bowel and bladder dysfunction. Many patients also undergo regular physical and/or occupational therapy. Work with your care team to find a treatment plan that works for you. Men with AMN who have adrenal insufficiency should receive daily steroid replacement therapy, as failure to test for and treat adrenal insufficiency can lead to a fatal outcome.
Monitoring is very important for men with AMN. According to current standard of care guidelines, men with AMN should establish care with a neurologist who can order yearly MRIs to monitor for cerebral ALD, which is more easily treated when caught early. Men should also establish care with an endocrinologist, whether or not they are known to have adrenal insufficiency. Men with adrenal insufficiency should follow with their endocrinologist to monitor their care, and men without adrenal insufficiency should be monitored for the development of adrenal insufficiency yearly. Men should be aware of the symptoms of adrenal insufficiency, and should seek care right away if they begin to develop these symptoms.
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.
Click here to view the CALYX leaflet.
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. ALD Connect also hosts a peer mentor program, which connects less experienced community members to more experienced members of a similar phenotypes. You can apply for a peer mentor here.
On May 7, 2021, ALD Connect hosted a Listening Session with the FDA regarding Men with AMN. Read the summary here. On July 22, 2022, ALD Connect hosted an Externally-Led Patient-Focused Drug Development Meeting to educate the FDA on adult manifestations of ALD, including AMN and adult cerebral ALD. View the recording and our resulting Voice of the Patient Report here. On June 12, 2021, ALD Connect hosted a Bootcamp for Men with AMN. The recordings are below.
Standards of Care
Dr. Florian Eichler
Dr. Brian Wishart
Cerebral ALD
Dr. Troy Lund
Aaron Gardner
Embarrassing Symptoms
Dr. Pablo Gomery
Camille Corre
Tim Maguire
Looking Ahead: Industry Pipeline
Ben Lenail
Uwe Meya
Asif Paker
Rohan Gandhi
David Moller