Research Summary Sept 2021

Alex - The Leukodystrophy Charity

Adrenoleukodystrophy (ALD)

Childhood cerebral form of adrenoleukodystrophy: short-term effect of bone marrow transplantation on brain magnetic resonance (MR) observations

Bone marrow transplantation can affect brain MR observations in childhood-onset cerebral adrenoleukodystrophy. Although brain MR findings do not typically resolve, they do seem to stabilize, which is an improvement over the natural MR history of the disease.


Treating Leg Symptoms in Women With X-linked Adrenoleukodystrophy

The investigators recently observed that up to 25% of women with X-linked adrenoleukodystrophy (ALD) have moderate to severe Restless Leg Syndrome (RLS). In this study, the investigators aim to estimate the prevalence of RLS among women with ALD and to assess whether pramipexole improves RLS symptoms as well as sleep and gait measures in women with ALD.


Cardiac Tamponade in Adrenoleukodystrophy with Addison’s Disease

Cardiac tamponade is a life-threatening medical emergency and can arise in many clinical situations. They present the case of a 59-year-old man with adrenoleukodystrophy and Addison’s disease who was admitted to the emergency department with severe abdominal pain that turned out to be cardiac tamponade of unknown aetiology. An association between cardiac tamponade and Addison’s disease has been reported in the literature, so this aetiology should be considered in the differential diagnosis for patients presenting with unexplained cardiac tamponade.


Magnetic resonance spectroscopy as marker for neurodegeneration in X-linked adrenoleukodystrophy

X-linked adrenoleukodsytrophy (ALD) is a genetic neuro-metabolic disorder, causing a slowly progressive myelopathy in adult male and female patients. New disease modifying therapies for myelopathy are under development. This calls for new (imaging) markers able to measure disease severity and progression in clinical trials. In this prospective cohort study, they measured cerebral metabolite levels with Magnetic Resonance Spectroscopy (MRS), and evaluated their potential as biomarkers for disease severity and neurodegeneration in ALD. The results imply that cerebral metabolite levels – and more specifically the tNAA/tCr ratio – measured with MRS, have potential value as (imaging) biomarkers in ALD.


Glycosphingolipids with Very Long-Chain Fatty Acids Accumulate in Fibroblasts from Adrenoleukodystrophy Patients

Adrenoleukodystrophy (X-ALD) is an X-linked genetic disorder caused by mutation of the ATP-binding cassette subfamily D member 1 gene, which encodes the peroxisomal membrane protein, adrenoleukodystrophy protein (ALDP). ALDP is associated with the transport of very-long-chain fatty acids (VLCFAs; carbon chain length ≥ 24) into peroxisomes. Defective ALDP leads to the accumulation of saturated VLCFAs in plasma and tissues, which results in damage to myelin and the adrenal glands. Here, they profiled the glycosphingolipid (GSL) species in fibroblasts from X-ALD patients. In conclusion, they precisely quantified SM and various GSLs in fibroblasts from X-ALD patients and determined structural information of the elevated VLCFA-containing GSLs.


Joint research team finds potential therapy for ALD

The joint research team, too, applied gene-editing therapy using gene scissors to patient-derived cells and animal models for the first time to correct mutated genes in ALD patients. Professor Bae’s team used the homology-independent targeted insertion (HITI) method and the adenine base editing (ABE) method to insert the normal ABCD1 gene into the target site in cells collected from ALD patients succeeded in gene editing. Gene editing is a method of correcting a mutated gene that causes disease by replacing a part of the DNA with errors with gene scissors, and ABE replaces one adenine base based on guide RNA. Afterward, Professor Cho’s team tried gene-editing therapy using adeno-associated virus vectors in an ALD animal model. As a result, the team confirmed that ABCD1 mRNA expression increased in the brain, spinal cord, liver, kidney, and adrenal glands while decreasing long-chain fatty acids in the blood

Alex - The Leukodystrophy Charity

Adrenomyeloneuropathy (AMN)

Quality of Life in Women With X-linked Adrenoleukodystrophy (X-ALD_QoL)

The primary objectives of this study are 1) to assess the prevalence of symptomatic courses in female carriers of X-ALD and 2) to determine the impact of AMN symptoms on the quality of life of affected women in various areas (including everyday life, work, social network, sleep quality, sexuality, mood). Participants are asked to fill in self-report questionnaires, which are available in English, German, and French and are provided electronically on the online platform Leuconnect ( launched by European Leukodystrophies Association (ELA) international (


Alex - The Leukodystrophy Charity

Alexander Disease

A Case Report of Adult-Onset Alexander Disease with a Tumor-Like Lesion in the Lateral Ventricle

Adult-onset Alexander disease (AOAD) is an autosomal dominant progressive astrogliopathy caused by pathogenic variants in glial fibrillary acidic protein (GFAP). Individuals with this disorder often present with a typical neuroradiologic pattern, including frontal white matter abnormality with contrast enhancement, atrophy and signal intensity changes of the medulla oblongata and upper cervical cord on MRI. Focal lesions are rarely seen in AOAD, which causes concern for primary malignancies. This study aimed to present the case of a 37-year-old male patient initially diagnosed with an astrocytoma in the lateral ventricle that was later identified as GFAP mutation-confirmed AOAD. GFAP sequencing revealed a heterogeneous missense mutation point c.236G>A. Hence, AOAD should be considered in patients with tumor-like lesion brain lesion in association with atrophy of medulla oblongata and upper cervical spinal cord, and frontal white matter abnormality with contrast enhancement.


