Contact/Director UF ALD Clinic
Hans H Shuhaiber M.D.
What is adrenoleukodystrophy?
Adrenoleukodystrophy (ALD) is a rare genetic condition that affects males and females differently. In childhood, boys are primarily affected. Girls are not typically affected, though they may develop symptoms as adults.
ALD is caused by mutations in the ABCD1 gene that prevent the body from breaking down very-long-chain fatty acids (VLCFAs). As a result, VLCFAs build up in the brain, nervous system, and adrenal glands.
What are the types of adrenoleukodystrophy (ALD)?
There are four types of ALD:
1. Childhood cerebral adrenoleukodystrophy (also known as cerebral ALD, CALD, or CCALD)
2. Adrenal insufficiency, also called Addison’s disease
3. Adrenomyeloneuropathy, a form of ALD that affects the spinal cord and nerves, typically in adult men
4. Asymptomatic ALD, which occurs in people who have a mutation in the ABCD1 gene but no symptoms
A person can have more than one type of ALD. Most of the information on this page refers to CALD, the type of ALD that affects the brain during childhood.
What is cerebral adrenoleukodystrophy (CALD)?
Cerebral adrenoleukodystrophy, also known as cerebral ALD or CALD, affects the brain, typically during childhood. It occurs in about 1 in 21,000 boys between ages 4 and 10, affecting about 35 to 40 percent of boys with the ABCD1 mutation. Females with the ABCD1 mutation are highly unlikely to develop CALD. Approximately half may develop neurological symptoms in adulthood, but these typically are due to adrenomyeloneuropathy and spinal cord dysfunction, and are not cerebral.
In CALD, VLCFAs build up in the brain and can destroy the protective myelin sheath around the nerve cells that control our muscles, interfering with their ability to communicate with the brain. Untreated, CALD progresses rapidly and can cause permanent cognitive and motor disabilities and death, usually within four to eight years.
What does the UF ALD Clinic do?
At UF’s ALD Clinic we perform genetic testing for ABCD gene molecular analysis which can help identify mutations that cause diseases such as X-linked adrenoleukodystrophy (ALD). W e perform Three generation genetic pedigree analysis or 3GP, which is a visual representation of a family’s structure that helps healthcare professionals gather and organize data to make clinical decisions based on the results. And we handle screening and enrollment into the CALYX Clinical Study in cALD, if trial requirements are met by patient.
The CALYX Clinical Study in cALD
The CALYX trial is a phase 3, multi-center, randomized (1:1), double-blind, placebo-controlled, clinical study that has been designed to compare the efficacy and safety of leriglitazone with that of placebo in the treatment of cerebral adrenoleukodystrophy (cALD). CALYX will enroll 40 adult male X-ALD patients with progressive cALD defined by the presence of gadolinium-enhancing brain lesions, and where HSCT (haematopoietic stem cell transplantation) is not recommended or refused by the patient. Patients will be randomized either to leriglitazone or placebo with 1:1 randomization. The key exclusion criteria involve a Loes Score greater than 12, and patients that previously received HSCT or gene therapy. The trial has an adaptive duration with an initial efficacy read at 18 months and if needed subsequent efficacy assessments at 27 and 36 months respectively with the option to complete the study at any of the three time points once statistical significance is reached. After completing the randomized phase patients will continue into an open-label extension (OLE). The study was designed with input from FDA, as well as US clinical experts in X-ALD and patient advocacy groups. For further information visit: https://beta.clinicaltrials.gov/study/NCT05819866