Optimizing Treatment for Cerebral Adrenoleukodystrophy in The Era of Gene Therapy

DEFINITION

• Adrenoleukodystrophy (ALD) is one of a group of genetic disorders called the leukodystrophies that cause damage to the myelin sheath, an insulating membrane that surrounds nerve cells in the brain.
• Adrenoleukodystrophy is linked to the X-chromosome, and is thus more prevalent in males, as females can only have the disease if both of their X-chromosomes are affected. It is a sex-linked trait.
• Also known as X-ALD

What is ALD? cont.

• People with ALD accumulate high levels of saturated, very long chain fatty acids (VLCFA) in the brain and adrenal cortex.
• 1 per 20,000 people suffer from X-ALD
• ALD affects all ethnic groups
• Girls with ALD may have milder symptoms

Symptoms

• Severe mood swings
• Memory loss
• Seizures
• Progressive dementia
• Fatigue
• Eventually death

Optimizing Treatment for Cerebral Adrenoleukodystrophy in The Era of Gene Therapy

Applications in Medicine

Disease progression, which leads to loss of neurologic function and death, can be halted only with allogeneic hematopoietic stem-cell transplantation

Impact

• ALD can cause the patient, his/her family, and society to suffer.
• ALD is particularly disturbing as it can cause some personality changes, i.e. mood swings.

PROS

• It was established that stabilization of cerebral adrenoleukodystrophy lesions may occur 6 to 12 months after successful allogeneic hematopoietic stem-cell transplantation, and this is currently the only effective treatment

Joselyne Defás Molina

IN ECUADOR

CONS

• In the study 2 patients had neurologic disease progression:
• One withdrew from the study and died later from complications of allogenic transplantation.
• In the other patient, neurologic functions deteriorated rapidly after treatment.

• The infantile cerebral form of the disease affects 48% of patients with the biochemical defect of this disease. The adrenomyeloneuropathy (AMN) or adult form of the disease, less frequent than the previous one, affects 25% of the patients.

Works Cited

"NINDS Adrenoleukodystrophy Information Page." Adrenoleukodystrophy Information Page: National Institute of Neurological Disorders and Stroke (NINDS). National Institute of Neurological Disorders and Stroke. Web. 6 Feb. 2015. <http://www.ninds.nih.gov/disorders/adrenoleukodystrophy/adrenoleukodystrophy.htm>.

Steinberg, Steven. X-Linked Adrenoleukodystrophy. U.S. National Library of Medicine. Web. 6 Feb. 2015. <http://www.ncbi.nlm.nih.gov/books/NBK1315/>.

"Genes and Mapped Phenotypes." National Center for Biotechnology Information. U.S. National Library of Medicine. Web. 24 Feb. 2015. <http://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=215>.

“X-Linked Adrenoleukodystrophy." Biocimica Et Biophysica Acta 1763.12 (2006): 1721-732. Print.

"Hematopoietic Stem Cell Transplantation and Hematopoietic Stem Cell Gene Therapy in X-Linked Adrenoleukodystrophy." - Cartier. Web. 24 Feb. 2015. <http://onlinelibrary.wiley.com/doi/10.1111/j.1750-3639.2010.00394.x/full>.

CONCLUSION

• In this study, Lenti-D gene therapy seemed to be a safe and effective therapy.
• Nevertheless, more prolonged follow-up is necessary to assess biologic and clinical response and safety of this treatment.
• If Lenti-D is shown to be a safe and beneficial treatment option for cerebral adrenoleukodystrophy, it may become one of the first gene therapies approved by the Food and Drug Administration for clinical application.

Lorenzo's Oil

• A mixture of oleic acid and erucic acid, known as "Lorenzo's Oil," administered to boys with ALD can prevent or delay symptoms
• Lorenzo’s Oil reduces the fatty acid level, but does not help with symptomatic patients or with adrenal dysfunction

A trailer of the 1992 movie "Lorenzo's Oil" about a child going through the fight of ALD