Clinical and radiological characteristics of older-adult-onset Alexander disease

The neurological and MRI findings of older-adult-onset ALXDRD patients showed typical features of bulbospinal ALXDRD but their disease progression was more severe than that in younger-adult-onset ALXDRD, and patients developed dependence within 2 years from onset. Cerebral white matter damage tended to progress in proportion to the duration of illness. The case study may help to advance understanding of the clinical spectrum of ALXDRD.


Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalopathy (CADASIL)


Unraveling the role of NOTCH3 dysfunction in disease and for therapy development : a focus on CADASIL

A thesis to increase the understanding of the role of NOTCH3 dysregulation in vascular disease and in the developmental disorder IMF as well as provided important preclinical proof of concept data for novel therapeutic strategies aimed to interfere with the NOTCH3 misfolding and aggregation in CADASIL.

Alex - The Leukodystrophy Charity

Cockayne Syndrome (CS)

Halberd Receives Patent for Treatment of Cockayne Syndrome – May Provide Pathway to Slow Aging

Cockayne Syndrome is a fatal autosomal recessive neurodegenerative disorder which causes premature aging and severely impaired development of the nervous system. Cockayne Syndrome is one of only a few known diseases which cause premature aging. Halberd’s scientific team and patent counsel believe that this is one of the first granted patents which could slow the aging process.

Alex - The Leukodystrophy Charity

GM2 gangliosidosis

Polaryx Therapeutics Announces FDA Grants Orphan Drug Designation for PLX-200 in GM2 Gangliosidoses

Polaryx Therapeutics, Inc. (“Polaryx”), a biotech company developing small molecule therapeutics for lysosomal storage disorders, announced today that the U.S. Food and Drug Administration (“FDA”) has granted Orphan Drug Designation for PLX-200 to treat GM2 gangliosidoses. This designation is one of the important development milestones for the company, because it allows an expanded use of PLX-200 to one of the key lysosomal storage disorders which have clear unmet medical needs. Furthermore, this designation validates the rationale for clinical use of PLX-200 in GM2 gangliosidoses patients.


Novel GM2 gangliosidosis treatment improves symptoms, functioning, QOL

IntraBio Inc. announced positive clinical trial results for IB1001, a pipeline drug intended to treat GM2 gangliosidosis. The multinational clinical trial met its primary endpoint, clinical impression of change in severity (CI-CS), as well as its secondary endpoints, which included patient clinical global impression of change (CGI-C) assessment, according to a press release from the company. IB1001 is the first drug to demonstrate a statistically significant and clinically meaningful effect for the treatment of GM2 gangliosidosis

Alex - The Leukodystrophy Charity

Krabbe Disease

Polaryx Therapeutics Receives FDA Orphan Drug Designation for PLX-200 to Treat Krabbe Disease

Polaryx Therapeutics announced today that the U.S. Food and Drug Administration (“FDA”) has granted Orphan Drug Designation for PLX-200 to treat Krabbe disease. Granting by the FDA of Orphan Drug Designation for PLX-200 in Krabbe disease supports the use of PLX-200 to treat key lysosomal storage disorders with unmet medical needs. Because supportive care is the only available treatment option for most cases of Krabbe disease, this designation validates the scientific rationale and strongly motivates us to expedite the clinical development of PLX-200 in Krabbe disease. They are moving forward with the necessary development steps to move into the clinical study as soon as possible.

Alex - The Leukodystrophy Charity

Metachromatic Leukodystrophy (MLD)

Cure MLD, The Calliope Joy Foundation and NORD Launch A Research and Engagement Study of Metachromatic Leukodystrophy (MLD)

Research study is open to participants worldwide to advance understanding and treatments for Metachromatic Leukodystrophy, a recessive genetic disorder that is characterized by the accumulation of fats (lipids) called sulfatides causing damage to the nervous system. The new study, Metachromatic Leukodystrophy Community United Research and Engagement Survey (MLDCures), creates a platform for patients around the world to share information about Metachromatic Leukodystrophy (MLD). Its purpose is to build an international resource to be used by scientists in future research.

Alex - The Leukodystrophy Charity

Pelizaeus-Merzbacher Disease (PMD)

Scientists discover inherited neurodegenerative disease in monkeys

Scientists have identified a naturally occurring mutation in nonhuman primates that closely resembles a rare neurodegenerative disease in people. The discovery could lead to the development of new therapies to treat Pelizaeus-Merzbacher disease and is the latest in a trove of discoveries made possible by a massive genomic database.

Alex - The Leukodystrophy Charity